Development and Optimization of Eudragit® L100 Film for Ocular Delivery of Prednisolone for Dry Eye

Development and Optimization of Eudragit® L100 Film for Ocular Delivery of Prednisolone for Dry Eye | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Development and Optimization of Eudragit® L100 Film for Ocular Delivery of Prednisolone for Dry Eye Vindhya Pal, Sushma Verma, Prashant Verma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7283794/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: One of the more prevalent ocular conditions, dry eye causes between 30 to 40 million individuals in the United States on its own and is a serious human medical issue. Ocular films of prednisolone were developed using a variety of polymeric methods to improve drug accumulation; these films showed benefits such as easier delivery and longer interaction times. Objective: The major purpose of the current research focuses on the creation and optimization of ocular films of prednisolone for the management of dry eye to maximize the therapeutic impact by prolonged interaction at the corneal surface. Method: The current study sought to formulate ocular Films of Prednisolone for treating of dry eye utilizing solvent casting method. The concentration of Polyvinyl pyrrolidone K-30 and Glycerine used as polymer and plasticizer, respectively, in the ocular films were optimized using the central composite design (CCD). Thickness, pH and drug release parameters were adopted as dependent responses. Ocular films were assessed for different physicochemical parameters like film thickness, folding endurance, surface pH, uniformity of weight, drug content, swelling index, moisture adsorption, moisture loss, in-vitro release study, kinetic study, stability study and test of ocular irritation on rabbit eye. Results: The optimized ocular film (P2) with thickness 0.506 mm and pH 6.8 showed appropriate physicochemical characteristics for ocular delivery. The optimized formulation released 90.75% of the encapsulated drug during 12 h. Release followed Higuchi kinetics and revealed transport mechanism was non-fickain. Tests for stability were conducted on this improved formulation. The ocular film passed the sterility test, and the physicochemical characteristics did not significantly alter between the 0th and 60th day. Thus, it was discovered that the formulation was stable. The films did not cause ocular toxicity or irritation, according to the results of the eye irritancy test. Conclusion: Our research leads us to the conclusion that optimized prednisolone ocular film (P2) may help alleviate dry eye by increasing residence duration, prolonging drug release, and requiring less frequent administration. Dry Eye Prednisolone Ocular Delivery Optimization Central Composite Design Kinetic Study Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 1. INTRODUCTION The eye is a sensory organ, establish the sense of sight through tear film turnover and blinking and it protect from external harmful stimuli [ 1 , 2 ]. It involves complex defense mechanism along with continuous elimination of lachrymal fluid. The persistent drain of lacrimal fluid halt ocular retention and intraocular penetration of the drug in several ocular ailments such dry eyes, conjunctivitis, etc. [ 3 ]. One of the most prevalent ocular conditions, dry eye affects between 30 to 40 million individuals in the US alone and is a serious public health problem [ 4 ]. It is associated with corneal surface epithelial illness, lighting sensibility, impaired vision, and eye discomfort [ 5 , 6 ]. Furthermore, it serves as one of the main reasons for clinical examinations, and about 30% of patients claim to have mild or chronic dry eye symptoms [ 7 , 8 ]. Autoimmunity [ 9 , 10 ], hormonal imbalance [ 11 , 12 ], systemic disorders [ 13 – 15 ], genetic diseases [ 16 ], nerve injury [ 17 – 18 ], and gut dysbiosis [ 19 – 21 ] are examples of situations that are considered intrinsic factors. Dry eye can be made worse by a continuous increase in visually demanding computer screen work and contact lens use [ 22 ]. Numerous of these causal variables have a negative effect on either or both of the meibomian glands, the eye surface, the lacrimal glands, and the accompanying network of neurons, which are components of the lacrimal functioning unit [ 23 ]. Artificial tear drops, which hydrate and lubricate the eye, have no pharmacologic action, and only offer transient relief, are the main treatment for mild dry eye [ 24 ]. Inflammation linked to chronic dry eye frequently reacts topically to corticosteroids and cyclosporine-A eye drops [ 25 ]. An artificial glucocorticoid made from cortisol is called prednisolone. As a model drugs in the current study, prednisolone acetate or sodium phosphate are used as ophthalmic suspensions in eye drops to lessen allergic responses that affect the eye and to ease the associated symptoms including redness, swelling, and itching of the eye [ 26 , 27 ]. Prednisolone reduces inflammation by reversing the treatment's increased capillary permeability and inhibiting polymorphonuclear leukocyte movement [ 28 ]. In the current study, Prednisolone ocular films were created by combining Polyvinyl pyrrolidone K-30 using glycerine in various proportions to lengthen the pre-corneal occupancy period and reduce the duration of medication application. This research project aims to produce an ocular film using the solvent casting process. Using a two-factor and five-level Central Composite Design, the formulation was adjusted with respect to Polyvinyl pyrrolidone K-30, glycerin, thickness, pH, and drug release in 12 hours. For in-vivo ocular irritation in albino rabbits, the most effective formulation was investigated. 2. MATERIALS AND METHODS 2.1. Materials Prednisolone was collected from Central Drug House (P) Ltd., Delhi, India. The following excipients were purchased from Central Drug House (P) Ltd., Delhi, India: Eudragit® L 100, Polyvinyl Pyrrolidone K-30(PVP K-30) and Glycerine. Analytical grade substances and solvents were utilized in the formulation. 2.2. Methods 2.2.1. Experimental design The impact of independent variables, polyvinyl pyrrolidone K-30 and glycerine, on three response variables—thickness, drug release, and pH were examined using a two-factor Central Composite Design. Using Design Expert® software version 13 (Stat-Ease Software), an overall number of nine experiments originated from CCD. One replication of each of the four axial, four factorial, and one center point were included in the randomized sequence of the experiment. Regression analysis on the response surface was used to examine the data. The model selection depended on the Design Expert software's significant terms (p < 0.05), least significant lack of fit, coefficient of variance, and multiple correlation coefficients [ 29 ]. Following that, the desirability function was used to guide the chosen formula selection, enabling simultaneous analysis of every answer. It was chosen to go with a proposal having the lowest thickness and pH and the maximum percentage of medication release. Table 4 shows that the option exhibiting the greatest desirability (nearly one) had been chosen. The chosen formula had been further explained [ 30 ]. The coded and actual values of the independent variables from the optimization procedure are displayed in Table 1 . Table 1 Coded and Actual value of the optimized formulations. Formulations Coded Value Actual Value Polyvinyl Pyrrolidone K-30 (mg) Glycerine (mL) Polyvinyl Pyrrolidone K-30 (mg) Glycerine (mL) P1 -1 + 1 400 3 P2 + 1 -1 600 1 P3 +α 0 641.42 2 P4 0 +α 500 3.42 P5 0 0 500 2 P6 -1 -1 400 1 P7 0 -α 500 0.59 P8 -α 0 358.6 2 P9 + 1 + 1 600 3 Variables: - +α = maximum; -α = minimum; +1 = high; -1 = low; 0 = Mean 2.2.2. Method of preparation of Ocular films The ocular film was prepared using the solvent casting method. To generate a homogenous dispersion, predetermined polymers were combined with 30 ml of solvent and swirled for two hours. subsequently measured quantities of Prednisolone were included and agitated for another two hours using a magnetic stirrer. A sufficient quantity of glycerine was put in and thoroughly blended. The final product was cast onto the petri dish. The films undergo drying at room temperature for 48 hours, and then they are sliced utilising a cork borer, sealed with aluminium foil, and kept for more study. The mixture of the multiple batches is displayed in Table 2 [ 31 ]. Table 2 Formulations of Ocular films loaded with Prednisolone Ingredients Batches P1 P2 P3 P4 P5 P6 P7 P8 P9 Prednisolone (mg) 50 50 50 50 50 50 50 50 50 Eudragit® L100 (mg) 600 600 600 600 600 600 600 600 600 Polyvinyl Pyrrolidone K-30 (mg) 400 600 641.4 500 500 400 500 358.6 600 Glycerine (mL) 3 1 2 3.41 2 1 0.585 2 3 Distilled water (mL) q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s. q.s = sufficient quantity; mg = milligram; mL = milliliter 2.2.3. Thickness measurement Vernier calliper was employed to examine the thickness of the ocular film and record the mean of the measurements [ 32 ]. 2.2.4. Folding endurance By hand folding Prednisolone ocular film repeatedly at the same spot until it cracked or started to show indications of breaking was carried out for measuring folding endurance. The folding endurance score is based on the number of instances the film can be rolled in the same location without shattering [ 33 , 34 ]. 2.2.5. Surface pH Prednisolone ocular film allowed to swell for 30 minutes in a closed Petri dish with 1 ml of distilled water. The expended film had been removed, and the solution's pH level had been measured utilizing a digital pH metre [ 35 ]. 2.2.6. Drug content Three films were obtained from each batch of the formulation to verify that the medication was uniformly distributed across the ocular film. Each film was placed within a glass vail that held 10 ml of STF. With the help of a magnetic stirrer, the film disappeared and the resulting solution got filtered. 1 ml of the filtrate got separated and mixed with 10 ml of purified water. The absorbance had been assessed utilizing UV spectroscopy at 242 nm [ 36 ]. 2.2.7. Weight uniformity To ensure consistent weight, five films had been selected from each batch (n) and separately weighed on a digital scale. The ocular film's average weight was noted [ 37 , 38 ]. 2.2.8. Swelling index The swelling test has been employed to investigate the effects of polymer hydration and bulk hydrophilicity on the release of medications through polymeric matrix. To quantify the swelling of polymeric films, the films were measured and then placed on a Petri dish with Saline tear fluid (STF) maintained at 32 ± 0.5 ºC and pH 7.4. The films were removed out at predetermined intervals of up to 60 minutes, weighed, and finally put reverse into the same container. Utilizing the following equation, the amount of solvent absorption was estimated as the swelling index [ 39 – 41 ]. Swelling index ═ [Wt – W0/ W0] X 100------- (1) Where, W0 is the initial weight of the sample and Wt its weight at time at time t. 2.2.9. % Moisture Absorption The % moisture absorption analysis has been evaluated the film's stability or structural strength in humid conditions. The films were weighed before being put in a desiccator with 100 ml of overexposed sodium chloride solution. After three days, the films were removed and weighed once more [ 42 , 43 ]. The following formula used to determine the percentage of moisture absorption: % Moisture Absorption = Final weight – Initial weight/ Initial weight X 100 2.2.10. % Moisture Loss This test was done to make sure the ocular films were intact when they were dry. The ocular implants were precisely weighed and stored in a dehydrated calcium chloride-filled desiccator. After three days, the films were removed, weighed, and the % moisture loss was determined utilizing a formula: [ 44 , 45 ]. % Moisture Loss = Initial weight – Final weight/ Initial weight X 100 2.2.11. In-vitro drug release study The traditional standard cylindrical tube made in the lab was used to perform the in-vitro permeation of medication taken from different ocular film. A simple modification of open ended glass tube was used. The open tube's end, which served as the donor compartment, had the diffusion cell membrane attached to it. This compartment contained an ocular film. The membrane of the diffusion cell served as the corneal epithelium. The receptor compartment, which contained 80 ml of STF in a 100 ml beaker, was in directly contact with the whole surface of the membrane. The contents of the receptor compartment seemed continuously mixed with a magnetic stirrer during the temperature continued to stay at 37 ± 0.5 ºC. At predefined intervals, 5 ml of the receptor compartment medium was taken out for completely fresh STF. Following the necessary dilutions against the reference and the use of STF as a blank, the aliquots were examined for the presence of the medication utilizing a UV-Visible Spectrophotometer (Pharmaspec 1700, Shimadzu, Japan) at 242 nm [ 46 ]. 2.2.12. Kinetic Release Study Several kinetic models were employed to characterize the release kinetics in order to interpret the in vitro drug release data [ 47 ]. Zero-order The zero order rate Eq. (1) explains the systems where the rate of drug release rises with time. C = k 0 t (1) where, C is the concentration of drug at time t, t is the time and k0 is zero-order rate constant expressed in units of concentration/time. First-order The first order Eq. (2) explains the release from the system where rate of drug release is concentration dependent. Log C 0 − Log C = k 1 t/2.303 (2) where, C 0 is the initial concentration of drug and k 1 is the first order rate constant. Higuchi diffusion model Higuchi described the release of drugs from the ocular film as a square root of time dependent process based on Fickian diffusion Eq. (3). C = K H √ t (3) where, K H is the constant reflecting the design variables of the system. Korsmeyer-Peppas Korsmeyer et al. derived a simple mathematical relationship which described the drug release from a polymeric system Eq. (4). M t / M ∞ = K KP t n (4) where M t /M ∞ is the fraction of drug released at time t, K KP is the rate constant and n are the release exponent. 2.2.13. Stability study Accelerated stability observations can be used to estimate how the films' self-life is generated. In the current experiment, films from particular batches were chosen and tightly packed in amber-colored decanters that had been stopped and ploughed with cotton. For six months, they were put under 40°C/75% RH stress storage conditions. At specified intervals, the films were put in 5ml of STF and rotate in a rotary shaking mixer (50rpm). Using a 0.45 µ filter, the solution was cleared after 24 hours. After properly diluting the filtrate with STF, the absorbance was restricted to 242 nm [ 48 ]. 2.2.14. In-vivo study (Eye irritancy study) AIIMS (All India Institute of Medical Sciences), New Delhi-110029's Central Animal Facility, Ansari Nagar, granted permission for the study's use of animals. The approval number for animal ethics is IAEC/NIET/2022/02/46. The in vivo ocular irritation test was performed on either sexed, 2.8 to 4.1 kg New Zealand rabbits. Free leg and eye movement had been allowed. The Draize test has been employed to evaluate eye discomfort. The measurements made using a scoring method proved that the generated ocular films in rabbit eyes were safe. Three animals made up the control group and six animals made up the groups participating in the experiment. Animals in the control group got saline solution in both eyes. All of the animals in the experimentation groups had the films placed in both eyes. For five days, this was done once every 24 hours [ 49 ]. Table 3 Ocular safety test using the Draize irritancy scale. Eye tissue Grading system Calculations Total Cornea: Opacity (O) 0,1,2,3,4 O×A×5 80 Area involved (A) 0,1,2,3,4 Iris: Values for congestion and hemorrhage (I) 0, 1, 2 I×5 10 Conjunctiva: Redness (R) 0, 1, 2,3 Chemosis (C) 0,1,2,3,4 (R + C + D) ×2 20 Discharge (D) 0, 1, 2,3 Total Maximum 110 Note: Scores of 0 and 4 indicate severe conditions for O, R, C, and D, respectively. A corneal coverage scores of 1, 2, 3, or 4 indicates how much of the cornea is protected. Scores between 0 and 2 indicate severity in the case of I. Table 4 Chart for safety evaluation. Scores Assessing 0.0–0.5 0.5–2.5 2.5–15.0 15.0–25.0 25.0–50.0 50.0–80.0 80.0–110.0 Not irritable Virtually not irritable Minimally irritable Mildly irritable Moderately irritable Severely irritable Extremely irritable 3. RESULTS 3.1. Formulation of Prednisolone loaded ocular films The transparent and flexible films would be produced by concentration of Eudragit® L 100, Polyvinyl Pyrrolidone K-30(PVP K-30) and Glycerine. Eudragit® L 100 and Polyvinyl Pyrrolidone K-30 were included as polymer, while Glycerine served as a consistent plasticizer agent. The glycerine concentration of notably affected the flexibility of the ocular films. Figure 1 shown the formulation of Prednisolone loaded ocular films. 3.2. Data analysis, statistical optimization and validation The impact of formulation factors on thickness, percent drug release, and pH was investigated in a total of nine studies. Table 5 contains the response data for every experiment. Table 5 Experimental runs, independent variables, and measured responses of prednisolone ocular films. Run Factor A Factor B Response (R 1 ) Response (R 2 ) Response (R 3) 1 400 3 0.243 ± 0.001 76.61 ± 0.026 7.4 ± 0.058 2 600 2 0.506 ± 0.0005 90.75 ± 0.010 6.8 ± 0.1 3 641.421 1 0.568 ± 0.0005 91.25 ± 0.006 6.7 ± 0.12 4 500 3.41421 0.456 ± 0.01 80.64 ± 0.010 7.1 ± 0.2 5 500 2 0.413 ± 0.001 86.60 ± 0.025 7.2 ± 0.058 6 400 1 0.271 ± 0.002 78.53 ± 0.023 7.4 ± 0.1 7 500 0.585786 0.428 ± 0.001 82.61 ± 0.011 7.5 ± 0.1 8 358.579 2 0.178 ± 0.001 71.35 ± 0.017 7.6 ± 0.2 9 600 3 0.567 ± 0.002 88.72 ± 0.008 6.9 ± 0.153 Note: Factor A : Polyvinyl pyrrolidone K-30 (mg); Factor B : Glycerine (ml); R 1 : Thickness (mm); R 2 : % Drug release; R 3 : pH. The value of responses R 1 (Thickness), R 2 (% Drug release) and R 3 (pH) ranges from 0.178 to 0.568 mm, 71.35 to 91.25% and 6.8 to 7.6 respectively. The best-fitting model recommended by the software was linear for R2 and R3, and quadratic for R1. The recommended models proved to be relevant for functional variables by the results of ANOVA and regression analysis, since each model has a probability value less than 0.05 (Table 6 ). Table 6 Summary of results of regression analysis and ANOVA for measured responses. Responses Model R 2 Adjusted R 2 Predicted R 2 SS DF MS F value P value Model significance R 1 Quadratic 0.9984 0.9959 (NA) 1 0.1620 5 0.0324 385.68 0.0002 Significant R 2 Linear 0.9303 0.9071 0.8699 349.85 2 174.92 40.04 0.0003 Significant R 3 Linear 0.8747 0.8330 0.6938 0.7309 2 0.3654 20.95 0.0020 Significant R 1 : Thickness; R 2 : % Drug release; R 3 : %pH; SS : Sum of Square; DF : Degree of freedom; MS : mean square The relevant polynomial equations for the dependent variable were recommended by software; R 1 = + 0.4130 + 0.1390A + 0.0091B + 0.0222AB – 0.0225A 2 + 0.0117B 2 (5) R 2 = + 83.01 + 6.56A – 0.8420B (6) R 3 = + 7.18–0.2966A – 0.0582B (7) From Eq. 5, it is clear that variables A and B have a positive influence, meaning that thickness grows in tandem with rises in PVP K-30 proportion and glycerine level. The entire impact of A and B on thickness is positive, although the exponentially increasing form of A and B also has a positive influence on thickness. Drug release percentage was positively and negatively impacted by factors A and B (Eq. 6). Thus, drug release rises with polymer concentration whereas drug release percentage decreases with increasing glycerine concentration. A and B had a negative effect on pH. Thickness, Drug release, and pH are depicted in surface contour plots and 3D response surface plots, respectively, in Figs. 2(a) & (b), 3 (a) & (b), and 4 (a) & (b), which were generated from the experimental design. The optimal ocular film was chosen by applying a desirability search strategy. The optimized batch selected based on a formulation with reduced thickness, a medication release percentage of above 85%, a suitable pH, and less negatively potential. Furthermore, the potential influence on medication release was taken consideration while choosing the optimal batch. Numerous investigations have already demonstrated that medication release rises with the quantity of polymers. The batch that considered optimal was batch P2, which included 600 mg of PVP K-30 and 1 ml of glycerine with a desirability close to 1. 3.3. Thickness measurements The films ranged in thickness from 0.178 ± 0.001 to 0.568 ± 0.0005 mm. Table 7 & Fig. 5 presents the findings. It shows that the manufactured prednisolone ocular films had a consistent thickness, that is discovered to be closely correlated with the polymer content. 3.4. Folding Endurance Breaking strength and endurance were used to test the folding endurance of the prednisolone ocular film. This is the maximum number of times the film might be folded in one spot before breaking or showing signs of breaking. The folding endurance of the several formulations of prednisolone ocular films (P1 to P9) was determined to range between 185 ± 1.73 and 209 ± 2.64. This outcome demonstrates that the ocular implant has sufficient strength to resist handling shock. Table 7 provides the corresponding outcomes. 3.5. Surface pH Ocular films are compatible with lachrymal fluids, as indicated by the pH values on the surface of all the films, which ranged from 6.8 ± 0.1 to 7.6 ± 0.2. Table 7 & Fig. 6 shows each of these values. 3.6. Drug content Table 7 shows that the produced ocular films had a drug content value ranging from 99.90 ± 0.002 to 99.99 ± 0.019%. This suggests that the medication was evenly dispersed throughout the polymeric matrix along with the preparation technique used produced the desired outcomes. 3.7. Weight uniformity Table 7 shows that the weights of the ocular films ranged from 51.46 ± 2.23 to 69 ± 4.18 mg. A proper dispersion of the medicine in the polymer and plasticizer is shown by the homogeneity of the weights of the films. 3.8. Swelling index In order to assess the hydrophilicity, hydration, and erosion of the films, the swelling capacity were examined. The pace at which fluid permeates the polymer matrix, the matrix's resistance to water molecules moving through it, and the matrix's final degradation all affect how much swelling results. The results show that all of the formulations generate reduced pain, with swelling index values ranging from 39.4%±0.65 to 72.21%±3.21 in 60 minutes. Table 7 & Fig. 7 represents the results of each formulation. 3.9. % Moisture absorption For each of the nine formulations, the percentage moisture absorption has been determined in triple. The results showed that because PVP polymers are hydrophilic, they had a greater absorption of moisture in the film comprising them. The percentage of moisture absorbed ranged from 3.95 ± 0.7 to 5.79 ± 1.05, indicating that there was no deterioration in durability under highly humid circumstances. Table 7 shows all of the results. 3.10. % Moisture loss There was no difference in the films' dependability as the moisture content decreased. The percentage of moisture loss increased from 6.17 ± 0.5 to 9.61 ± 0.6, indicating that the reliability remained unchanged in dry circumstances. Table 7 presents the findings. Table 7 Physical evaluations of prednisolone ocular films. Formulations Thickness (mm) ± SD Folding endurance (No. of folds) ± SD Surface pH ± SD Drug content (%) ± SD Weight uniformity (mg) ± SD Swelling index (%) ± SD %Moisture absorption ± SD %Moisture loss ± SD P1 0.243 ± 0.001 198 ± 1.73 7.4 ± 0.058 99.96 ± 0.008 51.46 ± 2.23 72.21 ± 3.21 4.63 ± 1.65 8.87 ± 1.03 P2 0.506 ± 0.0005 191 ± 2 6.8 ± 0.1 99.93 ± 0.005 54.12 ± 3.02 69.9 ± 4.29 5.79 ± 1.05 8.96 ± 0.46 P3 0.568 ± 0.0005 194 ± 2.64 6.7 ± 0.12 99.99 ± 0.018 56.1 ± 5.57 50.7 ± 0.72 4.22 ± 0.3 6.17 ± 0.5 P4 0.456 ± 0.01 185 ± 1.73 7.1 ± 0.2 99.95 ± 0.010 53.1 ± 4.39 51.1 ± 3.87 5.27 ± 0.3 8.94 ± 0.5 P5 0.413 ± 0.001 201 ± 2.64 7.2 ± 0.058 99.99 ± 0.019 56.1 ± 4.15 45.0 ± 2.91 5.29 ± 1.7 8.91 ± 0.15 P6 0.271 ± 0.002 203 ± 3.60 7.4 ± 0.1 99.99 ± 0.002 55.1 ± 4.87 48.7 ± 0.25 3.95 ± 0.7 8.55 ± 0.7 P7 0.428 ± 0.001 198 ± 1 7.5 ± 0.1 99.97 ± 0.003 69 ± 4.18 42.2 ± 0.62 4.75 ± 0.34 8.46 ± 0.7 P8 0.178 ± 0.001 205 ± 5.56 7.6 ± 0.2 99.94 ± 0.006 58.4 ± 4.99 39.4 ± 0.65 5.64 ± 1.7 9.61 ± 0.6 P9 0.567 ± 0.002 209 ± 2.64 6.9 ± 0.153 99.90 ± 0.01 56.87 ± 4.06 65.5 ± 0.3.16 5.44 ± 5.4 8.48 ± 2.4 (All values in mean ± S; n = 3) 3.11. In-vitro drug release study Experiments on the in vitro drug release of ocular films have been conducted using a dialysis membrane placed between the glass test tube's donor and receptor compartments. After a 12-hour period, the produced batches' cumulative drug release percentage had been found to fall between 71.35 ± 0.02% and 91.25661 ± 0.005%. The outcome demonstrates that the release of medication rises with the quantity of polymer. Table 5 presents the results, which demonstrate that the drug release findings for each formulation (P1 to P9). Batch P2 exhibits a more consistent and targeted medication release compared to previous batches. 3.12. Kinetic release study The medication release kinetic profile (optimal formulation) has been identified by applying mathematical analysis to data derived from an in-vitro drug release investigation. As shown in Table 8 , the Higuchi model was selected as the model with the greatest R2 value and N value over 0.5 for film formulation, confirming non-fickain drug delivery mechanism. The P2 formulation’s drug release behavior was best described by this model. The zero-order, first -order, Korsmeyer-peppas, and Higuchi models are depicted in Figs. 8, 9, 10, and 11 respectively. Table 8 The correlation coefficients obtained by fitting the release data in different kinetical models. Formulation Zero order First order Higuchi model Korsmeyer-Peppas model Best fit model Correlation Coefficient (R 2 ) n P2 0.9423 0.6262 0.99 0.9364 0.64 Higuchi model 3.13. Stability study The physical and chemical properties of ocular film (P2) did not significantly change during the entire period of stability testing, indicating that the generated films proved secure even under stressful storage conditions for six months (Table 9 ). Table 9 Stability study of prednisolone ocular film. Temperature 40 Ċ/ 75% RH Formulation Moisture absorption% Moisture loss% Drug content Before After Before After Before After P2 5.79 ± 1.05 5.4 ± 1.8 8.96 ± 0.46 8.1 ± 0.3 99.93 ± 0.005 99.93 ± 0.004 3.14. In-vivo study (Eye irritancy study) In this test, the formulation P2 was employed. It was discovered to be non-irritating and to have no adverse effects on the cornea, iris, or conjunctiva as displayed in the Table 10 . So, the formulation was appropriate for installing eyes. After 24 hours, the formulation P2's ocular safety score was found to be under control; as a result, it was deemed to be just moderately irritating. The chemical solvent that was utilized to prepare the rate-regulating membrane may be to blame for this discomfort. Therefore, it may be said that administering them to the eyes was safe. Table 10 Ocular irritancy test as per Draize test procedure. Eye part Cornea Iris Conjunctiva Total Score 0 0 0 0 4. DISCUSSION The study was conducted to enhance the bioavailability and retention time of ocular medication in the eye. It aimed to formulate ocular films of Prednisolone for the treatment of dry eye using the solvent casting method. Glycerin was used as a plasticizer, imparting soothing and elastic properties to the films. The increase in bioavailability was demonstrated through in vitro release studies, while prolonged ocular retention was confirmed via ocular irritancy tests conducted on rabbits. Solvent casting method is an easy and convenient method for preparing ocular films. The results of the ocular irritancy test indicated that the films did not cause any ocular toxicity or irritation. CONCLUSION Solvent casting was used to create and optimize prednisolone ocular films. The study's data indicate that the prednisolone optimized ocular films made with the Central Composite Design method were adequate and legitimate It was discovered that P2, which was smooth, transparent, and flexible. In contrast to other formulations, the physicochemical characteristics such as weight and thickness uniformity, folding durability, surface pH, swelling index, % moisture absorption, and percentage moisture loss demonstrated optimal results and superior drug content uniformity. After 12 hours, the P2 formulation showed 90.75% drug release. Hence, compared to other formulations, the P2 formulation had the largest sustained drug release. The drug release pattern at 12 hours seemed to be controlled by Higuchi kinetics, and the transport mechanism had been demonstrated to be non-fickian. The stability of this improved formulation got tested. The ocular insert performed the sterility test, and the physicochemical characteristics did not significantly alter between the 0th and 60th day. Thus, it was discovered that the formulation proved robust. When applied to rabbit eye, the optimized film exhibited no toxicity or ocular irritation, and it was deemed safe. The aforementioned findings suggest that prednisolone ocular films can be applied to the corneal surface of the eye in a regulated manner and for a prolonged amount of time. It is possible to modify the medication release pattern from these films by adjusting various formulation parameters. With advantages like longer residence times, longer drug releases, and less administration frequency, the aforementioned promising formulation (P) would undoubtedly boost patient compliance. Pharmacokinetic studies in rabbits might be used to determine the therapeutic usefulness of this approach in future research. Abbreviations CCD Central Composite Design P Prednisolone MMP-9 Matrix metalloproteinase-9 STF Saline tear fluid PVP Polyvinyl Pyrrolidone Declarations CONFLICT OF INTEREST The authors of this research declare that they have no conflicts of interest. FUNDING None Author Contribution V.P. performed all parameters in the laboratories and wrote the initial draft. S.V. Contributed to the structure and critical review. P. V. reviewed the final manuscript. All authors have read and approved the final manuscript. Acknowledgement The authors express their gratitude to the Noida Institute of Engineering and Technology for providing the resources they needed to carry out their investigation. References Flanagan JL, Willcox MDP. Role of lactoferrin in the tear film. Biochimie. 2009;91(1):35–43. Taghe S, Mirzaeei S, Ahmadi A. Preparation and evaluation of nanofibrous and film-structured ciprofloxacin hydrochloride inserts for sustained ocular delivery: pharmacokinetic study in rabbit’s eye. Life. 2023;13(4):913. Achouri D, Alhanout K, Piccerelle P, Andrieu V. Recent advances in ocular drug delivery. Drug Dev Ind Pharm. 2013;39(11):1599–617. Lemp MA, Sullivan BD, Crews L. A. Biomarkers in dry eye disease. Eur Ophthalmic Rev. 2012;6(3):157–63. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol, 2009;405–12. Latkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol. 2008;19(4):287–91. Coursey TG, Henriksson JT, Marcano DC, Shin CS, Isenhart LC, Ahmed F, Acharya G. Dexamethasone nanowafer as an effective therapy for dry eye disease. J Controlled Release. 2015;213:168–74. Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol. 2008;146(3):350–6. Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease. Int Rev Immunol. 2013;32(1):19–41. Coursey TG, de Paiva CS. Managing Sjögren’s Syndrome and non-Sjögren Syndrome dry eye with anti-inflammatory therapy. Clin Ophthalmol, 2014;1447–58. Peck T, Olsakovsky L, Aggarwal S. Dry eye syndrome in menopause and perimenopausal age group. J mid-life health. 2017;8(2):51–4. Versura P, Giannaccare G, Campos EC. Sex-steroid imbalance in females and dry eye. Curr Eye Res. 2015;40(2):162–75. Zhang X, Zhao L, Deng S, Sun X, Wang N. Dry eye syndrome in patients with diabetes mellitus: prevalence, etiology, and clinical characteristics. J Ophthalmol, 2016(;1), 8201053. Abd-Allah NM, Hassan AA, Omar G, Hamdy M, Abdelaziz STA, El Hamid A, W. M., Moussa RA. Dry eye in rheumatoid arthritis: relation to disease activity. Immunological Med. 2020;43(2):92–7. Yumori JW, Trinh D, Lee E, Escobedo T, Hollands G, Gordon R, Finley M. Prevalence of dry eye disease in rheumatoid arthritis patients. Investig Ophthalmol Vis Sci. 2015;56(7):4437–4437. Mendoza-Santiesteban CE, Hedges TR III, Norcliffe-Kaufmann L, Warren F, Reddy S, Axelrod FB, Kaufmann H. Clinical neuro-ophthalmic findings in familial dysautonomia. J Neuroophthalmol. 2012;32(1):23–6. 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Contact lens strategies for the patient with dry eye. Ocul Surf. 2007;5(4):294–307. CHAUDHARI PD, DESAI US. Formulation and evaluation of niosomal in situ gel of prednisolone sodium phosphate for ocular drug delivery. Int J Appl Pharm, 2019;97–116. Hassan H, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 2021;26(18):5432. Albash R, El-Dahmy RM, Hamed MI, Darwish KM, Alahdal AM, Kassem AB, Fahmy AM. Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, in-silico and in-vivo studies. Drug Delivery. 2022;29(1):2784–95. Patil SS, Bade A, Tagalpallewar A. Design, optimization and pharmacodynamic comparison of dorzolamide hydrochloride soluble ocular drug insert prepared by using 32 factorial design. 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Iran J Pharm research: IJPR. 2015;14(Suppl):23. Bansal H, Khatry S, Arora S. Formulation and evaluation of programmed release ocular inserts of mizolastine. Int J Pharm Sci Res. 2013;4(1):497. Mathurm M, Gilhotra RM. Glycerogelatin-based ocular inserts of aceclofenac: physicochemical, drug release studies and efficacy against prostaglandin E2-induced ocular inflammation. Drug Delivery. 2011;18(1):54–64. Mahajan HS, Deshmukh SR. Development and evaluation of gel-forming ocular films based on xyloglucan. Carbohydr Polym. 2015;122:243–7. Mehrandish S, Mohammadi G, Mirzaeei S. Preparation and functional evaluation of electrospun polymeric nanofibers as a new system for sustained topical ocular delivery of itraconazole. Pharm Dev Technol. 2022;27(1):25–39. Tofighia P, Soltani S, Montazam SH, Montazam SA, Jelvehgari M. Formulation of tolmetin ocuserts as carriers for ocular drug delivery system. Iran J Pharm research: IJPR. 2017;16(2):432. Dave V, Paliwal S, Yadav S. Formulation and evaluation of controlled delivery of aceclofenac through ocular insert. Turkish J Pharm Sci. 2013;10(2):205–20. Viswanath V, Narasimharao B, Purushothaman M, Sowjanya G, Sreevani S. Formulation and evaluation of fluconazole ocular inserts. World J Pharm Res. 2015;4:828–41. Bhandari L, Patil AS, Bolmal U, Masareddy R, Dandagi P. Formulation and evaluation of natamycin solid dispersion incorporated ophthalmic films. Indian J Pharm Educ Res, 2022; 56 . Jethava JK, Jethava GK. Design, formulation, and evaluation of novel sustain release bioadhesive in-situ gelling ocular inserts of ketorolac tromethamine. Int J Pharm Invest. 2014;4(4):226. Bohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Convergence. 2016;3(1):3. Ahad HA, Ishaq BM, Shaik M, Bandagisa F. Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone. Pak J Pharm Sci, 2016; 29 (3). Pawar PK, Katara R, Majumdar DK. Design and evaluation of moxifloxacin hydrochloride ocular insert. Acta Pharm. 2012;62(1):93–104. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7283794","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":496373439,"identity":"ce4e9a84-15fc-4257-810e-0a651c2ff842","order_by":0,"name":"Vindhya Pal","email":"","orcid":"","institution":"Medicef Pharma, Plot No 4, Pocket-8, Sector 19, Rohini New Delhi, Delhi-110089","correspondingAuthor":false,"prefix":"","firstName":"Vindhya","middleName":"","lastName":"Pal","suffix":""},{"id":496373440,"identity":"c604a87a-fbd0-4ea7-bee6-6b9e44c1ff9c","order_by":1,"name":"Sushma 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06:18:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":359458,"visible":true,"origin":"","legend":"\u003cp\u003eThickness \u003cstrong\u003e(a)\u003c/strong\u003e contour surface plot \u003cstrong\u003e(b)\u003c/strong\u003e 3D response surface plot.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/d6a79a6e39d7df084ad8cf07.png"},{"id":88751292,"identity":"801ff361-3047-4d2f-8d4c-47ba78be4b5e","added_by":"auto","created_at":"2025-08-11 06:18:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":404420,"visible":true,"origin":"","legend":"\u003cp\u003eDrug Release (%) \u003cstrong\u003e(a)\u003c/strong\u003e contour surface plot \u003cstrong\u003e(b)\u003c/strong\u003e 3D response surface plot.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/31340175a4522d98af4348a2.png"},{"id":88751295,"identity":"6c3d3d61-5c87-4d8c-9577-183170a583c9","added_by":"auto","created_at":"2025-08-11 06:18:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":409371,"visible":true,"origin":"","legend":"\u003cp\u003epH \u003cstrong\u003e(a)\u003c/strong\u003e contour surface plot \u003cstrong\u003e(b)\u003c/strong\u003e 3D response surface plot.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/7c7873587c50f19265962b4b.png"},{"id":88751933,"identity":"751b551c-123f-4bb6-8fa9-ab27005f7981","added_by":"auto","created_at":"2025-08-11 06:26:04","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":24050,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThickness of the Prednisolone ocular film Formulations (P1-P9)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/5a57fa3138dcf7bedd698a34.png"},{"id":88751934,"identity":"7e3f62ca-6c36-4863-a198-0f4b588be853","added_by":"auto","created_at":"2025-08-11 06:26:04","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":24252,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003epH of the Prednisolone ocular films (P1-P9)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/d339775f50ffce975126de1c.png"},{"id":88751293,"identity":"ac591ea5-e0fc-43d9-9a10-49a2faff03ac","added_by":"auto","created_at":"2025-08-11 06:18:04","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":26041,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSwelling Index of the prepared formulations (P1-P9)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/0f7f6cc83383d5f10f147e89.png"},{"id":88752977,"identity":"796b7920-d2c9-45b9-b36c-ee46b67ae0fa","added_by":"auto","created_at":"2025-08-11 06:42:04","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":32668,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eZero order release kinetic model for P2 formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/3a57d2db98777da18cc0a4ec.png"},{"id":88751935,"identity":"35c25684-4d21-45f2-88a2-b06217d49b1e","added_by":"auto","created_at":"2025-08-11 06:26:04","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":29863,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFirst order release kinetic model for P2 formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/da3c3da9ed665a11d1ee253a.png"},{"id":88751938,"identity":"21d36770-35ff-439b-971b-93cb9bd10246","added_by":"auto","created_at":"2025-08-11 06:26:04","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":30979,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHiguchi release kinetic model for P2 formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/36e005da951b97ae7fde5917.png"},{"id":88751298,"identity":"18e26b68-bcf8-4835-a3c0-78293294ea8e","added_by":"auto","created_at":"2025-08-11 06:18:04","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":59511,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKorsmeyer-Peppas release kinetic model for P2 formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/7797636e7d513a876d7a1c95.png"},{"id":93321163,"identity":"4c5933a0-ec2c-4b67-bc59-0409c1aaee0c","added_by":"auto","created_at":"2025-10-12 06:01:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3078491,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7283794/v1/258e67b4-2252-466b-a2bc-fbd1c0dc9c6c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Development and Optimization of Eudragit® L100 Film for Ocular Delivery of Prednisolone for Dry Eye","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eThe eye is a sensory organ, establish the sense of sight through tear film turnover and blinking and it protect from external harmful stimuli [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It involves complex defense mechanism along with continuous elimination of lachrymal fluid. The persistent drain of lacrimal fluid halt ocular retention and intraocular penetration of the drug in several ocular ailments such dry eyes, conjunctivitis, etc. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. One of the most prevalent ocular conditions, dry eye affects between 30 to 40\u0026nbsp;million individuals in the US alone and is a serious public health problem [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It is associated with corneal surface epithelial illness, lighting sensibility, impaired vision, and eye discomfort [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Furthermore, it serves as one of the main reasons for clinical examinations, and about 30% of patients claim to have mild or chronic dry eye symptoms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAutoimmunity [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], hormonal imbalance [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], systemic disorders [\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], genetic diseases [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], nerve injury [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and gut dysbiosis [\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] are examples of situations that are considered intrinsic factors. Dry eye can be made worse by a continuous increase in visually demanding computer screen work and contact lens use [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Numerous of these causal variables have a negative effect on either or both of the meibomian glands, the eye surface, the lacrimal glands, and the accompanying network of neurons, which are components of the lacrimal functioning unit [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Artificial tear drops, which hydrate and lubricate the eye, have no pharmacologic action, and only offer transient relief, are the main treatment for mild dry eye [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Inflammation linked to chronic dry eye frequently reacts topically to corticosteroids and cyclosporine-A eye drops [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAn artificial glucocorticoid made from cortisol is called prednisolone. As a model drugs in the current study, prednisolone acetate or sodium phosphate are used as ophthalmic suspensions in eye drops to lessen allergic responses that affect the eye and to ease the associated symptoms including redness, swelling, and itching of the eye [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Prednisolone reduces inflammation by reversing the treatment's increased capillary permeability and inhibiting polymorphonuclear leukocyte movement [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the current study, Prednisolone ocular films were created by combining Polyvinyl pyrrolidone K-30 using glycerine in various proportions to lengthen the pre-corneal occupancy period and reduce the duration of medication application. This research project aims to produce an ocular film using the solvent casting process. Using a two-factor and five-level Central Composite Design, the formulation was adjusted with respect to Polyvinyl pyrrolidone K-30, glycerin, thickness, pH, and drug release in 12 hours. For in-vivo ocular irritation in albino rabbits, the most effective formulation was investigated.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e2.1. Materials\u003c/h2\u003e\n\u003cp\u003ePrednisolone was collected from Central Drug House (P) Ltd., Delhi, India. The following excipients were purchased from Central Drug House (P) Ltd., Delhi, India: Eudragit\u0026reg; L 100, Polyvinyl Pyrrolidone K-30(PVP K-30) and Glycerine. Analytical grade substances and solvents were utilized in the formulation.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2. Methods\u003c/h2\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.1. Experimental design\u003c/h2\u003e\n\u003cp\u003eThe impact of independent variables, polyvinyl pyrrolidone K-30 and glycerine, on three response variables\u0026mdash;thickness, drug release, and pH were examined using a two-factor Central Composite Design. Using Design Expert\u0026reg; software version 13 (Stat-Ease Software), an overall number of nine experiments originated from CCD. One replication of each of the four axial, four factorial, and one center point were included in the randomized sequence of the experiment. Regression analysis on the response surface was used to examine the data. The model selection depended on the Design Expert software's significant terms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), least significant lack of fit, coefficient of variance, and multiple correlation coefficients [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]. Following that, the desirability function was used to guide the chosen formula selection, enabling simultaneous analysis of every answer. It was chosen to go with a proposal having the lowest thickness and pH and the maximum percentage of medication release. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e shows that the option exhibiting the greatest desirability (nearly one) had been chosen. The chosen formula had been further explained [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. The coded and actual values of the independent variables from the optimization procedure are displayed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCoded and Actual value of the optimized formulations.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFormulations\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCoded Value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eActual Value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePolyvinyl Pyrrolidone K-30 (mg)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGlycerine (mL)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePolyvinyl Pyrrolidone K-30 (mg)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGlycerine (mL)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026alpha;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e641.42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026alpha;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.42\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u0026alpha;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.59\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u0026alpha;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e358.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u0026thinsp;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eVariables: - +\u0026alpha;\u0026thinsp;=\u0026thinsp;maximum; -\u0026alpha;\u0026thinsp;=\u0026thinsp;minimum; +1\u0026thinsp;=\u0026thinsp;high; -1\u0026thinsp;=\u0026thinsp;low; 0\u0026thinsp;=\u0026thinsp;Mean\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.2. Method of preparation of Ocular films\u003c/h2\u003e\n\u003cp\u003eThe ocular film was prepared using the solvent casting method. To generate a homogenous dispersion, predetermined polymers were combined with 30 ml of solvent and swirled for two hours. subsequently measured quantities of Prednisolone were included and agitated for another two hours using a magnetic stirrer. A sufficient quantity of glycerine was put in and thoroughly blended. The final product was cast onto the petri dish. The films undergo drying at room temperature for 48 hours, and then they are sliced utilising a cork borer, sealed with aluminium foil, and kept for more study. The mixture of the multiple batches is displayed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eFormulations of Ocular films loaded with Prednisolone\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eIngredients\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003eBatches\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP4\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP5\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP6\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP7\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP8\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP9\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrednisolone (mg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEudragit\u0026reg; L100 (mg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePolyvinyl Pyrrolidone K-30 (mg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e641.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e358.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlycerine (mL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.585\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDistilled water (mL)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eq.s.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\"\u003eq.s\u0026thinsp;=\u0026thinsp;sufficient quantity; mg\u0026thinsp;=\u0026thinsp;milligram; mL\u0026thinsp;=\u0026thinsp;milliliter\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.3. Thickness measurement\u003c/h2\u003e\n\u003cp\u003eVernier calliper was employed to examine the thickness of the ocular film and record the mean of the measurements [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.4. Folding endurance\u003c/h2\u003e\n\u003cp\u003eBy hand folding Prednisolone ocular film repeatedly at the same spot until it cracked or started to show indications of breaking was carried out for measuring folding endurance. The folding endurance score is based on the number of instances the film can be rolled in the same location without shattering [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.5. Surface pH\u003c/h2\u003e\n\u003cp\u003ePrednisolone ocular film allowed to swell for 30 minutes in a closed Petri dish with 1 ml of distilled water. The expended film had been removed, and the solution's pH level had been measured utilizing a digital pH metre [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.6. Drug content\u003c/h2\u003e\n\u003cp\u003eThree films were obtained from each batch of the formulation to verify that the medication was uniformly distributed across the ocular film. Each film was placed within a glass vail that held 10 ml of STF. With the help of a magnetic stirrer, the film disappeared and the resulting solution got filtered. 1 ml of the filtrate got separated and mixed with 10 ml of purified water. The absorbance had been assessed utilizing UV spectroscopy at 242 nm [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.7. Weight uniformity\u003c/h2\u003e\n\u003cp\u003eTo ensure consistent weight, five films had been selected from each batch (n) and separately weighed on a digital scale. The ocular film's average weight was noted [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.8. Swelling index\u003c/h2\u003e\n\u003cp\u003eThe swelling test has been employed to investigate the effects of polymer hydration and bulk hydrophilicity on the release of medications through polymeric matrix. To quantify the swelling of polymeric films, the films were measured and then placed on a Petri dish with Saline tear fluid (STF) maintained at 32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 \u0026ordm;C and pH 7.4. The films were removed out at predetermined intervals of up to 60 minutes, weighed, and finally put reverse into the same container. Utilizing the following equation, the amount of solvent absorption was estimated as the swelling index [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003e\u003cstrong\u003eSwelling index ═ [Wt \u0026ndash; W0/ W0] X 100------- (1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhere, W0 is the initial weight of the sample and Wt its weight at time at time t.\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.9. % Moisture Absorption\u003c/h2\u003e\n\u003cp\u003eThe % moisture absorption analysis has been evaluated the film's stability or structural strength in humid conditions. The films were weighed before being put in a desiccator with 100 ml of overexposed sodium chloride solution. After three days, the films were removed and weighed once more [\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e43\u003c/span\u003e]. The following formula used to determine the percentage of moisture absorption:\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003e\u003cstrong\u003e% Moisture Absorption\u0026thinsp;=\u0026thinsp;Final weight \u0026ndash; Initial weight/ Initial weight X 100\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.10. % Moisture Loss\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eThis test was done to make sure the ocular films were intact when they were dry. The ocular implants were precisely weighed and stored in a dehydrated calcium chloride-filled desiccator. After three days, the films were removed, weighed, and the % moisture loss was determined utilizing a formula: [\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003e\u003cstrong\u003e% Moisture Loss\u0026thinsp;=\u0026thinsp;Initial weight \u0026ndash; Final weight/ Initial weight X 100\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2.11. \u003cem\u003eIn-vitro\u003c/em\u003e drug release study\u003c/h2\u003e\n\u003cp\u003eThe traditional standard cylindrical tube made in the lab was used to perform the \u003cem\u003ein-vitro\u003c/em\u003e permeation of medication taken from different ocular film. A simple modification of open ended glass tube was used. The open tube's end, which served as the donor compartment, had the diffusion cell membrane attached to it. This compartment contained an ocular film. The membrane of the diffusion cell served as the corneal epithelium. The receptor compartment, which contained 80 ml of STF in a 100 ml beaker, was in directly contact with the whole surface of the membrane. The contents of the receptor compartment seemed continuously mixed with a magnetic stirrer during the temperature continued to stay at 37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 \u0026ordm;C. At predefined intervals, 5 ml of the receptor compartment medium was taken out for completely fresh STF. Following the necessary dilutions against the reference and the use of STF as a blank, the aliquots were examined for the presence of the medication utilizing a UV-Visible Spectrophotometer (Pharmaspec 1700, Shimadzu, Japan) at 242 nm [\u003cspan class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv id=\"Sec15\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.12. Kinetic Release Study\u003c/h2\u003e\n\u003cp\u003eSeveral kinetic models were employed to characterize the release kinetics in order to interpret the in vitro drug release data [\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZero-order\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe zero order rate Eq.\u0026nbsp;(1) explains the systems where the rate of drug release rises with time.\u003c/p\u003e\n\u003cp\u003eC\u0026thinsp;=\u0026thinsp;k\u003csub\u003e0\u003c/sub\u003et (1)\u003c/p\u003e\n\u003cp\u003ewhere, C is the concentration of drug at time t, t is the time and k0 is zero-order rate constant expressed in units of concentration/time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFirst-order\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe first order Eq.\u0026nbsp;(2) explains the release from the system where rate of drug release is concentration dependent.\u003c/p\u003e\n\u003cp\u003eLog C\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;\u0026minus;\u0026thinsp;Log C\u0026thinsp;=\u0026thinsp;k\u003csub\u003e1\u003c/sub\u003et/2.303 (2)\u003c/p\u003e\n\u003cp\u003ewhere, C\u003csub\u003e0\u003c/sub\u003e is the initial concentration of drug and k\u003csub\u003e1\u003c/sub\u003e is the first order rate constant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHiguchi diffusion model\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHiguchi described the release of drugs from the ocular film as a square root of time dependent process based on Fickian diffusion Eq.\u0026nbsp;(3).\u003c/p\u003e\n\u003cp\u003eC\u0026thinsp;=\u0026thinsp;K\u003csub\u003eH\u003c/sub\u003e \u0026radic; t (3)\u003c/p\u003e\n\u003cp\u003ewhere, K\u003csub\u003eH\u003c/sub\u003e is the constant reflecting the design variables of the system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKorsmeyer-Peppas\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKorsmeyer et al. derived a simple mathematical relationship which described the drug release from a polymeric system Eq.\u0026nbsp;(4).\u003c/p\u003e\n\u003cp\u003eM\u003csub\u003et\u003c/sub\u003e / M\u003csub\u003e\u0026infin;\u003c/sub\u003e = K\u003csub\u003eKP\u003c/sub\u003et\u003csup\u003en\u003c/sup\u003e (4)\u003c/p\u003e\n\u003cp\u003ewhere M\u003csub\u003et\u003c/sub\u003e /M\u003csub\u003e\u0026infin;\u003c/sub\u003e is the fraction of drug released at time t, K\u003csub\u003eKP\u003c/sub\u003e is the rate constant and n are the release exponent.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.13. Stability study\u003c/h2\u003e\n\u003cp\u003eAccelerated stability observations can be used to estimate how the films' self-life is generated. In the current experiment, films from particular batches were chosen and tightly packed in amber-colored decanters that had been stopped and ploughed with cotton. For six months, they were put under 40\u0026deg;C/75% RH stress storage conditions. At specified intervals, the films were put in 5ml of STF and rotate in a rotary shaking mixer (50rpm). Using a 0.45 \u0026micro; filter, the solution was cleared after 24 hours. After properly diluting the filtrate with STF, the absorbance was restricted to 242 nm [\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.14. \u003cem\u003eIn-vivo\u003c/em\u003e study (Eye irritancy study)\u003c/h2\u003e\n\u003cp\u003eAIIMS (All India Institute of Medical Sciences), New Delhi-110029's Central Animal Facility, Ansari Nagar, granted permission for the study's use of animals. The approval number for animal ethics is IAEC/NIET/2022/02/46. The \u003cem\u003ein vivo\u003c/em\u003e ocular irritation test was performed on either sexed, 2.8 to 4.1 kg New Zealand rabbits. Free leg and eye movement had been allowed. The Draize test has been employed to evaluate eye discomfort. The measurements made using a scoring method proved that the generated ocular films in rabbit eyes were safe. Three animals made up the control group and six animals made up the groups participating in the experiment. Animals in the control group got saline solution in both eyes. All of the animals in the experimentation groups had the films placed in both eyes. For five days, this was done once every 24 hours [\u003cspan class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eOcular safety test using the Draize irritancy scale.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEye\u0026nbsp;tissue\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGrading system\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCalculations\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCornea:\u0026nbsp;Opacity\u0026nbsp;(O)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,1,2,3,4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eO\u0026times;A\u0026times;5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e80\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eArea\u0026nbsp;involved\u0026nbsp;(A)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,1,2,3,4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIris:\u0026nbsp;Values\u0026nbsp;for\u0026nbsp;congestion and\u0026nbsp;hemorrhage\u0026nbsp;(I)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,\u0026nbsp;1,\u0026nbsp;2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eI\u0026times;5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConjunctiva:\u0026nbsp;Redness\u0026nbsp;(R)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,\u0026nbsp;1,\u0026nbsp;2,3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChemosis\u0026nbsp;(C)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,1,2,3,4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(R\u0026thinsp;+\u0026thinsp;C\u0026thinsp;+\u0026thinsp;D) \u0026times;2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDischarge\u0026nbsp;(D)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,\u0026nbsp;1,\u0026nbsp;2,3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal\u0026nbsp;Maximum\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e110\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e Scores of 0 and 4 indicate severe conditions for O, R, C, and D, respectively. A corneal coverage scores of 1, 2, 3, or 4 indicates how much of the cornea is protected. Scores between 0 and 2 indicate severity in the case of I.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eChart for safety evaluation.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eScores\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAssessing\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.0\u0026ndash;0.5\u003c/p\u003e\n\u003cp\u003e0.5\u0026ndash;2.5\u003c/p\u003e\n\u003cp\u003e2.5\u0026ndash;15.0\u003c/p\u003e\n\u003cp\u003e15.0\u0026ndash;25.0\u003c/p\u003e\n\u003cp\u003e25.0\u0026ndash;50.0\u003c/p\u003e\n\u003cp\u003e50.0\u0026ndash;80.0\u003c/p\u003e\n\u003cp\u003e80.0\u0026ndash;110.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot irritable\u003c/p\u003e\n\u003cp\u003eVirtually\u0026nbsp;not\u0026nbsp;irritable\u003c/p\u003e\n\u003cp\u003eMinimally\u0026nbsp;irritable\u003c/p\u003e\n\u003cp\u003eMildly\u0026nbsp;irritable\u003c/p\u003e\n\u003cp\u003eModerately\u0026nbsp;irritable\u003c/p\u003e\n\u003cp\u003eSeverely\u0026nbsp;irritable\u003c/p\u003e\n\u003cp\u003eExtremely\u0026nbsp;irritable\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\n\u003ch2\u003e3.1. Formulation of Prednisolone loaded ocular films\u003c/h2\u003e\n\u003cp\u003eThe transparent and flexible films would be produced by concentration of Eudragit\u0026reg; L 100, Polyvinyl Pyrrolidone K-30(PVP K-30) and Glycerine. Eudragit\u0026reg; L 100 and Polyvinyl Pyrrolidone K-30 were included as polymer, while Glycerine served as a consistent plasticizer agent. The glycerine concentration of notably affected the flexibility of the ocular films. Figure\u0026nbsp;1 shown the formulation of Prednisolone loaded ocular films.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n\u003ch2\u003e3.2. Data analysis, statistical optimization and validation\u003c/h2\u003e\n\u003cp\u003eThe impact of formulation factors on thickness, percent drug release, and pH was investigated in a total of nine studies. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e contains the response data for every experiment.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eExperimental runs, independent variables, and measured responses of prednisolone ocular films.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRun\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFactor A\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFactor B\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResponse (R\u003csub\u003e1\u003c/sub\u003e)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResponse (R\u003csub\u003e2\u003c/sub\u003e)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResponse (R\u003csub\u003e3)\u003c/sub\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.243\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e76.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.026\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.506\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e90.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e641.421\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.568\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e91.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.41421\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.456\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e80.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.413\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e86.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e400\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.271\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e78.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.585786\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.428\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e82.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e358.579\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.178\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e71.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.017\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.567\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e88.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.153\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote: Factor A\u003c/strong\u003e: Polyvinyl pyrrolidone K-30 (mg); \u003cstrong\u003eFactor B\u003c/strong\u003e: Glycerine (ml); \u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/sub\u003e: Thickness (mm); \u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e: % Drug release; \u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sub\u003e: pH.\u003c/p\u003e\n\u003cp\u003eThe value of responses R\u003csub\u003e1\u003c/sub\u003e (Thickness), R\u003csub\u003e2\u003c/sub\u003e (% Drug release) and R\u003csub\u003e3\u003c/sub\u003e (pH) ranges from 0.178 to 0.568 mm, 71.35 to 91.25% and 6.8 to 7.6 respectively.\u003c/p\u003e\n\u003cp\u003eThe best-fitting model recommended by the software was linear for R2 and R3, and quadratic for R1. The recommended models proved to be relevant for functional variables by the results of ANOVA and regression analysis, since each model has a probability value less than 0.05 (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab6\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSummary of results of regression analysis and ANOVA for measured responses.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eResponses\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eModel\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAdjusted R\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePredicted R\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSS\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDF\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMS\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eF value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eModel significance\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eQuadratic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9984\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9959\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e(NA)\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.1620\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0324\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e385.68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignificant\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eR\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLinear\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9071\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.8699\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e349.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e174.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0003\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignificant\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eR\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLinear\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.8747\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.8330\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6938\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.7309\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.3654\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20.95\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.0020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignificant\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/sub\u003e: Thickness; \u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e: % Drug release; \u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sub\u003e: %pH; \u003cstrong\u003eSS\u003c/strong\u003e: Sum of Square; \u003cstrong\u003eDF\u003c/strong\u003e: Degree of freedom; \u003cstrong\u003eMS\u003c/strong\u003e: mean square\u003c/p\u003e\n\u003cp\u003eThe relevant polynomial equations for the dependent variable were recommended by software;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.4130\u0026thinsp;+\u0026thinsp;0.1390A\u0026thinsp;+\u0026thinsp;0.0091B\u0026thinsp;+\u0026thinsp;0.0222AB \u0026ndash; 0.0225A\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;+\u0026thinsp;0.0117B\u003csup\u003e2\u003c/sup\u003e (5)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;+\u0026thinsp;83.01\u0026thinsp;+\u0026thinsp;6.56A \u0026ndash; 0.8420B (6)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;+\u0026thinsp;7.18\u0026ndash;0.2966A \u0026ndash; 0.0582B (7)\u003c/p\u003e\n\u003cp\u003eFrom Eq.\u0026nbsp;5, it is clear that variables A and B have a positive influence, meaning that thickness grows in tandem with rises in PVP K-30 proportion and glycerine level. The entire impact of A and B on thickness is positive, although the exponentially increasing form of A and B also has a positive influence on thickness. Drug release percentage was positively and negatively impacted by factors A and B (Eq.\u0026nbsp;6). Thus, drug release rises with polymer concentration whereas drug release percentage decreases with increasing glycerine concentration. A and B had a negative effect on pH. Thickness, Drug release, and pH are depicted in surface contour plots and 3D response surface plots, respectively, in Figs.\u0026nbsp;2(a) \u0026amp; (b), \u003cstrong\u003e3\u003c/strong\u003e(a) \u0026amp; (b), and \u003cstrong\u003e4\u003c/strong\u003e(a) \u0026amp; (b), which were generated from the experimental design.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe optimal ocular film was chosen by applying a desirability search strategy. The optimized batch selected based on a formulation with reduced thickness, a medication release percentage of above 85%, a suitable pH, and less negatively potential. Furthermore, the potential influence on medication release was taken consideration while choosing the optimal batch. Numerous investigations have already demonstrated that medication release rises with the quantity of polymers. The batch that considered optimal was batch P2, which included 600 mg of PVP K-30 and 1 ml of glycerine with a desirability close to 1.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n\u003ch2\u003e3.3. Thickness measurements\u003c/h2\u003e\n\u003cp\u003eThe films ranged in thickness from 0.178\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001 to 0.568\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005 mm. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;5 presents the findings. It shows that the manufactured prednisolone ocular films had a consistent thickness, that is discovered to be closely correlated with the polymer content.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n\u003ch2\u003e3.4. Folding Endurance\u003c/h2\u003e\n\u003cp\u003eBreaking strength and endurance were used to test the folding endurance of the prednisolone ocular film. This is the maximum number of times the film might be folded in one spot before breaking or showing signs of breaking. The folding endurance of the several formulations of prednisolone ocular films (P1 to P9) was determined to range between 185\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73 and 209\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64. This outcome demonstrates that the ocular implant has sufficient strength to resist handling shock. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e provides the corresponding outcomes.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\n\u003ch2\u003e3.5. Surface pH\u003c/h2\u003e\n\u003cp\u003eOcular films are compatible with lachrymal fluids, as indicated by the pH values on the surface of all the films, which ranged from 6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 to 7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;6 shows each of these values.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\n\u003ch2\u003e3.6. Drug content\u003c/h2\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e shows that the produced ocular films had a drug content value ranging from 99.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002 to 99.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.019%. This suggests that the medication was evenly dispersed throughout the polymeric matrix along with the preparation technique used produced the desired outcomes.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e\n\u003ch2\u003e3.7. Weight uniformity\u003c/h2\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e shows that the weights of the ocular films ranged from 51.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23 to 69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.18 mg. A proper dispersion of the medicine in the polymer and plasticizer is shown by the homogeneity of the weights of the films.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e\n\u003ch2\u003e3.8. Swelling index\u003c/h2\u003e\n\u003cp\u003eIn order to assess the hydrophilicity, hydration, and erosion of the films, the swelling capacity were examined. The pace at which fluid permeates the polymer matrix, the matrix's resistance to water molecules moving through it, and the matrix's final degradation all affect how much swelling results. The results show that all of the formulations generate reduced pain, with swelling index values ranging from 39.4%\u0026plusmn;0.65 to 72.21%\u0026plusmn;3.21 in 60 minutes. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e \u0026amp; Fig.\u0026nbsp;7 represents the results of each formulation.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\n\u003ch2\u003e3.9. % Moisture absorption\u003c/h2\u003e\n\u003cp\u003eFor each of the nine formulations, the percentage moisture absorption has been determined in triple. The results showed that because PVP polymers are hydrophilic, they had a greater absorption of moisture in the film comprising them. The percentage of moisture absorbed ranged from 3.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 to 5.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05, indicating that there was no deterioration in durability under highly humid circumstances. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e shows all of the results.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\n\u003ch2\u003e3.10. % Moisture loss\u003c/h2\u003e\n\u003cp\u003eThere was no difference in the films' dependability as the moisture content decreased. The percentage of moisture loss increased from 6.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 to 9.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6, indicating that the reliability remained unchanged in dry circumstances. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e presents the findings.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab7\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePhysical evaluations of prednisolone ocular films.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFormulations\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eThickness (mm)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFolding endurance\u003c/p\u003e\n\u003cp\u003e(No. of folds)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSurface pH\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eDrug content (%)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWeight uniformity (mg)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSwelling index (%)\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%Moisture absorption\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%Moisture loss\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.243\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e198\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e51.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e72.21\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.506\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e191\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e54.12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e69.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.568\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e194\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.018\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e50.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.456\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e185\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e53.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e51.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.413\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e201\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e45.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.271\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e203\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e55.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e48.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.428\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e198\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;4.18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.178\u0026thinsp;\u0026plusmn;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e205\u0026thinsp;\u0026plusmn;\u0026thinsp;5.56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e9.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e0.567\u0026thinsp;\u0026plusmn;\u0026thinsp;0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e209\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e6.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.153\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e56.87\u0026thinsp;\u0026plusmn;\u0026thinsp;4.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e65.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3.16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003e(All values in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S; n\u0026thinsp;=\u0026thinsp;3)\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003ch2\u003e3.11. In-vitro drug release study\u003c/h2\u003e\n\u003cp\u003eExperiments on the in vitro drug release of ocular films have been conducted using a dialysis membrane placed between the glass test tube's donor and receptor compartments. After a 12-hour period, the produced batches' cumulative drug release percentage had been found to fall between 71.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02% and 91.25661\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005%. The outcome demonstrates that the release of medication rises with the quantity of polymer. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e presents the results, which demonstrate that the drug release findings for each formulation (P1 to P9). Batch P2 exhibits a more consistent and targeted medication release compared to previous batches.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\n\u003ch2\u003e3.12. Kinetic release study\u003c/h2\u003e\n\u003cp\u003eThe medication release kinetic profile (optimal formulation) has been identified by applying mathematical analysis to data derived from an in-vitro drug release investigation. As shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e, the Higuchi model was selected as the model with the greatest R2 value and N value over 0.5 for film formulation, confirming non-fickain drug delivery mechanism. The P2 formulation\u0026rsquo;s drug release behavior was best described by this model. The zero-order, first -order, Korsmeyer-peppas, and Higuchi models are depicted in Figs.\u0026nbsp;8, 9, 10, and 11 respectively.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab8\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eThe correlation coefficients obtained by fitting the release data in different kinetical models.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFormulation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eZero order\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFirst order\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHiguchi model\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eKorsmeyer-Peppas model\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBest fit model\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation Coefficient (R\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9423\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.6262\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.9364\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHiguchi model\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\n\u003ch2\u003e3.13. Stability study\u003c/h2\u003e\n\u003cp\u003eThe physical and chemical properties of ocular film (P2) did not significantly change during the entire period of stability testing, indicating that the generated films proved secure even under stressful storage conditions for six months (Table \u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab9\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eStability study of prednisolone ocular film.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"7\" align=\"left\"\u003e\n\u003cp\u003eTemperature 40 Ċ/ 75% RH\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eFormulation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMoisture absorption%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eMoisture loss%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDrug content\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBefore\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAfter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBefore\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAfter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBefore\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAfter\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e99.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\n\u003ch2\u003e3.14. \u003cem\u003eIn-vivo\u003c/em\u003e study (Eye irritancy study)\u003c/h2\u003e\n\u003cp\u003eIn this test, the formulation P2 was employed. It was discovered to be non-irritating and to have no adverse effects on the cornea, iris, or conjunctiva as displayed in the Table \u003cspan class=\"InternalRef\"\u003e10\u003c/span\u003e. So, the formulation was appropriate for installing eyes. After 24 hours, the formulation P2's ocular safety score was found to be under control; as a result, it was deemed to be just moderately irritating. The chemical solvent that was utilized to prepare the rate-regulating membrane may be to blame for this discomfort. Therefore, it may be said that administering them to the eyes was safe.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab10\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eOcular irritancy test as per Draize test procedure.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEye\u0026nbsp;part\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCornea\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIris\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eConjunctiva\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScore\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThe study was conducted to enhance the bioavailability and retention time of ocular medication in the eye. It aimed to formulate ocular films of Prednisolone for the treatment of dry eye using the solvent casting method. Glycerin was used as a plasticizer, imparting soothing and elastic properties to the films. The increase in bioavailability was demonstrated through in vitro release studies, while prolonged ocular retention was confirmed via ocular irritancy tests conducted on rabbits. Solvent casting method is an easy and convenient method for preparing ocular films. The results of the ocular irritancy test indicated that the films did not cause any ocular toxicity or irritation.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eSolvent casting was used to create and optimize prednisolone ocular films. The study's data indicate that the prednisolone optimized ocular films made with the Central Composite Design method were adequate and legitimate It was discovered that P2, which was smooth, transparent, and flexible. In contrast to other formulations, the physicochemical characteristics such as weight and thickness uniformity, folding durability, surface pH, swelling index, % moisture absorption, and percentage moisture loss demonstrated optimal results and superior drug content uniformity. After 12 hours, the P2 formulation showed 90.75% drug release. Hence, compared to other formulations, the P2 formulation had the largest sustained drug release. The drug release pattern at 12 hours seemed to be controlled by Higuchi kinetics, and the transport mechanism had been demonstrated to be non-fickian. The stability of this improved formulation got tested. The ocular insert performed the sterility test, and the physicochemical characteristics did not significantly alter between the 0th and 60th day. Thus, it was discovered that the formulation proved robust. When applied to rabbit eye, the optimized film exhibited no toxicity or ocular irritation, and it was deemed safe. The aforementioned findings suggest that prednisolone ocular films can be applied to the corneal surface of the eye in a regulated manner and for a prolonged amount of time. It is possible to modify the medication release pattern from these films by adjusting various formulation parameters. With advantages like longer residence times, longer drug releases, and less administration frequency, the aforementioned promising formulation (P) would undoubtedly boost patient compliance. Pharmacokinetic studies in rabbits might be used to determine the therapeutic usefulness of this approach in future research.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eCCD\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCentral Composite Design\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePrednisolone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eMMP-9\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMatrix metalloproteinase-9\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003eSTF\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eSaline tear fluid\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003e\u003cb\u003ePVP\u003c/b\u003e\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePolyvinyl Pyrrolidone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eCONFLICT OF INTEREST\u003c/h2\u003e\u003cp\u003eThe authors of this research declare that they have no conflicts of interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFUNDING\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eV.P. performed all parameters in the laboratories and wrote the initial draft. S.V. Contributed to the structure and critical review. P. V. reviewed the final manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors express their gratitude to the Noida Institute of Engineering and Technology for providing the resources they needed to carry out their investigation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFlanagan JL, Willcox MDP. Role of lactoferrin in the tear film. Biochimie. 2009;91(1):35\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTaghe S, Mirzaeei S, Ahmadi A. Preparation and evaluation of nanofibrous and film-structured ciprofloxacin hydrochloride inserts for sustained ocular delivery: pharmacokinetic study in rabbit\u0026rsquo;s eye. Life. 2023;13(4):913.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAchouri D, Alhanout K, Piccerelle P, Andrieu V. Recent advances in ocular drug delivery. Drug Dev Ind Pharm. 2013;39(11):1599\u0026ndash;617.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLemp MA, Sullivan BD, Crews L. A. Biomarkers in dry eye disease. Eur Ophthalmic Rev. 2012;6(3):157\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol, 2009;405\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLatkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol. 2008;19(4):287\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoursey TG, Henriksson JT, Marcano DC, Shin CS, Isenhart LC, Ahmed F, Acharya G. Dexamethasone nanowafer as an effective therapy for dry eye disease. J Controlled Release. 2015;213:168\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLemp MA. Advances in understanding and managing dry eye disease. 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Front Immunol. 2018;9:1106.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang R, Su C, Fang L, Lu J, Chen J, Ding Y. (2022). Dry eye syndrome: comprehensive etiologies and recent clinical trials. \u003cem\u003eInternational ophthalmology\u003c/em\u003e, 2022;\u003cem\u003e42\u003c/em\u003e(10), 3253\u0026ndash;3272.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUchino, M., Uchino, Y., Dogru, M., Kawashima, M., Yokoi, N., Komuro, A., \u0026hellip; Tsubota,K. Dry eye disease and work productivity loss in visual display users: the Osaka study.American journal of ophthalmology, 2014;157(2), 294\u0026ndash;300..\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLemp MA, Foulks GN. The definition and classification of dry eye disease. Ocul Surf. 2007;5(2):75\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmidl, D., Schmetterer, L., Witkowska, K. J., Unterhuber, A., Dos Santos, V. A.,Kaya, S., \u0026hellip; Garhofer, G. Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease. Cornea, 2015;34(4), 421\u0026ndash;426..\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKara N, Altinkaynak H, Goker Y, Yuksel K, Yildirim Y. Evaluation of corneal morphologic and functional parameters after use of topical cyclosporine-a 0.05% in dry eye. J Ocul Pharmacol Ther. 2012;28(6):593\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eElShaer A, Mustafa S, Kasar M, Thapa S, Ghatora B, Alany RG. Nanoparticle-laden contact lens for controlled ocular delivery of prednisolone: Formulation optimization using statistical experimental design. Pharmaceutics. 2016;8(2):14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSindt CW, Longmuir RA. Contact lens strategies for the patient with dry eye. Ocul Surf. 2007;5(4):294\u0026ndash;307.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCHAUDHARI PD, DESAI US. Formulation and evaluation of niosomal in situ gel of prednisolone sodium phosphate for ocular drug delivery. Int J Appl Pharm, 2019;97\u0026ndash;116.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHassan H, Adam SK, Alias E, Meor Mohd Affandi MMR, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 2021;26(18):5432.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlbash R, El-Dahmy RM, Hamed MI, Darwish KM, Alahdal AM, Kassem AB, Fahmy AM. Repurposing levocetirizine hydrochloride loaded into cationic ceramide/phospholipid composite (CCPCs) for management of alopecia: central composite design optimization, in-silico and in-vivo studies. Drug Delivery. 2022;29(1):2784\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatil SS, Bade A, Tagalpallewar A. Design, optimization and pharmacodynamic comparison of dorzolamide hydrochloride soluble ocular drug insert prepared by using 32 factorial design. \u003cem\u003eJournal of Drug Delivery Science and Technology\u003c/em\u003e, 2018;\u003cem\u003e46\u003c/em\u003e, 2018;138\u0026ndash;147.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhad HA, Chinthaginjala H, Bhupalam P, Dasari RR, Rao BS, Tarun K. Designing of dexamethasone sodium phosphate ocular films for madras eye: In vitro and in vivo evaluation. Pak J Pharm Sci, 2021;\u003cem\u003e34\u003c/em\u003e(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKumar A, Tiwari BK, Kumar S. OPTIMIZATION AND IN-VIVO EVALUATION OF OCULAR FILMS OF AN ANTI-INFLAMMATORY AGENT.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoateng JS, Popescu AM. 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Design, formulation, and evaluation of novel sustain release bioadhesive in-situ gelling ocular inserts of ketorolac tromethamine. Int J Pharm Invest. 2014;4(4):226.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBohrey S, Chourasiya V, Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Convergence. 2016;3(1):3.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhad HA, Ishaq BM, Shaik M, Bandagisa F. Designing and characterizing of tramadol hydrochloride transdermal patches prepared with Ficus carica fruit mucilage and povidone. Pak J Pharm Sci, 2016;\u003cem\u003e29\u003c/em\u003e(3).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePawar PK, Katara R, Majumdar DK. Design and evaluation of moxifloxacin hydrochloride ocular insert. Acta Pharm. 2012;62(1):93\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dry Eye, Prednisolone, Ocular Delivery, Optimization, Central Composite Design, Kinetic Study","lastPublishedDoi":"10.21203/rs.3.rs-7283794/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7283794/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eOne of the more prevalent ocular conditions, dry eye causes between 30 to 40 million individuals in the United States on its own and is a serious human medical issue. Ocular films of prednisolone were developed using a variety of polymeric methods to improve drug accumulation; these films showed benefits such as easier delivery and longer interaction times.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe major purpose of the current research focuses on the creation and optimization of ocular films of prednisolone for the management of dry eye to maximize the therapeutic impact by prolonged interaction at the corneal surface.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod: \u003c/strong\u003eThe current study sought to formulate ocular Films of Prednisolone for treating of dry eye utilizing solvent casting method. The concentration of Polyvinyl pyrrolidone K-30 and Glycerine used as polymer and plasticizer, respectively, in the ocular films were optimized using the central composite design (CCD). Thickness, pH and drug release parameters were adopted as dependent responses. Ocular films were assessed for different physicochemical parameters like film thickness, folding endurance, surface pH, uniformity of weight, drug content, swelling index, moisture adsorption, moisture loss, in-vitro release study, kinetic study, stability study and test of ocular irritation on rabbit eye.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe optimized ocular film (P2) with thickness 0.506 mm and pH 6.8 showed appropriate physicochemical characteristics for ocular delivery. The optimized formulation released 90.75% of the encapsulated drug during 12 h. Release followed Higuchi kinetics and revealed transport mechanism was non-fickain. Tests for stability were conducted on this improved formulation. The ocular film passed the sterility test, and the physicochemical characteristics did not significantly alter between the 0th and 60th day. Thus, it was discovered that the formulation was stable. The films did not cause ocular toxicity or irritation, according to the results of the eye irritancy test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur research leads us to the conclusion that optimized prednisolone ocular film (P2) may help alleviate dry eye by increasing residence duration, prolonging drug release, and requiring less frequent administration.\u003c/p\u003e","manuscriptTitle":"Development and Optimization of Eudragit® L100 Film for Ocular Delivery of Prednisolone for Dry Eye","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 06:17:59","doi":"10.21203/rs.3.rs-7283794/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8de1af36-63c0-4dbd-aa07-930e20f5bf0e","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-12T05:53:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-11 06:17:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7283794","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7283794","identity":"rs-7283794","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}