Formulation and Evaluation of Buoyant tablets loaded with Nanosponges containing entrapped Cefditoren pivoxil | 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 Formulation and Evaluation of Buoyant tablets loaded with Nanosponges containing entrapped Cefditoren pivoxil Naga Raju Kandukoori, Gundegani Saikumar, Deepika B, Katla Venu Madhav This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6419189/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background The main objective of this research was to develop a novel gastroretentive formulation for Cefditoren pivoxil, an insoluble and poorly permeable drug. Floating and drug release characteristics of tablets formulated with pure Cefditoren pivoxil were compared with the same of formulations loaded with nanosponges (NS) form of drug. Results Test results related to physicochemical properties of all prepared tablets were observed to be in compliance with standards. More floating lag time and less log time have been resulted from the formulations with pure form of drug (F1 to F4), whereas, vice-versa was found with NS based dosage forms (F5 to F8). An evaluation test for in-vitro drug release was performed for all the dosage units and more controlled release pattern with diffusion mechanism was seen from tablets loaded with NS. F7 with a combination of NS form of drug and Guar gum in 1:1 ratio has shown best buoyancy and more controlled drug release among all 8 tablet compositions. Conclusions The importance and need for entrapment of an insoluble, less permeable drug to obtain the fruitful buoyant and drug release properties from Gastroretentive tablet dosage forms has been witnessed by all the observed results. Buoyancy Floating Gastroretentive Cefditoren pivoxil Nanosponges Guar gum Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Dynamic and complex ‘gastrointestinal tract (GIT) environment’ is a major challenge for oral route (the most convenient route for the patients), because of its sensitivity towards several factors. Therapeutic success of many oral dosage forms is greatly affected by gastric emptying and intestinal drug metabolism. Having ‘good absorption window in stomach region’ and ‘high metabolism in lower GIT’ will mandate the drug candidates to possess gastric retention. So, designing of gastroretentive (GR) dosage forms for those drugs to overcome the above said shortcomings is necessary. 1 Various formulation strategies followed by researchers to enhance the gastric retention of dosage units are mucoadhesion, floating, sedimentation and expansion etc. The most promising gastric retention of formulations could be seen with hydrodynamically balanced forms (floating systems). 2 Nanosponges (NS) which are nano-scale tiny structures possess a mesh like consistency with entrapped medicament. As they possess both ‘spherical colloidal nature’ and ‘amphiphile nature’ (with internal hydrophobic chamber & exterior hydrophilic branching), enriched solubilization of drugs both in aqueous phase and lipid phase can be possible. Nanosponges are ranked best over other nanoparticles because of their reproducibility in various treatments like washing with eco-friendly solvents, stripping with safe hot gases, mould heating and facilitation of pH or ionic strength alteration. A free movement of drug component can be facilitated by several voids which are consisted in the core structure of nanosponges. A good compatibility with chemical linkers will enable the selective attachment of nanosponges to targets. Most valuable results can be seen with transformation of liquid materials to solid forms. Beneficial clinical results have been noticed in lung and oral drug release systems because of their nano-grade size which enabled them to act as viable medication delivery vehicles. 3 An effective incorporation of nanosponges into topical hydrogels can also be possible. 3,4 Prolongation of formulation residence time in stomach region always offers the best therapeutic benefits for drugs with gastric absorption window. So far, the literature has shown the several attempts of many researchers to fufill this objective. But Biopharmaceutical Classification System (BCS) class-IV drugs, which have less solubility and poor permeability in gastric region are of consideration in this study. More outstanding results like enhanced bioavailability and enhanced therapeutic action can be resulted upon rectification of the problem related to poor solubility and permeation. More convenience can be offered to the drug embedded in sponge like structure to get solubilized in available voids of network meshes. 5,6 This research mainly focused to entrap BCS class-IV drug (Cefditoren pivoxil) in nanosponge structures for enhancement of dissolution. Then altered nanosponge form of drug was used in formulation development of floating tablets. Materials and Methods Materials used in research Cefditoren pivoxil (gifted from Vista Labs, Narketpally, Nalgonda), HPMC K100M, Guar gum, Microcrystalline cellulose (MCC), Talc, Magnesium stearate, Sodium bicarbonate, Citric acid, Hydrochloric acid, Ethyl cellulose, Dichlormethane, Ethanol and Polyvinyl alcohol (purchased from Alkem Laboratories, Hyderabad). Experimental methodology : 1. Drug compatibility in preformulation study for Nanosponges: The possibility of Cefditoren pivoxil interactions with selected polymers and other excipients was checked in preformulation studies to confirm drug compatibility in designed formulation blend. Fourier Transform Infrared (FTIR) spectroscopic method was opted for this study. The generated FTIR spectra for both pure drug and its physical blend with other excipients were analysed to interpret peak regions of characteristic groups. The presence of any deviations with characteristic peaks of Active Pharmaceutical Ingredient (API) in physical blend spectrum was noticed to know the status of drug compatibility. 7,8 2. Preparation of Nanosponges for Cefditoren pivoxil: In this research, API has been entrapped in nanosponge mesh like structures using ‘Emulsion solvent diffusion’ method. The main experimental process that has been executed to get nanosponge forms is a controlled and dropwise addition of internal (dispersed) phase to external (aqueous) phase. The polymeric materials selected for this nano-formulation were Ethyl cellulose (EC) and Polyvinyl alcohol (PVA). EC was mixed with Cefditoren pivoxil at the ratio of 1:5 (drug to polymer) as it has been proved to be best optimized combination with promising results in previous literature. 7,8 A blend of Cefditoren pivoxil (50 mg) and Ethyl cellulose (250 mg) was solubilized in an organic solvent mixture (20 ml) containing Dichlormethane and Ethanol in 1:1 ratio. A complete dispersed phase was obtained by enabling the complete dissolution of EC and drug in solvent blend. A practice of complete dissolution of Polyvinyl alcohol (500 mg) in distilled water (100 ml) was executed to obtain external phase. Then a slow addition of dispersed phase to external phase was implemented during stirring at 1000 rpm using a magnetic stirrer. The wet product was obtained through filtration of resultant mixture which has been previously homogenized for 2 hours. Hot air oven was opted to dry the filtration residue at 40˚C for 24 hours and dried drug loaded nanosponges were collected. Solvent traces, if any from the resulted nanosponges were eradicated by placing them in vacuum desiccator. 7 3. Characterization of drug loaded Nanosponges A) Experimental yield : Experimentally produced nanosponges were weighed and compared with formulation theoretical mass to get production yield using below formula: Practical weight was obtained by noting the mass of completely dried NS forms. The sum of individual weights of both drug and polymer was taken as theoretical weight. 7,8 B) Drug entrapment efficiency: Crushed powder of drug loaded nanosponges (weight equivalent to dose) was obtained by triturating them in a mortar using pestle. Ethanol (50 ml) was used to suspend the resultant for 24 hours and collected the filtrate after filtration of uniformly mixed suspension. Then scanning of duly diluted filtrate was executed in UV-Visible spectrophotometer to get the absorbance at λ max of 241 nm. Then drug’s calibration curve was used to calculated the amount of Cefditoren pivoxil entrapped in NS formulation. Drug entrapment efficiency in prepared NS forms was estimated using below mentioned equation: 7,8 C) Particle size: Aqueous dispersion of prepared NS product was scanned in Brookhaven instrument which works on dynamic light scattering principle to get mean size of drug loaded nanosponges. 7–9 D) Compatibility analysis using FTIR method: FTIR spectra of both pure Cefditoren pivoxil and NS forms were produced. The presence of characteristic peak regions that have been noticed in pure drug spectrum were searched in spectrum of nanosponges. This analysis enabled the prediction of drug interactions with other formulative ingredients incorporated to prepare nanosponges. Disc shaped pellet was prepared for each sample by mixing it with KBr and then scanned in FTIR instrument to get spectrum. 8 4. Drug compatibility in preformulation study for Floating tablets: The compatibility of Cefditoren pivoxil with polymers and other excipients used in tablet formulation blends, was confirmed using Fourier Transform Infrared (FTIR) spectroscopic method as a part of preformulation studies for floating dosage forms. Spectra were generated for two types of physical blends i.e. i) Blend having pure drug, polymers and other excipients ii) Mixture containing NS form of API, polymers and other ingredients. The analysis of generated FTIR spectra for both pure drug and its physical blends was carried out to interpret peak regions of characteristic groups. The status of drug compatibility was known by identifying the presence of any deviations with characteristic API peaks in spectra of physical blends. 7,8 5. Preparation of Floating tablets In this research, preparation of floating matrix tablets has been done using two separate approaches. In one approach, pure Cefditoren pivoxil was used as an API, whereas in other, pure medicament has been replaced with Nanosponge form of drug. Preparation of tablets was executed using direct compression method. Homogeneous mixing of all the ingredients like pure drug or NS form, MCC, rate controlling polymer and effervescent materials i.e. sodium bicarbonate, citric acid was done in a polybag. Then lubrication of resulted blend was done with magnesium stearate and talc before compression on eight station rotary punching machine using 9 mm flat faced punches (Table 1 ). 10 Table 1 Formulation composition of Cefditoren pivoxil floating tablets Formulative Ingredients (mg) Formulation Code F1 F2 F3 F4 F5 F6 F7 F8 Cefditoren pivoxil (pure) 200 200 200 200 - - - - Cefditoren pivoxil (as NS forms) - - - - 200 200 200 200 HPMC K100M 200 250 - - 200 250 - - Guar Gum - - 200 250 - - 200 250 MCC 132.5 82.5 132.5 82.5 132.5 82.5 132.5 82.5 Citric acid 37.5 37.5 37.5 37.5 37.5 37.5 37.5 37.5 NaHCO 3 150 150 150 150 150 150 150 150 Mg. Stearate 15 15 15 15 15 15 15 15 Talc 15 15 15 15 15 15 15 15 6) Evaluation of prepared gastroretentive tablets A) Characterization for physicochemical properties : In-vitro methods were applied to perform the evaluation tests like weight variation, hardness, thickness, friability and drug content as per reported methodology in literature. 10 The compliance of obtained results with pharmacopoeial limits was confirmed after their thorough checking and comparison with standards. B) Floating properties : Buoyant properties were predicted in 0.1 N HCl (pH 1.2) medium. Estimation of floating lag-time and log-time values was carried out for buoyancy characterization of prepared dosage forms. A beaker (1 litre capacity) containing 900 ml of medium was used for these tests. A dosage unit was placed in medium in which it sinks to bottom instantly and floating lag-time was recorded by noting the time taken by tablet to float on surface of liquid. The duration of buoyancy for this floated tablet after its lag-time was noted as floating log-time. 10 C) In-vitro dissolution study : Simulated gastric fluid i.e. 900 ml 0.1N HCl (pH 1.2) at 37˚C temperature was opted as medium to estimate the percentage of drug released from floating matrix dosage units. USP type-II (paddle) apparatus was used for this in-vitro testing. The speed of paddle rotation was maintained at 50 rpm. This dissolution test was performed up to 12 hours & the periodic time points to collect 5 ml sample during study were at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12-hour. UV-Visible spectrophotometer was used for scanning of collected samples at λ max of 210 nm and absorbances were recorded. API’s calibration curve was used to calculate the cumulative % of drug release at each time point with obtained absorbance values. 11 D) Drug release kinetics and mechanism : Fitting the obtained in-vitro drug release data into different equations of zero order, first order and Higuchi, Korsmeyer-Peppas, Hixson-Crowel models & plotting the relevant linear curves, has enabled the confirmation of release-kinetics and release-mechanism of medicament from polymer matrix. The obtained regression values (R 2 ) of every straight line were compared to select the best fit linear curve with highest value and that selected respective model was used to explain the drug release kinetics and mechanism. 10,11 E) FTIR analysis of best formulation for drug compatibility : FTIR analytical method was opted to check the possibility of drug interaction with other excipients in selected best formulation. The dosage unit was converted to powder by grinding it in a mortar. The ground tablet powder was mixed with KBr to prepare it as disc shaped pellet and scanned in spectrophotometer to get spectrum. The characteristic peaks of pure drug (as found in API spectrum) were verified in resulted spectrum for their presence and deviations to confirm the status of compatibility. 10–12 Results 1. Drug compatibility in NS preformulation study: Fig. 1: FTIR spectra of i) Pure Cefditoren pivoxil and ii) NS formulation blend 2. Characterization of Drug loaded Nanosponges A) Practical yield, Drug entrapment efficiency and Particle size of Nanosponges: The final weight of yielded nanosponges has indicated 6.76 % of practical wastage. After experimentation, the obtained experimental yield of NS formulation was found to be 93.24 % w/w. The resulted nanosponges have found to be well entrapped with drug and entrapment efficiency value was 93.66% w/w. B) FTIR spectroscopic analysis of NS: Fig. 3: FTIR spectra of pure Cefditoren pivoxil and Nanosponge formulation 3. Drug compatibility in floating formulation blends: Fig. 4: FTIR spectra of i) Pure Cefditoren pivoxil and ii) Blend with pure drug iii) Blend with nanosponges 4. Evaluation of floating tablets A) Physicochemical characterization: The noticed results for weight, thickness, friability and drug content of all formulations were converted to get mean ± SD values through minor calculation. All these results are represented in below Table 2. Table 2: Results for physicochemical characterization of floating formulations Parameter Formulation Code F1 F2 F3 F4 F5 F6 F7 F8 Weight (mg) 749±0.86 747±1.03 751±1.27 750± 0.56 749± 1.01 752± 0.88 748± 0.91 749± 1.34 Thickness (mm) 4.6±0.03 4.5±0.04 4.5±0.05 4.4±0.07 4.5±0.09 4.4±0.11 4.6±0.04 4.5±0.06 Friability (%) 0.88±0.07 0.74±0.16 0.63±0.09 0.81±0.01 0.54±0.18 0.69±0.04 0.59±0.12 0.79±0.05 Drug content (%) 98.9±1.42 99.6±1.19 99.2±0.87 98.8±0.74 99.3±1.54 98.7±1.07 99.7±1.44 99.4±1.24 B) Floating lag-time and log-time: Table 3: Buoyant properties of floating formulations Parameter Formulation Code F1 F2 F3 F4 F5 F6 F7 F8 Floating lag time (min) 11.2±0.52 9.6±0.84 8.6±0.46 6.4±0.32 5.6±0.19 3.6 ±0.24 2.1 ±0.22 1.9 ±0.54 Floating duration (hrs) 7.7±0.46 8.9±0.74 9.1±1.08 10.4±0.53 11.1±0.39 >12 >12 >12 C) In-vitro drug release: Table 4: Dissolution study data for floating tablets Time (hrs) Cumulative % of Cefditoren pivoxil Release* F1 F2 F3 F4 F5 F6 F7 F8 0 0 0 0 0 0 0 0 0 0.5 0.91±0.14 0.89±0.11 0.87±0.31 0.74±0.02 1.24±0.14 1.06±0.04 0.97 ±0.21 0.86±0.09 1 2.89±0.17 2.45±0.99 2.32±0.29 1.98±0.19 4.36±0.31 3.97±0.61 2.82 ±0.19 2.16±0.31 1.5 3.44±0.24 3.15±0.34 3.21±0.16 2.96±0.21 8.76±0.28 7.11±0.79 7.11 ±1.02 6.49±0.82 2 6.63±0.45 5.97±0.79 5.44±0.83 5.09±1.01 15.84±1.19 13.29±1.03 12.36 ±1.09 11.29±1.76 3 8.29±1.09 8.03±1.04 8.12±1.15 7.49±0.87 33.73±1.57 28.66±1.09 27.66 ±1.29 23.89±1.34 4 15.45±1.34 14.29±1.44 13.97±1.27 11.68±1.19 44.76±1.82 36.99±1.29 33.63 ±1.67 31.19±1.67 6 35.24±1.23 32.22±1.23 31.43±1.33 29.87±1.24 62.19±1.49 55.12±1.41 57.19 ±1.37 53.66±1.61 8 49.77±1.42 46.47±1.45 44.53±0.76 38.87±1.09 76.39±1.67 67.41±1.49 72.19 ±1.88 69.34±1.52 12 69.89±1.52 63.88±1.37 59.75±1.37 46.39±1.87 88.12±1.83 76.27±1.58 99.77 ±1.13 91.74±1.84 *The representation of all values was done as Mean ± SD; n=3 D) Kinetics and mechanism of API release from floating dosage forms: Table 5: R 2 values for drug release kinetics and mechanism models Formulation Zero order First order Higuchi Korsmeyer-Peppas Hixson-Crowell R 2 R 2 R 2 R 2 n R 2 F1 0.9815 0.9669 0.9254 0.9863 1.3975 0.9765 F2 0.9811 0.9727 0.9272 0.9889 1.397 0.9787 F3 0.9797 0.9772 0.9319 0.9909 1.3906 0.9804 F4 0.9534 0.9625 0.9312 0.9876 1.378 0.96 F5 0.9303 0.9964 0.9789 0.9527 1.383 0.9877 F6 0.9292 0.9834 0.9755 0.9561 1.3878 0.9704 F7 0.9877 0.7861 0.9786 0.9728 1.504 0.9287 F8 0.9844 0.9552 0.9772 0.971 1.5414 0.989 E) Drug compatibility in F7 formulation: Fig. 7: FTIR spectra of pure Cefditoren pivoxil and F7 formulation Discussion 1. Drug compatibility in NS preformulation study: All the characteristic peak regions identified in pure Cefditoren pivoxil at 3304.17, 3074.63, 3061.13, 3724.67 cm -1 (>N-H stretching), 1629.90, 1606.76 and 1591.33 cm -1 (>C=N stretching), 1348.29, 1334.78, 1303.72, 1284.63, 1253.77 cm -1 (>C-N stretching) were noticed in spectrum of NS formulation blend (Fig. 1). These API peaks were unaltered in blend witnessing the absence of medicament interaction with other additives. 2. Characterization of Drug loaded Nanosponges A) Practical yield, Drug entrapment efficiency and Particle size of Nanosponges: A good API loading in sponge-like matrix of polymer present in formulation, has been witnessed by this result. The mean size of prepared nanosponges was less than 1 µm. In size and surface analysis, it was noted that resulted nanosponges were individual, spherical with smooth surface (Fig. 2). B) FTIR spectroscopic analysis of NS: The drug characteristic peaks seen in spectrum of nanosponge formulation were at same wavenumber regions as those present in spectral graph of pure Cefditoren pivoxil. This observation witnessed the drug compatibility with other incorporated ingredients in NS forms (Fig. 3). 3. Drug compatibility in floating formulation blends: All the characteristic peaks seen in drug spectrum have been found in spectra of both physical blends and also the peak wavenumber-regions were almost seen unchanged. This analytical result has indicated the existence of no interactions among the drug and all other formulative additives used in development of floating tablets (Fig. 4). 4. Evaluation of floating tablets A) Physicochemical characterization: A good compliance with pharmacopoeial standards has been observed in all the noticed results. Hardness values of all developed dosage forms were found to be in B) Floating lag-time and log-time: Enriched floating properties have been seen with NS based formulations (F5-F8) compared to dosage units containing Pure Cefditoren pivoxil (F1-F4). Floating lag-time and log-time were found to be more and less, respectively in conventional formulations having pure drug when compared the same parameters in tablets embedded with NS form of drug (Table 3). Enriched porous matrix formation that caused to more entrapment of CO 2 in formulations F5-F8 might be the reason for their improved buoyancy. A fact has been evident from all the observed results that an enriched buoyancy (less lag-time) could be seen with tablets incorporated with 1:1.25 ratios of drug and polymer in comparison to 1:1 dosage forms. A quick formation of hydrodynamically balanced layer around the tablets due to swelling of polymer in these formulations, might be a reason for this positive result. 8 The tablets having 1:1.25 ratio composition of drug and polymer, have also exhibited more floating duration. The retention of CO 2 for longer time in compact porous polymer matrix formed inside the dosage form after swelling may be the another responsible factor for this enhanced buoyancy duration in F2, F4, F6 and F8 formulations. 8,10 A longer buoyancy (>12 hrs) has been noticed with F6, F7 and F8 formulations irrespective of their polymer nature and its proportion. Enriched cross linking of polymer chains with NS matrix components, might have enabled the formulations to possess these better floating properties. 9,10 C) In-vitro drug release: The percentage of dissolved drug at the end of 12 hrs was noted and compared for all the formulations (Fig. 5). More and comparatively fast drug release has been noticed with the tablets having less amount of polymer (1:1 ratio of drug and polymer). The ability of controlling the drug release from dosage units was found to be more with Guar gum (F3, F4) when compared to HPMC K100M (F1, F2) in formulations designed with pure form of drug. The ability of this natural hydrophilic polymer (Guar gum) to swell more and form porous matrix network might have led to delayed release of drug. 10-12 But, a greater ability of Guar gum to dissolve and fasten the drug release from tablets (F7, F8) was noticed in comparison to HPMC K100M (F5, F6) in formulations loaded with NS form of drug (Table 4). The more compatibility of Guar gum polymeric chains with sponge-like structures that led to enriched permeation of dissolution medium into tablet interior might be a cause for increased dissolution of drug in both F7 and F8 formulations. 11,12 Moreover, enriched drug dissolution and release have been noticed from both polymers (HPMC K100M and Guar gum) when they were combined with nanosponge matrices (F5-F8). But, the same polymers have allowed the less dissolution and decreased release of pure API form in F1 to F4 formulations. As per the literature, this less drug dissolution and increased controlled manner of release may be due to more interlocking of free polymeric chains (without sponge networks) which avoided the permeation of liquid medium inside the tablet. 7,8 More dissolution percentage and best controlled release pattern has been noticed from F7 containing Cefditoren pivoxil in NS form, 1:1.25 ratios of drug and Guar gum (Table 4). D) Kinetics and mechanism of API release from floating dosage forms: Zero order kinetics have been seen with the drug release from tablets with pure Cefditoren pivoxil (F1-F3), but F4 formulation has released the medicament through first order kinetic pattern. It was found to be following first-order (F5, F6) and zero-order (F7, F8) patterns in NS loaded formulations (Table 5). The mechanism of drug release from F1-F4 formulations was ‘Super case-II transport’ mode (Korsmeyer-Peppas model) where the diffusion of medicament has been controlled by swelling of polymer matrix. F5 and F8 formulations have released the drug through surface erosion mechanism (Hixson-Crowell model). The possible reasons for this mechanism may be i) less swelling & improper interlocking of polymeric chains with NS sponge-like structures by HPMC K100M at less proportion in F5 and ii) huge expansion of polymeric (Guar gum at high proportion) matrix due to more permeation of medium into a tablet. 10,11 A concentration gradient dependent Fickian diffusion mechanism (Higuchi model) was observed with NS-based F6 and F7 formulations. A systematic arrangement of both sponge and polymeric matrices as an array, made the drug to be diffused out in more controlled way from F6 and F7 tablets. 7,8 More predictable and controlled diffusion (Zero order and Higuchi model) was found in F7 tablets dissolution. As the cumulative drug release was also found to be more than 99% at the end of 12 hours, F7 was selected as best formulation. A representation of F7 graphs related to ‘kinetic and mechanism models’ is evident in Fig. 6. E) Drug compatibility in F7 formulation: Characteristic peak regions appeared in FTIR spectrum of pure Cefditoren pivoxil were noted and compared with the peaks seen in F7-spectrum (Fig. 7). A good compliance has been noticed between ‘all noticed regions of peaks in pure drug’ and ‘wave numbers of all characteristic stretchings in best formulation’. So, the presence of drug compatibility with other used excipients in selected best dosage forms has been witnessed with observed facts in spectra. CONCLUSION Loading of poorly soluble drug in to nanosponges could greatly enhance its solubility and also matrix forming polymeric chains were found to be compatible with NS forms. More drug dissolution has been noticed with tablets prepared with NS units. Sponge-like porous matrix with more entrapped CO 2 in nanosponge units has led to increased buoyancy in NS loaded floating tablets (F5-F8). Good floating and drug release have been resulted from both the polymers (HPMC K100M and Guar gum) in combination with NS forms. A combination of NS form of drug and Guar gum in 1:1 ratio in F7 has shown best buoyancy and more controlled drug release among all 8 tablet compositions. It can be concluded that the conversion of poorly soluble drug to NS form and incorporation of modified API in floating formulation can result in to a successful gastroretentive dosage unit with more promising buoyancy and drug release. Abbreviations NS Nanosponges GIT Gastrointestinal Tract GR Gastroretentive BCS Biopharmaceutical Classification System FTIR Fourier Transform Infrared API Active Pharmaceutical Ingredient EC Ethyl cellulose PVA Polyvinyl alcohol mg milligrams ml millilitre rpm rotations per minute ˚C Degree Celsius nm nanometres HPMC Hydroxy Propyl Methyl Cellulose MCC Micro Crystalline Cellulose mm millimetre SD Standard Deviation Declarations Conflict of interest: There was no conflict of interest declared by authors. Funding: Not Applicable 1. Ethics Statements : Not Applicable. 2. Human Ethics & Consent to participate : Not Applicable. Author Contribution 1. Naga Raju Kandukoori: Involved in designing of research protocol and wrote the main content 2. Gundegani Saikumar: Prepared tables for all the results3. Deepika B: Involved in preparation of figures and analysis of FTIR4. Katla Venu Madhav: Checked the plagiarism of manuscripts and done required corrections Acknowledgement We, all the authors, are grateful to the management of St. Pauls College of Pharmacy for arranging the lab facilities and timely encouragement throughout the study. We are thankful to Vista Labs, Hyderabad for gifting us the API sample. Data Availability 1. The discussions made for results of floating lag time and log time are supported by the below mentioned reference sourcesa) doi: 10.1080/10717544.2023.2174208b) doi: 10.1016/j.carbpol.2018.05.011c) doi: 10.5958/0974-360X.2018.00720.52. The discussions made for results of dissolution study and drug release mechanism, kinetics are supported by the below mentioned reference sourcesa) doi: 10.5958/0974-360X.2018.00720.5b) doi: 10.1155/2023/4322375c) doi: 10.4274/tjps.59454 References Gloria MC, Juan DR, Achmad H, Monica MJ, Isidoro C (2024) Current trends in 3D printed gastroretentive floating drug delivery systems: A comprehensive review. International Journal of Pharmaceutics 663: 124543: 1-20. Naga L, Ganga B, Krishna P, Swathi K, Naga R, Chinna E (2013) Floating Drug Delivery Approaches for Prolonged Gastric Retention. Research J. Pharm. and Tech 6(7): 706-710. Akash G, Wen-Cheng L, Himansu C, Rutvi A, Talever S, Ramkumar C, Braj ND (2024) Nanosponge: A promising and intriguing strategy in medical and pharmaceutical science. Heliyon 10: e23303: 1-19. Sunil K, Babu LJ, Rekha R (2022) A new perspective of psoriasis: Dithranol nanosponge loaded hydrogels. Applied Surface Science Advances 12: 100347: 1-9. Olivia S, Sreejan M, Gouranga N, Subrata J, Sougata J (2023) Recent advances in alginate based gastroretentive technologies for drug delivery applications. Medicine in Novel Technology and Devices 18: 100236: 1-12. Mohammed J, Mohd Sajjad AK, Mohammed S, Saira Z, Hanan Mohammed HS, Layali IA, Heba RA (2023) Development of apigenin loaded gastroretentive microsponge for the targeting of Helecobacter pylori. Saudi Pharmaceutical Journal 31: 659-668. Ashish YP, Khanderao RJ, Sharayu PR, Ashwini SS, Milind JU. Formulation and Evaluation of Nanosponges Loaded Hydrogel of Metformin Hydrochloride. Indian Journal of Pharmaceutical Education and Research. 2023; 57(1): 53-61. Dalia AG, Mahasen AR, Danah AA, Jenan AA, Rafa SA, Reema MA, Sara AA, Siham AA (2023) Formulation and evaluation of Piroxicam nanosponge for improved internal solubility and analgesic activity. Drug Delivery 30(1): 1-10. Cassiana M, Gabriela CM, Clarissa GB, Jamil A, Marcos AS, Gilles P (2018) Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity. Carbohydrate Polymers 195: 586-592. Naga Raju K, Fasiha M, Ravali K, Syeda WJ, Deepika B, Narsimha Reddy Y (2018) Studies on Influence of Polypropylene Foam Powder on Gastroretentive properties of Floating tablets of Cefditoren Pivoxil. Research J. Pharm. and Tech 11(9): 3923-3926. Adane Y, Chernet T, Zewdu Y, Solomon A (2023) Formulation and In-vitro Evaluation of Furosemide Floating Matrix Tablets using Boswellia Papyrifera resin as Matrix forming Polymer. BioMed Research International 1-11. Latha K, Kishore C, Naseeb BS, Shailaja T (2018) Formulation and Evaluation of Sintered Floating Tablets of Cefpodoxime Proxetil. Turk J Pharm Sci. 15(3): 278-290. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 07 Mar, 2026 Reviews received at journal 27 Jan, 2026 Reviews received at journal 16 Jan, 2026 Reviewers agreed at journal 06 Jan, 2026 Reviewers agreed at journal 05 Jan, 2026 Reviews received at journal 29 Oct, 2025 Reviewers agreed at journal 24 Sep, 2025 Reviewers invited by journal 13 Jun, 2025 Editor assigned by journal 24 Apr, 2025 Submission checks completed at journal 24 Apr, 2025 First submitted to journal 10 Apr, 2025 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. 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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-6419189","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471092404,"identity":"7d38d069-f2d3-41fa-8f98-de8962814846","order_by":0,"name":"Naga Raju Kandukoori","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYDCCA2xAogLMZDwAJGT4YDJseLWcYZAAs4GYB64SrxbGNmxacAG+28fSHlfOq6szZz9jcPBHjQ0PG3v7xQcMNXYMfNINWLVInks7bnh222EJy54cg8M8x9J42HjOFBswHEtmYJM5gFWLwRn2NsnGbQckDA4AtTA2HOZhk8hJk2BgO8DAJpGAR8ucOgmD828MDv4EaZF/k/6D4R8+LWzHJBsbmCUMbuQYHOAF28J+DBgguLVInmFLk2w4dlhy54xnBVC/5DBLJPYl8+DSwneGzUyyoaaO35w/eeNDYIjJ8bMff/jhwzc7OfkZ2LUgXIhg8hgwABXz4FePqoX9AUHVo2AUjIJRMKIAAMFGWH4+4v+kAAAAAElFTkSuQmCC","orcid":"","institution":"St. Pauls College of Pharmacy","correspondingAuthor":true,"prefix":"","firstName":"Naga","middleName":"Raju","lastName":"Kandukoori","suffix":""},{"id":471092405,"identity":"3a0c2ebe-5ff6-4ba6-a716-7261a81bb3d5","order_by":1,"name":"Gundegani Saikumar","email":"","orcid":"","institution":"St. Pauls College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Gundegani","middleName":"","lastName":"Saikumar","suffix":""},{"id":471092406,"identity":"f64a974a-64ee-4af0-b889-f9d4478c7c6b","order_by":2,"name":"Deepika B","email":"","orcid":"","institution":"St. Pauls College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Deepika","middleName":"","lastName":"B","suffix":""},{"id":471092407,"identity":"fde278b4-259c-44ad-826f-3a5f2abae9ab","order_by":3,"name":"Katla Venu Madhav","email":"","orcid":"","institution":"St. Pauls College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Katla","middleName":"Venu","lastName":"Madhav","suffix":""}],"badges":[],"createdAt":"2025-04-10 10:23:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6419189/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6419189/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84790502,"identity":"50e69715-5fd6-4105-a47f-4c9d351d039c","added_by":"auto","created_at":"2025-06-17 11:18:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":170409,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFTIR spectra of i) Pure Cefditoren pivoxil and ii) NS formulation blend\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/81c6d2b99cdb870f1ff06ec7.jpg"},{"id":84790500,"identity":"6d9303b8-9f47-4e70-8d37-bc4b5a8d79ad","added_by":"auto","created_at":"2025-06-17 11:18:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58545,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSEM photographs of Cefditoren pivoxil loaded NS formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/fcfa43dcb2b0a605e896216d.jpg"},{"id":84790501,"identity":"f17efec9-86be-4521-a8dd-daf9c1bbdd1b","added_by":"auto","created_at":"2025-06-17 11:18:23","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":101503,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFTIR spectra of pure Cefditoren pivoxil and Nanosponge formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig3.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/dc81a2ede7344aef56b7805d.jpg"},{"id":84790504,"identity":"81b79e8b-7997-4077-a5a0-18eb22aacb0d","added_by":"auto","created_at":"2025-06-17 11:18:23","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":156413,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFTIR spectra of i) Pure Cefditoren pivoxil and ii) Blend with pure drug iii) Blend with nanosponges\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig4.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/5420d49de6a599edb32dcd17.jpg"},{"id":84791846,"identity":"d1a79cef-1b60-41a4-b417-603ddfa30ff2","added_by":"auto","created_at":"2025-06-17 11:34:23","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":74841,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIn-vitro Drug Release Profile of Floating Tablets\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig5.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/82ad6fc4df5b86396ac6f0d2.jpg"},{"id":84790508,"identity":"e28767d2-70f5-4a72-9126-36c42dea719d","added_by":"auto","created_at":"2025-06-17 11:18:23","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":164496,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDrug release data fitting into kinetic and mechanism models (F7)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig6.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/149276d5d8df1de53c0c3e95.jpg"},{"id":84791562,"identity":"6d4de65a-97c8-4c6d-96ee-317d0cca0fbc","added_by":"auto","created_at":"2025-06-17 11:26:23","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":145859,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFTIR spectra of pure Cefditoren pivoxil and F7 formulation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig7.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/fcaaf201009bca667c674add.jpg"},{"id":84793082,"identity":"1d7498a5-7048-484f-a9aa-18e13ed76ca4","added_by":"auto","created_at":"2025-06-17 11:50:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2923261,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6419189/v1/eaf62a87-3e7b-48d4-ab17-a9f44307d02b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Formulation and Evaluation of Buoyant tablets loaded with Nanosponges containing entrapped Cefditoren pivoxil","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDynamic and complex \u0026lsquo;gastrointestinal tract (GIT) environment\u0026rsquo; is a major challenge for oral route (the most convenient route for the patients), because of its sensitivity towards several factors. Therapeutic success of many oral dosage forms is greatly affected by gastric emptying and intestinal drug metabolism. Having \u0026lsquo;good absorption window in stomach region\u0026rsquo; and \u0026lsquo;high metabolism in lower GIT\u0026rsquo; will mandate the drug candidates to possess gastric retention. So, designing of gastroretentive (GR) dosage forms for those drugs to overcome the above said shortcomings is necessary.\u003csup\u003e1\u003c/sup\u003e Various formulation strategies followed by researchers to enhance the gastric retention of dosage units are mucoadhesion, floating, sedimentation and expansion etc. The most promising gastric retention of formulations could be seen with hydrodynamically balanced forms (floating systems).\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNanosponges (NS) which are nano-scale tiny structures possess a mesh like consistency with entrapped medicament. As they possess both \u0026lsquo;spherical colloidal nature\u0026rsquo; and \u0026lsquo;amphiphile nature\u0026rsquo; (with internal hydrophobic chamber \u0026amp; exterior hydrophilic branching), enriched solubilization of drugs both in aqueous phase and lipid phase can be possible. Nanosponges are ranked best over other nanoparticles because of their reproducibility in various treatments like washing with eco-friendly solvents, stripping with safe hot gases, mould heating and facilitation of pH or ionic strength alteration. A free movement of drug component can be facilitated by several voids which are consisted in the core structure of nanosponges. A good compatibility with chemical linkers will enable the selective attachment of nanosponges to targets. Most valuable results can be seen with transformation of liquid materials to solid forms. Beneficial clinical results have been noticed in lung and oral drug release systems because of their nano-grade size which enabled them to act as viable medication delivery vehicles.\u003csup\u003e3\u003c/sup\u003e An effective incorporation of nanosponges into topical hydrogels can also be possible.\u003csup\u003e3,4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eProlongation of formulation residence time in stomach region always offers the best therapeutic benefits for drugs with gastric absorption window. So far, the literature has shown the several attempts of many researchers to fufill this objective. But Biopharmaceutical Classification System (BCS) class-IV drugs, which have less solubility and poor permeability in gastric region are of consideration in this study. More outstanding results like enhanced bioavailability and enhanced therapeutic action can be resulted upon rectification of the problem related to poor solubility and permeation. More convenience can be offered to the drug embedded in sponge like structure to get solubilized in available voids of network meshes.\u003csup\u003e5,6\u003c/sup\u003e This research mainly focused to entrap BCS class-IV drug (Cefditoren pivoxil) in nanosponge structures for enhancement of dissolution. Then altered nanosponge form of drug was used in formulation development of floating tablets.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cstrong\u003eMaterials used in research\u003c/strong\u003e \u003cp\u003eCefditoren pivoxil (gifted from Vista Labs, Narketpally, Nalgonda), HPMC K100M, Guar gum, Microcrystalline cellulose (MCC), Talc, Magnesium stearate, Sodium bicarbonate, Citric acid, Hydrochloric acid, Ethyl cellulose, Dichlormethane, Ethanol and Polyvinyl alcohol (purchased from Alkem Laboratories, Hyderabad).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eExperimental methodology\u003c/b\u003e:\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1. Drug compatibility in preformulation study for Nanosponges:\u003c/h2\u003e \u003cp\u003eThe possibility of Cefditoren pivoxil interactions with selected polymers and other excipients was checked in preformulation studies to confirm drug compatibility in designed formulation blend. Fourier Transform Infrared (FTIR) spectroscopic method was opted for this study. The generated FTIR spectra for both pure drug and its physical blend with other excipients were analysed to interpret peak regions of characteristic groups. The presence of any deviations with characteristic peaks of Active Pharmaceutical Ingredient (API) in physical blend spectrum was noticed to know the status of drug compatibility.\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2. Preparation of Nanosponges for Cefditoren pivoxil:\u003c/h3\u003e\n\u003cp\u003eIn this research, API has been entrapped in nanosponge mesh like structures using \u0026lsquo;Emulsion solvent diffusion\u0026rsquo; method. The main experimental process that has been executed to get nanosponge forms is a controlled and dropwise addition of internal (dispersed) phase to external (aqueous) phase. The polymeric materials selected for this nano-formulation were Ethyl cellulose (EC) and Polyvinyl alcohol (PVA). EC was mixed with Cefditoren pivoxil at the ratio of 1:5 (drug to polymer) as it has been proved to be best optimized combination with promising results in previous literature.\u003csup\u003e7,8\u003c/sup\u003e A blend of Cefditoren pivoxil (50 mg) and Ethyl cellulose (250 mg) was solubilized in an organic solvent mixture (20 ml) containing Dichlormethane and Ethanol in 1:1 ratio. A complete dispersed phase was obtained by enabling the complete dissolution of EC and drug in solvent blend. A practice of complete dissolution of Polyvinyl alcohol (500 mg) in distilled water (100 ml) was executed to obtain external phase. Then a slow addition of dispersed phase to external phase was implemented during stirring at 1000 rpm using a magnetic stirrer. The wet product was obtained through filtration of resultant mixture which has been previously homogenized for 2 hours. Hot air oven was opted to dry the filtration residue at 40˚C for 24 hours and dried drug loaded nanosponges were collected. Solvent traces, if any from the resulted nanosponges were eradicated by placing them in vacuum desiccator.\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003e3. Characterization of drug loaded Nanosponges\u003c/b\u003e \u003c/p\u003e\u003cp\u003e \u003cb\u003eA) Experimental yield\u003c/b\u003e:\u003c/p\u003e \u003cp\u003eExperimentally produced nanosponges were weighed and compared with formulation theoretical mass to get production yield using below formula:\u003c/p\u003e\u003cp\u003e\u003cimg 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\" width=\"469\" height=\"70\"\u003e\u003c/p\u003e \u003cp\u003ePractical weight was obtained by noting the mass of completely dried NS forms. The sum of individual weights of both drug and polymer was taken as theoretical weight.\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003eB) Drug entrapment efficiency:\u003c/h3\u003e\n\u003cp\u003eCrushed powder of drug loaded nanosponges (weight equivalent to dose) was obtained by triturating them in a mortar using pestle. Ethanol (50 ml) was used to suspend the resultant for 24 hours and collected the filtrate after filtration of uniformly mixed suspension. Then scanning of duly diluted filtrate was executed in UV-Visible spectrophotometer to get the absorbance at λ\u003csub\u003emax\u003c/sub\u003e of 241 nm. Then drug\u0026rsquo;s calibration curve was used to calculated the amount of Cefditoren pivoxil entrapped in NS formulation. Drug entrapment efficiency in prepared NS forms was estimated using below mentioned equation:\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e\u003cimg 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CaLW0gTuUsRI7JPJR/v6EVqe/ftB3uQ23F+cR4Lc7xrS2CYYz3ve82KSoA2kSwZ9mSIx2oR8uF2l1e93CKQJjueHZeK4LxNkiOsOuZWn/uJdQkSB623rrbeOCQzij+hoJy5H7xsXrAmaPrf//vuHG32qIQlQIjHJaAO7QWw8GKTaQAUUjoGG5WGvvfYaC9Zsg6PZvgEJQQCDsziK/uDYtx609FseLAVmof3nxRCw9viU28zvta99bcxCoa+cpNFXXn0gTRTmMccc022zzTZjs+D2vOf8Wjlamfrp9a8hG+IhyKMBITTwqwOZGuRbXT1j4B9WpsPpt+ue9esrnT7kow5m3w1kJo3+DNjxeDIBFguxUE05NTm0fD0/nIZ71aXVTZn7REFbax9fFwp+pqQpcm03Cv08pK1erBeskU15AlLEYsOqgABTgP5KH5THj+LtL1yoXH6usWixaOiTDUiBODYWINaKecljGK3sfg3jHffP9SH94Wu+/DLJEEulPKBMLB3ud54103PDZXO9oeVLJvqlmB8Es0GflQ6Ziw0Sw+b9lY8YNrFk5CbWpm+N1O9ZeshLWyOT4rYakKJmierLElqZ2rH+ogxiEVlPkSuxfy2Ox0RHILprDYiQ8iJHSBZZIbGIkZiuqYbx3+BEInGrYADxJQhyMAoGSpYX5MNACQYrs1ABpgY95niDHTM66w0Li9mpAF8uMsHUBk8DpQHY88z7gpidZ8kQQNqIBJLieSTL8wY293lWOSyaZyZokOYqMYM36FFi0nKuP8ttkL4BXBBp+1qFkvS/cguclU6zPvlL4bbZJHKhHOpK2c+aNSssCWbhnvc1FlmwRlCwlAO3ATInD1+FeV6eFLg0lJOCAbJ2XZsAebFQkRPZ9gd/EPjKUkARSp+SEUjq/LOe9ay4R9rab7wZMSX00pe+NGRh5q9MysciQuFwbwhG9+sTikZQkIh+H9AvWF/8rD9EIbLeIbHt655R0C76oXKSM6LExcJ61Nx5+gIypF+5X5lYArgkXWPJYhXSbvoO6wlXGLAcyhvJIWPkAiFznzz8r60pa25EMneOYlUHdfcsefYJGZCvZ70fTdH3j/3IUd9V5lFQb9fa84B0IPzIuv7SoJ/pp96BFtyNiJN561PeAZAmeehTSJL6yosFSd28w95F+bDmsLxwObtmYuMZbYeoaF/3ykNeLDXeAZYX1hlWZH1RebxLAuYt3IjMKJN2bfXQ17W3+6RHNqeeemqse6W/kAMrs/KB/qxM3KDa1Q+RQ5q0DbKmzsrinXPvVEN+BZZITBKQEMSCi8LgZhAx+HBRmCE3UDZmWgZRCsYXTSw8BhiKw+C1xRZbxNcoFCIfvfgRgyeCQiExY1vrxGBKqVNYSIhBzQDoCyTloaB8vSEPM/r2vLgDzysXwiFfZMDzBj3kgzWKZYeSonwoRvn2YzMQKM95Xjnk5Wsg8Rn+mnEaqJHBZmVCzCh4yowyRTSaLLjQlBUJ4K5QJzFAXAdkaiBGYHylgxggK0iY/LhamgtRWSkDysxXN5QspSvGimJAoFh0xG40CwuQp/wpk2OPPTa++NE2vjiSNwUhRgZZkCa3BjcUN1IfYiqco/jkpR3JdP311w+yQKlpH22h7GLAWt3Ey5CdtqAgPWudIeQPiWLBQaTIFKlFVHxNpZwN+pC2Y8mShr9kKz5HuRApCk+ZXvWqV4XSk7+2ooQpefkjBc6Ts6/slBmpUwbPyEfZpOuLQn1gzpw5UTZ9jHIlUzEl2p87xnV9Ud7awK//flDU4tWQCjKWvzL630/7qg8yoG76EitHS8Pz+r/6IRXKot+268qjLvoNuSGsZKJc3lf9HrnyPrLkaSvtrR/pp77U1FfdSx7eIwR59uzZnS+5EIwDDzwwYsCURRt779RdWUxm9Dv9U3yg+unr5I6Ysb55J5EfljmyRqIQal/zIUDy1Sb+6ivaQb9BcMjN2EOG3hF9Vr7eY6RffJc+rt/pj+pFluQib+1ENs6Jm1Jf7lduMJOQqYTcCiORWIDwehlgE4sn5td+E2nfyeoDyCCrAwLdBwVNAbfYjonitpTr9nr21mBh5jevvIavIbOsZj4xR0gmu4yIl/WHWCP7MCkRhL7lllsOzswbC7u9FibSBZZILEBM1YFjumB+7TeR9p2MPmCmL8DYDF7sCisaS4iZPcuG2fwtxW0p1+317K3BwsxvXnkNX0MsWLRYBCe7jFyKrDesP1yVrb8gRSypLHYTxcJur4WJtAAlEonEIg4KTQwNtw63FLcdlxfXD1eLhfMSiw/E3HHtcj8JduYWYw2aLFDryDGXHEuT/iJuiMtPf+FSn8rEZqJIApRIJBKLCcRiiWESnyKgV1xQP34msXigxZCJ9WHdE2vUj+GaLIizal906S9i9sSZJeYiCVAikUgkEolph4wBSiQSiUQiMe2QBCiRSCQSicS0w3xdYPyTFqWyRgDwJXpEAJX1QPif28qTCxPWUFAmeStjvxp8ndZWuD3KtajD+ib8wmQksFJ7NmhT7dmPKXC/9TGsu8Jvvccee0TwnrUpLGpmzRnrZliPA6wvMj9YN8aaJBbzE8SZSCQSicUfdAudQb+ABR+tz+VY/Jr1isBfC382XjEK9DpYbXsY1quyJhMOMmptovldb5gvQ7Co03Of+9xYIt5PBLkFsig9izZRiBYdW5igtC0IZS0DQV0WhFKmVq62hPhE4fPA4ZVIF3cgiKNgMa3NNtssFtmyFHqTm5+FyxATn0w2+OrEKqlWK0V8rJRqCwUrjCJGFoiz2J42Ecg3ESBYVocd1bETiUQisfiBEeJtb3tbrElFF/jq7OlPf3os1AjvfOc7QzdbWdpCr/1V0PtAlCz3YCXsUdtv+ILO6tvSwAN86t8HfWStLNdxFDpvXLAAzQ+VxZWtttqqPOIRjyh1xh/nKjsrH/7wh8saa6xR7ne/+5VPfvKTcX5hopKvUoVZfvOb3wzOzEVVzuVLX/rS4GjeqGy1HHnkkaUy18GZxR+1w5VKXAZHN8eNN95YllhiifK85z1vcGYuKhEsJ554Yvn5z38ex5VBl0qKynHHHRfHDZUkle23335wlEgkEonEXFQCUirxCR0ze/bswdm5nGGvvfYqddJc/va3vw3O3hxXX311qZPrcqc73amcfPLJg7Nzcd1115WNNtqoHHHEEXH8wQ9+sDzmMY8pdWIex3Xif7Pr66yzztj1YUzIR8SVZKl25ix7jwCTFquBJb6tMWCZbO6QhQksk+Wmlalh5513nvC6GJa6tzhUf3n/xRlMf0cdddRNXFvDaO5B7dmHZex32GGHsM4AJm5JfJ9q9mEhtmbKTCQSiUSige5lCbJ9hr8+9wdbgdg2xh5p89K3D3zgA8P6M6x3wBY5trSxpx3YaZ8rTT4w6jq9Ju9RmHCQzLCybHj4wx8ee+NYnMtS7Vwv9vuxqJP9auwTY8ltwrBXDLIB9kLxLALVYB8TJit7w6y55pqxWJNddO1hMoxK3oL8iFvpu1K47PgOVdp+LpYZZw6zhDyh2KPH/ivAhXPwwQfHglHKYy8X7jyuHquuWmLeeTErlhQnTA34jGc8Y6xMrrlPPvY04l7yDJcRkIc9eRAL5WG6U28Nwldqo0WysVx53/Vkbyeb4qm/ctvTBZRD+azy+dGPfjT2idpuu+0iHzE6iKgNIpXHPjzaZRjN3TccI2VvG/Lks2WC5FpEdpSf65M5klmRjJgdtZMNG3Xw/fbbLzawbEBKucnsXM0kap8a+Wob+/iom4XdGrSbPXXUV9+x1442tteSeuhL4pDI6oADDgii18AkKn9tQxbqYe0L+w+tscYaseqptgH7dOlX6tGH1VjtN9X2Jhr1s79PIpFIJOYNJIZu4/6y+z3dQUcJp5lIbG5/fG8wqbdBrT3o2iSd8UVe9ASdg1+sssoqN7subGOkUSDsQBPAPvvsE+6uqhAHZ/6HSihEIJeqIMoNN9xQNt9887LccsuVc845J5573/veV84888xSC1MqMYhnqiIvleGFuwoqQSmVOZYqqPKnP/2pHHbYYaUyu/LZz362/Pvf/457+qjKtFQmWSrRKWeddVapCjJ+lSyUqqDjHuawZz7zmaUKoJx22mmlEqxSiUi4zbi8mOTcX8lWlPvPf/5zqUo5rldlXCoJir/SXX755cub3vSmMN1VJRtmNaiKulSiUNZff/1y+OGHl1NOOaU88pGPjHKp47XXXhuuJsfMepVslZ133rnc5z73KZU4lbPPPjvOu/7mN7850qxkIJ7xLLdUJR+RfiU4Y2VxXb3PP//8svLKK5dKfEImlZCV1VZbLdJWR+7LYThXSWOYCpvcKmkqlcBEnlA7S5gyK1kLkyXZ1E4ZaVYyEC5R7USG+oS+QdYg/d12261UchnPnXHGGWXppZcu5557brgclXvZZZcNFyrI5znPeU64MisJjP5TiXOkX4le9INDDz007mdSnTFjRrQNaGuy+cIXvhBtWMlSqS9A5Ov+pZZaKurV5FBnB6WSn+hviUQikVhwqJPWsuSSS5aNN954cGZiMH7TGX0XGN1A13KvCeMAOk9IBnfbb3/727LZZpvd7Pquu+4a1+nuYUx4IcR99903dh62u7Lg2T5YUGzmxhJk92MWirbtfrPO+J8lgNXClz+sBmbsRx55ZGy7z5LAGuPrIsHNLAB2lmYpGZ6tg2JbPtwuuqwTrBbgOYG7bW8cQdpVOcZ+KJgnpsjCwEzGheY6qwoLAbeenXRZVVgj7CgMgqQtKe6cKHcWEUuYSxP23nvvSM/uuVbZZK1hZeCKYwVhTbKzNCsUsKAoM7MdNyLYlZflCGvea6+9Qj7KAcqv3KwuLGPulXazuCgXl5Rdfu3kLZhZW7AGjQJLjMh4QWpkDJ4nj9e85jVjO1urh6BygdH9DfWUU0B833pnd2Wsu5LeYOEsXvqAnYVZV9RfWvoA6xZLmb7inB2IWaraZo6sa6xYrFDK6Z7WD5Td7urkdsghh3SVYEe72qGa9YpVyXPajgmVZUhAvPTUT5l91agPmB00mD24ZpYyHsw8WnvNC9rr0ksvHRwlEonE4g3jOG+OMfCWgA6gY+vkNrgDnjAR0LM+cOJNwj2Ah4SV3nhfJ9ERyoEH2B2fjqX76EV6oH+9TsYjAJuHZNj1NmEX2LwgmhvRoZxBpj5v67umKK4+hnkX15Rl3ZEssH8JBc2cNR645XzNZLv+M844I37nnnvuTZ6Rj6+OWsyK//vlamjl8ZcAKcsGil0jcjudffbZ0Th9M55nRLa3JcbFS6266qqxZD0opzQbmOI838rheb/m5mrK0zlyQxg1IGLYzHh9/ygZ9JX5RMD9hvw0uekwTJX9T+BvCZS1QRS+8nlpgCyljfzAcF+47LLLQj6tvgicDt2vb5NVk5v6upfMVl555TH5crnJq8kHQfIVG3KI5CDiyOl48mptMeqXSCQSiYnB2PyRj3wkjBx0osnoVVddNbh6y8FAMd42HibtxvxmCBkGHd7X2WOoA/uEUFnYSBcY99SGG24YX4K1a9xKXCd91Fl4uLy4tECkN1dGc/tAneVHRHdliWXLLbcsH//4xwdXbo6q/MIFJl9un2G4Dlwxa621VrhvoLm4momsXefygdpA4ULqm94qGYuvobhjuIje/e53xxdxDS9+8YvLTjvtNDiai0ouwtUFzIDcew3f+MY3SmW35ROf+EQcK+t6660XbiDYYIMN4su0PsiZq+iaa64pq6++ejnhhBMGV+a6J2fNmhX/k6vrvuYaD/LjjuTKG4XmLqodONyDJ510Uhw3PP7xj7/Zs9ps6623jv/JiYzJrYFJ8+KLL47/K+GJdqsvRxwzj3JT9aGM3FQXXXRRpMXV10C2xxxzTLQZt9vMmTPH2huuuOKKaMcGXwToj9xmXKutLyQSiURi8iGcwVfawjngggsuCP2PG9Bl84NQi2EXGL0kFIJ+oweBDsAVhDW4bnwfvv6MZzwj3GJ9HdEwYQuQoCQMqm8huO6668J9JTCJO6a5xszGa2bxf4NnnauKMGb1XDz+Z5ZyzIXE9VEVdwRMCVblVhkP8mBZqXXollxyycHZubAAEjcYsERJv1kQhsvGEqBunmFia/cJ1m3g0uC+qsQkGKZgZhYlrhRlkB43S7MyceewOgj+BueVs0GZHDerhb/uacfcY5V0hDvJAoPMh4KIsVjPtro3+F8dQPkdk606+TuMls8oKwh3YLPCud5k3IfjVtdRYFliYXrlK18ZVjBfkonO9xda/RtYuLgYuaDUl3xZvLD6tqDWMKQvHe5A1iuyUl/9iBWQ+bOBS1HeysNC1No4kUgkEpMLup3lvU7ox7xCrPr0Osv+8ccfP2bZHw90Dx3Rt9r4X5r0Lc4BvA30LR4y6jq97Tod0PReH3d8RcXg/5FQGcoIoRALQ+lIVJyFGBYFEIujwiBOpW3BL37DVzgICkUmNqQpQkqO60MsCd8ihWpRPcps9uzZ4WryJRW/HvdYXxFSymI+3Kd8/HrKJC5HxZGopjzF4CgjfyIgFu5DcHyNRcjcI+omXdfEI/mkn7+TGwZJc+6iiy4KNwpyI9bE537cbeKWxLWog/gen9aLbxI3c+GFF4Yfs5VBWZEZ8kOgmAYRDvJ1rK7iY3zZhARaxImcfEHHrSZtMvKV0worrBBmRh1K/gio5xE2/lYmQfL1RVyDcrhf3JZ66Wjq7Kcc8pw5c2a4+XxJ5ostMTxIg7KTOVmIlUIGuf5E2HNDIjtir9QdWdM/lBU5VDdxScpttWh5kaW2Vzftp031H/X11ZXofS8NGSirNtW+8tKptc3mm28eBFHsEvLmS0Rf6fWXQWhmUYQdUR+PVCUSiUTi1oFONd6LyTEWmwj7AheM0XR6m2DTrxZFbPGmfdBldAE9Rke4j64DYTLIk8kynS0/ManiYI3rdCw9LC/XzzzzzNAvYoNGjfvzDYKmYClT7AqDohgxLIlRyBTuSiutNLi7i2Bd5AdRYi0SNEoZgs+TkRqxIawcAqQ8i4hQqJSra5SlYrFqyFuwbAtqBkQFyZGHHytHs+ooI8VPiSsH5eseyvuhD31okBj/u7+VTWC2+gk69ok8SwIhIkCUqfxavQRxIS2IHAuVewRBI3Q+8RMPhfQJ3EUupEe5KwNF7NNsZEP6rBjIAhmrszJ5lmyUgeLXUXQilgtEhDxa+XQKdUEGlB/RUQaB4PJFIhCMPhA0HRAplYb2bJCGzibYuLW7NtThyJQFrH26rn2ctxInmSI/zpGxz+cB+UNmlJMckSiElbybZcm9iJv6qy9ySUYCopFf1pyWl7RZiBAZspKu/D3L1+y8MuqTw0A61dfLmUgkEonJBX1NL4rzofvE6/iABoz7yAi9YzxHbFj+LWsyDPrRRJbukaZ7WJAajP2MDj5cwh2sNt0nN/O73seEvwJbkKAMfbVj1r7jjjsOzs4Fi8Qmm2wSxGBRBQLEQsFSllh04EUArk1rQSHYCGMikUgkEosEATIz58pgsmLKYsnA2CwyyELk0zeMclEDBauMrC4sF0x2rGKpZG9/INWHHnpouNBWXHHFiP9hLUokEolEAuYbA7QwwPXCRcJF1NYP4tayKjQXieuLIvg8xblwZfkU26rJ3FX9T+gTtw/0GcSaCdU6Q5ZWTyQSiUSiYZGwACUSiUQikUgsTCyappVEIpFIJBKJBYgkQIlEIpFIJKYdkgAlEgsZvkqzPINlIRZVWC7Bmh23FZZsuOSSS2J5iMUFPtG1i7XPcRcELNsg1pFswBeklpfwqXBi6sEHGdrXlkPavb/I7u0FcauWZ+kv4DsdkTFAicQkwea4Fmk0wFmPyteAXi+DDVgY1BeD1l7ytaOv0iz+uShC+ayq3VZUvTUw8PsyUhC6uvoSrw8EwPpM1g3x1Sc5GYzJztef1n1qq68vTPiYwcJp1r5S/smE9bJ8OGGxWIuMWvNK/a0HZsFUG0knpg58KWwjZwsBIrjWt7GZtg98bk+YfB1wwAHxv8UEF/Y7tqggLUCJxCTBQplIgwUyrU5KwVGgFs90zozLqtk2Y7Vo46K0JYfFKfuwLpcVu28LGpGhBEZ9yan+Fji18uvrXve6IEzkZNNcRMHy9pa2tyr6woQVyJVtQXx9anE37U82LX2r25533nmxAGliLvTHto7X4gyL8dlpwI7kbdNupPf2hj5uQmbCsah+Zb0wkAQokZgksFgce+yxYe2wdpVVtS3uud1228U523Wst956MfAsSuTn+uuvj+1R+rDNyKhVWm8JDKzLLrvsuOtiOW/1datzu89qr+S0ww47xI7+tq2xyjhrjDIuLFjBdkEtZWGmTa7NOgisX5brR4QScy2Dxx133JRQzMh72zYIrMxv94DbG8qjjyPi0xmLxDpAicRUwHLLLTe27Qt3jv1obIFijSsLedr3xjYqgChReqwBlm23CKh92/oDktgZe7axhtgiRloN3G3M6bY9MZghVWCrENe44TxnKxL5cucww9uDjvnbkvTLLLNMLOS5//77xz591rKSv41kuYFsRdJXyvbwk6f4IASuv8fcpZdeGmXlzvE8EgHcfe9973uDHCI7o6C8ZvwWQ7V0PVB+nmExec973tPNmDEjlIcyWSdM3mKUKBiWNVvGkIF6irdQfmjtYaaLTKknK52tXqSjXdo9fdjvzvYrO+200+BMF2uTseiRqfSUqd9eztvQmQzIt78hb/9ZZM6WQEiyvYtYA7WJtNShHWtv/YLMxQnpAw3yV//h+khDPxyGrXrss0dW+oY+QcbKJa/mplVGfcoef4iZNhUPpVytj4HnyFkMiWeVTd76gR93j30StZc0LRTb9mMkH23OCqEO+hMCrM9ox4MPPjjeCURBPUcRQ3sKtvpY66vVB/Rz2/3o28iUPjRMwvVLFltl9xwZIyr6Qn9yQhbKIi2EwbumLWw/1Fy3npV+nzSzXnnOFj3qR55i/8gEtBm5iI3TV9qz4sO0hzzcz4Ikbe8yGepzrU1aebwDXNWt7clG3squLu6zzZD6antpIN+2rbC9Ere8eiizdLwn+ov+S3ZTGUmAEokFAAP3hz70oRiA7Dk3vJI5i4vByoBkYz8uIAqh7Xln/zuDn4HSRrkGenvESceeOrZdoRwRGs8jVtxNBrA99tgjFCISYKNilhXlscEg5WAwpOAt2mkAlJ4Bj4LyM5DauNYgKhYIDMrilShvSkv55ElJcZX5qQsTP+VuLzxkxEA+PwJkg16DMaLYCFAD5cCViHwZqG2No37qSi7SVtejjz66W2eddcLqpj6sSgZ1C6lyrR111FGxrxwFI+6I/J1noWuktI9hAkSRH3LIIZEX5SeOhyzttycf7o2TTz45lLH87cXHpaX8ZItkUoSeUQ4EQRkpJ/UjbwRUeRyro7aRr/SsaK69mkvRsK1/qQ+CqD7amPyG66Mf2JhZ3kiStChiq9YjK7aJoVCRAa64V73qVZEWIoZI2HeR0kVQ1UfZjzzyyJADYqAvUq42v9Q3xJaIcXJPaxtpaj/vA+ueTYn1dSRG2SndLbfcMtIme+QCqULS9Z0+5KU+CIty63vkou3lJz2kQPm0tUnGsEy0hXIikOTM2qhc2g/RRjoEwdu9nNzsi8h9zT2L/GlPfQCx4apFwPr7Lupb9o8kD3VBrJAOkx5kX5nJl1zVFylhddUetlbiFtb2VrPXR2yCre/bEkobaX/t6pr0pOEeZZCPdwORVG95koN2VvatttrqZgQI2RabJA0fAbz97W8PGdmYW/+esqiCSCQSk4w6iJStt9667LjjjqUSg8HZ/6GSn1KVa6mzulIHpVIHmlIVTFyrg1+pirvU2WscV0VXKpkodTYZ1+pAWS688MK4dsMNN5QnPelJpSqJUpVhqQqp1EGyVOJS6gyw1EG81Jlk5HXWWWfFM5WUlKr8SiUccVzJQVl++eXjf5DvBhtsUCrhGpwpZbvttiuHHXbY4KhEHlVJx//rr79+pAFVoZU6c4x6QZ25lrXWWqvUATuOR2HOnDll2WWXjb/DqMqnPOpRjypVQZSq+Esd2EsdrEMmVcGVH/zgB6Uq9VIV0Vj93Oe4EpY4rqSwVAVVPv/5z8fxJZdcUqpyLZWkxPEwPF+Vcdloo43GjslTW1ZiEOeqQuG/Ku9///vj+pOf/ORy4IEHxjX5KW9VwnH8kpe8JNKryiaOTz311FIVYqnKO9LTRpV4RlpVcZZKfKO8lTSUSgii/SqxKQcddFA8X5VqXK/kJI4vu+yyqE9VuHE8jEqQxtq3lbUqx/i/Etqo5w477FB+/OMfRx+qCj3Kpx6Oq+Iv97rXvULOsMsuu0R/arKoJKFUwlAq+Y3jSnxKJS6RPlQFHfK4/PLL412Q99JLL12qso++ds4558T9Lf1jjz028h8PVUlHfUEeG2+8cdlvv/3i+Oyzzy7bbLNNqWQujisRG2v3PtR72223LZW0hfy9K0cccUT0rTqhiHK6XicBcX8lW1HGfffdN9KuJCLeoTpBiXr98pe/jPuGUclm9EVyhDqRKZWQlUqo4ti7Ly33KJN8KmEpdQJRKpkLGXmnK2GM915+ntH/KvkplXzGO1JJVqmkttRJTqRLrksttVTUH8hJvrvttlsc62f+N84YDyrxi+uVZMV1clxxxRWj/01lZAxQInE7wR5lfkz/Zvd1kIrzZpqsP1UxxXlfT5kJmx2bMTPZs3aAGaDZqFkq94uZphmbGb7ZHwuFWZ/Znlm49ARlm+2b6ZnxsnS0vIGro2/6NtNUnpkzZw7OdJHXG97whvifmZ81g0WClYklqO+uuy1QRumZYbNMcZWwgqmXOrIOzG+GyprRv8czZGj2OxGQO0sIC0Wz5InrEsuj7uTHqmPmXpV5WBKcIwOzfxY3mzw3l1hV2PE/mUtPG7q3jsdRLtdYSljXWAVdZxliVYBWH/eD+nie+3MUzPBZBs3oWRRYF1jnyJMrUX4sGSxCXCr+VzaB/I5ZVvRRlhduGG1vh+0mC1ZCFhhWQVC25o4C5ZSXv67JT/6PfvSjo6+xBCmHdgZ90r39PtkH2TfX2eGHHx5uxebiYqFhFWN9Yln0VR3L1DDkp24sKvqSd2XPPfeMPiVdFiTvYSVW8c6waLJ+kbE6kIe+qI30gxVWWGGQ8k3hPVMXZQKy0+/IFqSzzz77RD/XT5SLbJSHTMmIZZA1TD+Qn2dYi9RZebkI/ciVpRbIuw99Zrx3Uvn0Ny5NVj5WVTFY/T42VZEEKJG4HTA8QEE7x93j828xQEziBmRuFIqGf78Npg0UlMHZINoGrL4CEktA0fjclbJg2qeYkSIYpWj6A59B3D3+NiBaBk3KShwIVxv3AyJkMDbgTgYoXa4OCghGlXU8RdlAAc6aNSuIJFcG4kaxICITgTgS9WkKGigH7ib1By5KMhDbctBBB4VyJEMuQwSUrBqGlcpw+dtx/z7t2foH5SkwnGsJ8VIfXxZtuummcX0Yys8lxYXiqzrP9+syXB5ES37tvGP/k4G+h9w1MgbKhcQ0WQynN4x2vdWz/R31TowCAsHFw+UoaF77tvogIrNnzw5ytv3224frk6tpGPL067eLdwj5U0/vIALCjeUd9M5wScnX9X79bwnIT3/oywipQV7a++vXf39hOD9tQF4tHdfVx3nopw/Dx8PwPJLMNam/+DtZk5hFGUmAEokFAAOYQdhveDBr6J/3f1MAZn9iNSjTdt7gayA2WCJBLcgXDKhmjWazTZm02TmwIhhcER5pSdOAZ3CnOEYNju5r5UFoxPIgUA3yFKuC9JjBinMSU6Hs0m6DZ0tnPBlAv6x9qKeZKGsUAgOtTP1nWp2Rkj5anspDMYqhEmti5i9uxmx7PPTbg/VJfcRbNbhGJsgnhcx6IP3DDjssrHrgGcRTucSqNCi751t5/e83LKP+sf9bndVHwDwrDEsI+YjxGBX8rG2tL6Te4pTaF2j9tIfzdtz/61r7nyzUSdxJHywjrC+gfNCe0T7KMaxQW54t/Xbc2rNfpgbpiFW58MILIz6HdUZ9Wl6CqL0L6ix2isVFjNJ40IYNyIPJgvZjYTHpEAenHH7a2TEC1Mo8P7T72r3eRQHYrFMNyuC6WCV19//wO9H6TENLs8lo+Bik1fqYvyYw/eutbNrFRIMl2ef6e+21V8QkwXCbTTXcvIclEonbDAHKrAKCmM0m+zDDMhhR8A3cLJSIwVCQooHHbF3A6pw5cyJokqsD0VhzzTVjcUEzW/dzO5ntIkBmmGbiyJOBGih6n5azgAiM5KqiIMx+KbNmsRFcKShT2RCclpbAaBYHZbA+kPukQxlSGurDsoS0UYyeE1xKgbQZr/qNB2Z7+bRBX1l8WeMrKe4a+aobyAtpa6Z+oLCUQ+Cx+1l53CdAl4yQNFYSJJArweBOMfbT6IMC1zbKrVzuF0CqHXzZB9wj0mbxki4rlfYmA1YZbSkPZGuTTTYJCww3GgXuPn0CAaVUtaE0kFxQf/m2Y+UhP0G94LyAdM+pj3Ywe5fuKPgayDMsitwcvjyigP3IktJXflC+JmNfHgErlrz81Rf0Ja4/9QRB757RJ4HLRpkRbisfIyvq0/Lzc9z6v3SRAuQF1Ek5pK+8rR83aE/yYJVpX1Lp79qTtZQLUn2QGG3Xt1z2of+TCeUPAoBZgbxjCLMAei4wrmPtLhicZQ/h1G7aWNnHgzpwTbvPewBIMgscsqEO6sYyx/VkMUxy0BfaOwHSUUfXtAO096pZt5xv4wEgPKxZ3iPuPEHSnlcefQE5IiPtJh3XHOu/ZKjtXNN++seURRVuIpGYRAiurTPTCOwV7CyAtRKCuFaJUXn2s58d1wQ+CvjcddddI6hToKj/64AZAbR1hh/nBCvXQSmeh6roIkBTugJapVEHzQg4FqgrT0G1e++99+CJUuoAV44++ugIbBTsePrpp5dKGuJaVQClDr4RECngss4AI1+/ww8/PIJdqxKJ4FbpPu5xj4uA46rkIniyDuZxfvfdd4+AU9cr2YrgzFmzZkV51FW6fSiv+grQFWD6kIc8JOQm6FlQuHQFmDbUwTgCPd37sIc9bCwIGAR7KkNVXqUq2rLeeutF4LU8lJFc1l133ZB7JQyRp2MB0X1UxRByU2b3CfatijrSOOGEE0J2yqjcgpWBHAWpkpfA0koiyzrrrBNB2K4pwwEHHBBl125VGZWnPOUpIUMBzILNlUudjjvuuAiKraS1rLTSStFmgpKVRfry0RaVkIac+/XRhgJ6h0FOAmgf+9jHlvPPP7+89KUvjUBbQc4C2aVbSXAE+AoArso/0tX/qtIfk9vqq69eKvmN/E866aRoJ7IQQC1Yt0HQ9nOf+9xIRz8QtKyOF1xwQfQ79dKG+pt01EN9BdYL9NdvBNZvuOGGka426UNgsrKQcSVfIVv/C4oXhC+ou04SIvhecLT0hqFPV/JaKhmJPqoedRIRgekNldyErLybZCfwXp/XBuQlUNvHAQKQh0FG+o52EaysbY855pi4ppyC6tVXP9XGlWzEb88994z20KYzZ86M+318oAz6pH6s32gTMnzwgx8cMjVGaCPvWQt81s/kv+mmm5ZKhCI4/NBDDy2VKEWe3hd5eVYQdxuH9FvvsfdR+7dxYioit8JIJCYZZldmwKw4Xq/2P3MzmPWxdrgP3NNM0871zc6eHTZtN7B6QDNzt7zGSwucc9+wiR1c86zytTSG7x3v+eHz/lfuVn7Hfv3yOO7Xz//Sacej8vBzvtWzlRPGK5tZrJl+s1A02KKA7HbZZZfBmbno17/lp0wgXz/16OcNw/n7vz0H0oVRMvCM59u54eOWl/+5vVg/fAreBxeX66xSw2j5tLwdK9twXf3f8nO/exy38rS2Adedc62d68N15/sycP946bf7W1qtPKPgGfcP16f932Td3o1heJacBBSzoLrfvf2yNrQyKyPMq3/04T7n3dueaWnA8PsLTSYgbfVzDpxvMmn5tvtb+ZyHlo/jftkbRuUD7bw8PAftvqmIJECJRGLKguKxvhB3gC+D6iw5BnxuIUSCe8rXT4sLKCguUm5NLk1/1YdbSJyPNZ/qzH1wd2I8UHvbbrvtWDxYYnoiCVAikZiyQA7Eq4izEHuCQIh58gWYz59b4O7iAvURn6E+YlvUZ8aMGVEfdbEQXmLeoPIsXuhzb5YPyztYiNRSE4nphSRAiURiykPQsaBsJEjwqyBXAeCLKwSmCmht9Vl++eXjU+rExCAgu+/aETA9nrssMXWRBCiRSCQSicS0w+gIs0QikUgkEokpjCRAiUQikUgkph2SACUSiUQikZh2SAKUSCQSiURi2iEJUCKRSCQSiWmHJECJRCKRSCSmHZIAJRKJRCKRmHZIApRIJBKJRGLaIQlQIpFIJBKJaYckQIlEIpFIJKYdkgAlEolEIpGYdkgClEgkEolEYpqh6/4fkx6TApVRKuIAAAAASUVORK5CYII=\" width=\"576\" height=\"76\"\u003e\u003c/p\u003e\n\u003ch3\u003eC) Particle size:\u003c/h3\u003e\n\u003cp\u003eAqueous dispersion of prepared NS product was scanned in Brookhaven instrument which works on dynamic light scattering principle to get mean size of drug loaded nanosponges.\u003csup\u003e7\u0026ndash;9\u003c/sup\u003e\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eD) Compatibility analysis using FTIR method:\u003c/h2\u003e \u003cp\u003eFTIR spectra of both pure Cefditoren pivoxil and NS forms were produced. The presence of characteristic peak regions that have been noticed in pure drug spectrum were searched in spectrum of nanosponges. This analysis enabled the prediction of drug interactions with other formulative ingredients incorporated to prepare nanosponges. Disc shaped pellet was prepared for each sample by mixing it with KBr and then scanned in FTIR instrument to get spectrum.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e4. Drug compatibility in preformulation study for Floating tablets:\u003c/h3\u003e\n\u003cp\u003eThe compatibility of Cefditoren pivoxil with polymers and other excipients used in tablet formulation blends, was confirmed using Fourier Transform Infrared (FTIR) spectroscopic method as a part of preformulation studies for floating dosage forms. Spectra were generated for two types of physical blends i.e. i) Blend having pure drug, polymers and other excipients ii) Mixture containing NS form of API, polymers and other ingredients. The analysis of generated FTIR spectra for both pure drug and its physical blends was carried out to interpret peak regions of characteristic groups. The status of drug compatibility was known by identifying the presence of any deviations with characteristic API peaks in spectra of physical blends.\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003e5. Preparation of Floating tablets\u003c/h3\u003e\n\u003cp\u003eIn this research, preparation of floating matrix tablets has been done using two separate approaches. In one approach, pure Cefditoren pivoxil was used as an API, whereas in other, pure medicament has been replaced with Nanosponge form of drug. Preparation of tablets was executed using direct compression method. Homogeneous mixing of all the ingredients like pure drug or NS form, MCC, rate controlling polymer and effervescent materials i.e. sodium bicarbonate, citric acid was done in a polybag. Then lubrication of resulted blend was done with magnesium stearate and talc before compression on eight station rotary punching machine using 9 mm flat faced punches (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFormulation composition of Cefditoren pivoxil floating tablets\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFormulative Ingredients (mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eFormulation Code\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eF6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eF7\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eF8\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCefditoren pivoxil (pure)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCefditoren pivoxil\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(as NS forms)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHPMC K100M\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGuar Gum\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMCC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e132.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e132.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e82.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e132.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e82.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCitric acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNaHCO\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMg. Stearate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTalc\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e6) Evaluation of prepared gastroretentive tablets\u003c/b\u003e \u003c/p\u003e\u003cb\u003eA) Characterization for physicochemical properties\u003c/b\u003e: In-vitro methods were applied to perform the evaluation tests like weight variation, hardness, thickness, friability and drug content as per reported methodology in literature.\u003csup\u003e10\u003c/sup\u003e The compliance of obtained results with pharmacopoeial limits was confirmed after their thorough checking and comparison with standards.\u003c/p\u003e\u003cp\u003e \u003cb\u003eB) Floating properties\u003c/b\u003e: Buoyant properties were predicted in 0.1 N HCl (pH 1.2) medium. Estimation of floating lag-time and log-time values was carried out for buoyancy characterization of prepared dosage forms. A beaker (1 litre capacity) containing 900 ml of medium was used for these tests. A dosage unit was placed in medium in which it sinks to bottom instantly and floating lag-time was recorded by noting the time taken by tablet to float on surface of liquid. The duration of buoyancy for this floated tablet after its lag-time was noted as floating log-time.\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eC) In-vitro dissolution study\u003c/b\u003e: Simulated gastric fluid i.e. 900 ml 0.1N HCl (pH 1.2) at 37˚C temperature was opted as medium to estimate the percentage of drug released from floating matrix dosage units. USP type-II (paddle) apparatus was used for this in-vitro testing. The speed of paddle rotation was maintained at 50 rpm. This dissolution test was performed up to 12 hours \u0026amp; the periodic time points to collect 5 ml sample during study were at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12-hour. UV-Visible spectrophotometer was used for scanning of collected samples at λ\u003csub\u003emax\u003c/sub\u003e of 210 nm and absorbances were recorded. API\u0026rsquo;s calibration curve was used to calculate the cumulative % of drug release at each time point with obtained absorbance values.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e \u003cb\u003eD) Drug release kinetics and mechanism\u003c/b\u003e: Fitting the obtained in-vitro drug release data into different equations of zero order, first order and Higuchi, Korsmeyer-Peppas, Hixson-Crowel models \u0026amp; plotting the relevant linear curves, has enabled the confirmation of release-kinetics and release-mechanism of medicament from polymer matrix. The obtained regression values (R\u003csup\u003e2\u003c/sup\u003e) of every straight line were compared to select the best fit linear curve with highest value and that selected respective model was used to explain the drug release kinetics and mechanism.\u003csup\u003e10,11\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eE) FTIR analysis of best formulation for drug compatibility\u003c/b\u003e: FTIR analytical method was opted to check the possibility of drug interaction with other excipients in selected best formulation. The dosage unit was converted to powder by grinding it in a mortar. The ground tablet powder was mixed with KBr to prepare it as disc shaped pellet and scanned in spectrophotometer to get spectrum. The characteristic peaks of pure drug (as found in API spectrum) were verified in resulted spectrum for their presence and deviations to confirm the status of compatibility.\u003csup\u003e10\u0026ndash;12\u003c/sup\u003e\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e1. Drug compatibility in NS preformulation study:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 1: FTIR spectra of i) Pure Cefditoren pivoxil and ii) NS formulation blend\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Characterization of Drug loaded Nanosponges\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) Practical yield, Drug entrapment efficiency and Particle size of Nanosponges:\u0026nbsp;\u003c/strong\u003eThe final weight of yielded nanosponges has indicated 6.76 % of practical wastage. After experimentation, the obtained experimental yield of NS formulation was found to be 93.24 % w/w. The resulted nanosponges have found to be well entrapped with drug and entrapment efficiency value was 93.66% w/w.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) FTIR spectroscopic analysis of NS:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 3: FTIR spectra of pure Cefditoren pivoxil and Nanosponge formulation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Drug compatibility in floating formulation blends:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 4: FTIR spectra of i) Pure Cefditoren pivoxil and ii) Blend with pure drug iii) Blend with nanosponges\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. Evaluation of floating tablets\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) Physicochemical characterization:\u0026nbsp;\u003c/strong\u003eThe noticed results for weight, thickness, friability and drug content of all formulations were converted to get mean \u0026plusmn; SD values through minor calculation. All these results are represented in below Table 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Results for physicochemical characterization of floating formulations\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFormulation Code\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight (mg)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e749\u0026plusmn;0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e747\u0026plusmn;1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e751\u0026plusmn;1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e750\u0026plusmn;\u0026nbsp;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e749\u0026plusmn;\u0026nbsp;1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e752\u0026plusmn;\u0026nbsp;0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e748\u0026plusmn;\u0026nbsp;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e749\u0026plusmn;\u0026nbsp;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eThickness (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.6\u0026plusmn;0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.5\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.5\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.4\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.5\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.4\u0026plusmn;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.6\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e4.5\u0026plusmn;0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFriability (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.88\u0026plusmn;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.74\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.63\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.81\u0026plusmn;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.54\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.69\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.59\u0026plusmn;0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.79\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrug content (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e98.9\u0026plusmn;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e99.6\u0026plusmn;1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e99.2\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e98.8\u0026plusmn;0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e99.3\u0026plusmn;1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e98.7\u0026plusmn;1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e99.7\u0026plusmn;1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e99.4\u0026plusmn;1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eB) Floating lag-time and log-time:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Buoyant properties of floating formulations\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFormulation Code\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFloating lag time (min)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e11.2\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e9.6\u0026plusmn;0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e8.6\u0026plusmn;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e6.4\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e5.6\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.6\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;0.24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.1\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;0.22\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.9\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;0.54\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFloating duration (hrs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e7.7\u0026plusmn;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e8.9\u0026plusmn;0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e9.1\u0026plusmn;1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e10.4\u0026plusmn;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e11.1\u0026plusmn;0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eC) In-vitro drug release:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Dissolution study data for floating tablets\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime (hrs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 594px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCumulative % of Cefditoren pivoxil Release*\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.91\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.89\u0026plusmn;0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e0.87\u0026plusmn;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.74\u0026plusmn;0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.24\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.06\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.97\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;0.21\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.86\u0026plusmn;0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e2.89\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2.45\u0026plusmn;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e2.32\u0026plusmn;0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.98\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e4.36\u0026plusmn;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e3.97\u0026plusmn;0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.82\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;0.19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2.16\u0026plusmn;0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e3.44\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e3.15\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e3.21\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2.96\u0026plusmn;0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e8.76\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e7.11\u0026plusmn;0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7.11\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.02\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e6.49\u0026plusmn;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e6.63\u0026plusmn;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e5.97\u0026plusmn;0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e5.44\u0026plusmn;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e5.09\u0026plusmn;1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e15.84\u0026plusmn;1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e13.29\u0026plusmn;1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12.36\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.09\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e11.29\u0026plusmn;1.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e8.29\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e8.03\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e8.12\u0026plusmn;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e7.49\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e33.73\u0026plusmn;1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e28.66\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e27.66\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.29\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e23.89\u0026plusmn;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e15.45\u0026plusmn;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e14.29\u0026plusmn;1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e13.97\u0026plusmn;1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e11.68\u0026plusmn;1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e44.76\u0026plusmn;1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e36.99\u0026plusmn;1.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e33.63\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.67\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e31.19\u0026plusmn;1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e35.24\u0026plusmn;1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e32.22\u0026plusmn;1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e31.43\u0026plusmn;1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e29.87\u0026plusmn;1.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e62.19\u0026plusmn;1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e55.12\u0026plusmn;1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e57.19\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.37\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e53.66\u0026plusmn;1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e49.77\u0026plusmn;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e46.47\u0026plusmn;1.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e44.53\u0026plusmn;0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e38.87\u0026plusmn;1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e76.39\u0026plusmn;1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e67.41\u0026plusmn;1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e72.19\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.88\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e69.34\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e69.89\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e63.88\u0026plusmn;1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003e59.75\u0026plusmn;1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e46.39\u0026plusmn;1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e88.12\u0026plusmn;1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e76.27\u0026plusmn;1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e99.77\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;1.13\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e91.74\u0026plusmn;1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*The representation of all values was done as \u003cstrong\u003eMean\u0026nbsp;\u003c/strong\u003e\u0026plusmn; SD; n=3\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD) Kinetics and mechanism of API release from floating dosage forms:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: R\u003csup\u003e2\u003c/sup\u003e values for drug release kinetics and mechanism models\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"593\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFormulation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eZero order\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFirst order\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHiguchi\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKorsmeyer-Peppas\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHixson-Crowell\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9815\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.9669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.9254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9863\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.3975\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e0.9765\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9811\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.9727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.9272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n 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\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0.9292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9834\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9755\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.9561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.3878\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e0.9704\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9877\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.7861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9786\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.9728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e0.9287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.9844\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.9552\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.9772\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.971\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.5414\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.989\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eE) Drug compatibility in F7 formulation:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eFig. 7: FTIR spectra of pure Cefditoren pivoxil and F7 formulation\u003c/strong\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003e1. Drug compatibility in NS preformulation study:\u0026nbsp;\u003c/strong\u003eAll the characteristic peak regions identified in pure Cefditoren pivoxil at 3304.17, 3074.63, 3061.13, 3724.67 cm\u003csup\u003e-1\u003c/sup\u003e (\u0026gt;N-H\u003csub\u003e\u0026nbsp;\u003c/sub\u003estretching), 1629.90, 1606.76 and 1591.33 cm\u003csup\u003e-1\u003c/sup\u003e (\u0026gt;C=N stretching), 1348.29, 1334.78, 1303.72, 1284.63, 1253.77 cm\u003csup\u003e-1\u003c/sup\u003e (\u0026gt;C-N stretching) were noticed in spectrum of NS formulation blend (Fig. 1). These API peaks were unaltered in blend witnessing the absence of medicament interaction with other additives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Characterization of Drug loaded Nanosponges\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) Practical yield, Drug entrapment efficiency and Particle size of Nanosponges:\u0026nbsp;\u003c/strong\u003eA good API loading in sponge-like matrix of polymer present in formulation, has been witnessed by this result. The mean size of prepared nanosponges was less than 1 \u0026micro;m. In size and surface analysis, it was noted that resulted nanosponges were individual, spherical with smooth surface (Fig. 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) FTIR spectroscopic analysis of NS:\u0026nbsp;\u003c/strong\u003eThe drug characteristic peaks seen in spectrum of nanosponge formulation were at same wavenumber regions as those present in spectral graph of pure Cefditoren pivoxil. This observation witnessed the drug compatibility with other incorporated ingredients in NS forms (Fig. 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Drug compatibility in floating formulation blends:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the characteristic peaks seen in drug spectrum have been found in spectra of both physical blends and also the peak wavenumber-regions were almost seen unchanged. This analytical result has indicated the existence of no interactions among the drug and all other formulative additives used in development of floating tablets (Fig. 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. Evaluation of floating tablets\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA) Physicochemical characterization:\u0026nbsp;\u003c/strong\u003eA good compliance with pharmacopoeial standards has been observed in all the noticed results. Hardness values of all developed dosage forms were found to be in\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB) Floating lag-time and log-time:\u0026nbsp;\u003c/strong\u003eEnriched floating properties have been seen with NS based formulations (F5-F8) compared to dosage units containing Pure Cefditoren pivoxil (F1-F4). Floating lag-time and log-time were found to be more and less, respectively in conventional formulations having pure drug when compared the same parameters in tablets embedded with NS form of drug (Table 3). Enriched porous matrix formation that caused to more entrapment of CO\u003csub\u003e2\u003c/sub\u003e in formulations F5-F8 might be the reason for their improved buoyancy. A fact has been evident from all the observed results that an enriched buoyancy (less lag-time) could be seen with tablets incorporated with 1:1.25 ratios of drug and polymer in comparison to 1:1 dosage forms. A quick formation of hydrodynamically balanced layer around the tablets due to swelling of polymer in these formulations, might be a reason for this positive result.\u003csup\u003e8\u003c/sup\u003e The tablets having 1:1.25 ratio composition of drug and polymer, have also exhibited more floating duration. The retention of CO\u003csub\u003e2\u003c/sub\u003e for longer time in compact porous polymer matrix formed inside the dosage form after swelling may be the another responsible factor for this enhanced buoyancy duration in F2, F4, F6 and F8 formulations.\u003csup\u003e8,10\u003c/sup\u003e A longer buoyancy (\u0026gt;12 hrs) has been noticed with F6, F7 and F8 formulations irrespective of their polymer nature and its proportion. Enriched cross linking of polymer chains with NS matrix components, might have enabled the formulations to possess these better floating properties.\u003csup\u003e9,10\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC) In-vitro drug release:\u0026nbsp;\u003c/strong\u003eThe percentage of dissolved drug at the end of 12 hrs was noted and compared for all the formulations (Fig. 5). More and comparatively fast drug release has been noticed with the tablets having less amount of polymer (1:1 ratio of drug and polymer). The ability of controlling the drug release from dosage units was found to be more with Guar gum (F3, F4) when compared to HPMC K100M (F1, F2) in formulations designed with pure form of drug. The ability of this natural hydrophilic polymer (Guar gum) to swell more and form porous matrix network might have led to delayed release of drug.\u003csup\u003e10-12\u003c/sup\u003e But, a greater ability of Guar gum to dissolve and fasten the drug release from tablets (F7, F8) was noticed in comparison to HPMC K100M (F5, F6) in formulations loaded with NS form of drug (Table 4). The more compatibility of Guar gum polymeric chains with sponge-like structures that led to enriched permeation of dissolution medium into tablet interior might be a cause for increased dissolution of drug in both F7 and F8 formulations.\u003csup\u003e11,12\u003c/sup\u003e Moreover, enriched drug dissolution and release have been noticed from both polymers (HPMC K100M and Guar gum) when they were combined with nanosponge matrices (F5-F8). But, the same polymers have allowed the less dissolution and decreased release of pure API form in F1 to F4 formulations. As per the literature, this less drug dissolution and increased controlled manner of release may be due to more interlocking of free polymeric chains (without sponge networks) which avoided the permeation of liquid medium inside the tablet.\u003csup\u003e7,8\u003c/sup\u003e More dissolution percentage and best controlled release pattern has been noticed from F7 containing Cefditoren pivoxil in NS form, 1:1.25 ratios of drug and Guar gum (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD) Kinetics and mechanism of API release from floating dosage forms:\u0026nbsp;\u003c/strong\u003eZero order kinetics have been seen with the drug release from tablets with pure Cefditoren pivoxil (F1-F3), but F4 formulation has released the medicament through first order kinetic pattern. It was found to be following first-order (F5, F6) and zero-order (F7, F8) patterns in NS loaded formulations (Table 5). The mechanism of drug release from F1-F4 formulations was \u0026lsquo;Super case-II transport\u0026rsquo; mode (Korsmeyer-Peppas model) where the diffusion of medicament has been controlled by swelling of polymer matrix. F5 and F8 formulations have released the drug through surface erosion mechanism (Hixson-Crowell model). The possible reasons for this mechanism may be i) less swelling \u0026amp; improper interlocking of polymeric chains with NS sponge-like structures by HPMC K100M at less proportion in F5 and ii) huge expansion of polymeric (Guar gum at high proportion) matrix due to more permeation of medium into a tablet.\u003csup\u003e10,11\u003c/sup\u003e A concentration gradient dependent Fickian diffusion mechanism (Higuchi model) was observed with NS-based F6 and F7 formulations. A systematic arrangement of both sponge and polymeric matrices as an array, made the drug to be diffused out in more controlled way from F6 and F7 tablets.\u003csup\u003e7,8\u003c/sup\u003e More predictable and controlled diffusion (Zero order and Higuchi model) was found in F7 tablets dissolution. As the cumulative drug release was also found to be more than 99% at the end of 12 hours, F7 was selected as best formulation. A representation of F7 graphs related to \u0026lsquo;kinetic and mechanism models\u0026rsquo; is evident in Fig. 6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eE) Drug compatibility in F7 formulation:\u0026nbsp;\u003c/strong\u003eCharacteristic peak regions appeared in FTIR spectrum of pure Cefditoren pivoxil were noted and compared with the peaks seen in F7-spectrum (Fig. 7). A good compliance has been noticed between \u0026lsquo;all noticed regions of peaks in pure drug\u0026rsquo; and \u0026lsquo;wave numbers of all characteristic stretchings in best formulation\u0026rsquo;. So, the presence of drug compatibility with other used excipients in selected best dosage forms has been witnessed with observed facts in spectra.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eLoading of poorly soluble drug in to nanosponges could greatly enhance its solubility and also matrix forming polymeric chains were found to be compatible with NS forms. More drug dissolution has been noticed with tablets prepared with NS units. Sponge-like porous matrix with more entrapped CO\u003csub\u003e2\u003c/sub\u003e in nanosponge units has led to increased buoyancy in NS loaded floating tablets (F5-F8). Good floating and drug release have been resulted from both the polymers (HPMC K100M and Guar gum) in combination with NS forms. A combination of NS form of drug and Guar gum in 1:1 ratio in F7 has shown best buoyancy and more controlled drug release among all 8 tablet compositions. It can be concluded that the conversion of poorly soluble drug to NS form and incorporation of modified API in floating formulation can result in to a successful gastroretentive dosage unit with more promising buoyancy and drug release.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNanosponges\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGIT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGastrointestinal Tract\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGastroretentive\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBCS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBiopharmaceutical Classification System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFTIR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFourier Transform Infrared\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eActive Pharmaceutical Ingredient\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEthyl cellulose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePVA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolyvinyl alcohol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emg\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emilligrams\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eml\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emillilitre\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003erpm\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erotations per minute\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e˚C\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDegree Celsius\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003enm\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enanometres\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPMC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHydroxy Propyl Methyl Cellulose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMicro Crystalline Cellulose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emm\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emillimetre\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\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\u003eThere was no conflict of interest declared by authors.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNot Applicable\u003c/p\u003e \u003cp\u003e1. \u003cb\u003eEthics Statements\u003c/b\u003e: Not Applicable.\u003c/p\u003e \u003cp\u003e2. \u003cb\u003eHuman Ethics \u0026amp; Consent to participate\u003c/b\u003e: Not Applicable.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e1. Naga Raju Kandukoori: Involved in designing of research protocol and wrote the main content 2. Gundegani Saikumar: Prepared tables for all the results3. Deepika B: Involved in preparation of figures and analysis of FTIR4. Katla Venu Madhav: Checked the plagiarism of manuscripts and done required corrections\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe, all the authors, are grateful to the management of St. Pauls College of Pharmacy for arranging the lab facilities and timely encouragement throughout the study. We are thankful to Vista Labs, Hyderabad for gifting us the API sample.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003e1. The discussions made for results of floating lag time and log time are supported by the below mentioned reference sourcesa) doi: 10.1080/10717544.2023.2174208b) doi: 10.1016/j.carbpol.2018.05.011c) doi: 10.5958/0974-360X.2018.00720.52. The discussions made for results of dissolution study and drug release mechanism, kinetics are supported by the below mentioned reference sourcesa) doi: 10.5958/0974-360X.2018.00720.5b) doi: 10.1155/2023/4322375c) doi: 10.4274/tjps.59454\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGloria MC, Juan DR, Achmad H, Monica MJ, Isidoro C (2024) Current trends in 3D printed gastroretentive floating drug delivery systems: A comprehensive review. International Journal of Pharmaceutics 663: 124543: 1-20. \u003c/li\u003e\n\u003cli\u003eNaga L, Ganga B, Krishna P, Swathi K, Naga R, Chinna E (2013) Floating Drug Delivery Approaches for Prolonged Gastric Retention. Research J. Pharm. and Tech 6(7): 706-710. \u003c/li\u003e\n\u003cli\u003eAkash G, Wen-Cheng L, Himansu C, Rutvi A, Talever S, Ramkumar C, Braj ND (2024) Nanosponge: A promising and intriguing strategy in medical and pharmaceutical science. Heliyon 10: e23303: 1-19. \u003c/li\u003e\n\u003cli\u003eSunil K, Babu LJ, Rekha R (2022) A new perspective of psoriasis: Dithranol nanosponge loaded hydrogels. Applied Surface Science Advances 12: 100347: 1-9. \u003c/li\u003e\n\u003cli\u003eOlivia S, Sreejan M, Gouranga N, Subrata J, Sougata J (2023) Recent advances in alginate based gastroretentive technologies for drug delivery applications. Medicine in Novel Technology and Devices 18: 100236: 1-12.\u003c/li\u003e\n\u003cli\u003eMohammed J, Mohd Sajjad AK, Mohammed S, Saira Z, Hanan Mohammed HS, Layali IA, Heba RA (2023) Development of apigenin loaded gastroretentive microsponge for the targeting of Helecobacter pylori. Saudi Pharmaceutical Journal 31: 659-668. \u003c/li\u003e\n\u003cli\u003eAshish YP, Khanderao RJ, Sharayu PR, Ashwini SS, Milind JU. Formulation and Evaluation of Nanosponges Loaded Hydrogel of Metformin Hydrochloride. Indian Journal of Pharmaceutical Education and Research. 2023; 57(1): 53-61. \u003c/li\u003e\n\u003cli\u003eDalia AG, Mahasen AR, Danah AA, Jenan AA, Rafa SA, Reema MA, Sara AA, Siham AA (2023) Formulation and evaluation of Piroxicam nanosponge for improved internal solubility and analgesic activity. Drug Delivery 30(1): 1-10. \u003c/li\u003e\n\u003cli\u003eCassiana M, Gabriela CM, Clarissa GB, Jamil A, Marcos AS, Gilles P (2018) Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity. Carbohydrate Polymers 195: 586-592.\u003c/li\u003e\n\u003cli\u003eNaga Raju K, Fasiha M, Ravali K, Syeda WJ, Deepika B, Narsimha Reddy Y (2018) Studies on Influence of Polypropylene Foam Powder on Gastroretentive properties of Floating tablets of Cefditoren Pivoxil. Research J. Pharm. and Tech 11(9): 3923-3926. \u003c/li\u003e\n\u003cli\u003eAdane Y, Chernet T, Zewdu Y, Solomon A (2023) Formulation and In-vitro Evaluation of Furosemide Floating Matrix Tablets using Boswellia Papyrifera resin as Matrix forming Polymer. BioMed Research International 1-11.\u003c/li\u003e\n\u003cli\u003eLatha K, Kishore C, Naseeb BS, Shailaja T (2018) Formulation and Evaluation of Sintered Floating Tablets of Cefpodoxime Proxetil. Turk J Pharm Sci. 15(3): 278-290. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"beni-suef-university-journal-of-basic-and-applied-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jbas","sideBox":"Learn more about [Beni-Suef University Journal of Basic and Applied Sciences](https://bjbas.springeropen.com)","snPcode":"43088","submissionUrl":"https://submission.springernature.com/new-submission/43088/3","title":"Beni-Suef University Journal of Basic and Applied Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Buoyancy, Floating, Gastroretentive, Cefditoren pivoxil, Nanosponges, Guar gum","lastPublishedDoi":"10.21203/rs.3.rs-6419189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6419189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe main objective of this research was to develop a novel gastroretentive formulation for Cefditoren pivoxil, an insoluble and poorly permeable drug. Floating and drug release characteristics of tablets formulated with pure Cefditoren pivoxil were compared with the same of formulations loaded with nanosponges (NS) form of drug.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTest results related to physicochemical properties of all prepared tablets were observed to be in compliance with standards. More floating lag time and less log time have been resulted from the formulations with pure form of drug (F1 to F4), whereas, vice-versa was found with NS based dosage forms (F5 to F8). An evaluation test for in-vitro drug release was performed for all the dosage units and more controlled release pattern with diffusion mechanism was seen from tablets loaded with NS. F7 with a combination of NS form of drug and Guar gum in 1:1 ratio has shown best buoyancy and more controlled drug release among all 8 tablet compositions.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe importance and need for entrapment of an insoluble, less permeable drug to obtain the fruitful buoyant and drug release properties from Gastroretentive tablet dosage forms has been witnessed by all the observed results.\u003c/p\u003e","manuscriptTitle":"Formulation and Evaluation of Buoyant tablets loaded with Nanosponges containing entrapped Cefditoren pivoxil","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 11:18:18","doi":"10.21203/rs.3.rs-6419189/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-07T11:48:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-27T15:03:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T13:31:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2438260618984737644150483753533459842","date":"2026-01-06T07:38:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303088499020859168255137328891531872971","date":"2026-01-05T10:40:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-29T06:39:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164646909996373575328493594099415604826","date":"2025-09-24T11:51:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-13T09:23:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-24T12:43:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-24T12:40:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Beni-Suef University Journal of Basic and Applied Sciences","date":"2025-04-10T10:17:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"beni-suef-university-journal-of-basic-and-applied-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jbas","sideBox":"Learn more about [Beni-Suef University Journal of Basic and Applied Sciences](https://bjbas.springeropen.com)","snPcode":"43088","submissionUrl":"https://submission.springernature.com/new-submission/43088/3","title":"Beni-Suef University Journal of Basic and Applied Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b88619f0-427a-482e-8ded-dc761dee4942","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T14:57:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 11:18:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6419189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6419189","identity":"rs-6419189","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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