Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market

Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market | 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 Short Report Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market Samiah Alhabardi¹, Gamal Mahrous¹, Asma Alshahrani¹, Ehab Taha This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4672508/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The fundamental objective in developing any drug delivery approach is to achieve effective and safe therapy. Medications classified as generics are those that contain the same active ingredients and have the same quality as the reference medications. Several generic drugs are available on the market, all at a reasonable cost. In this study, the quality of Three generic brands of diclofenac dispersible tablets (DT) available in the Saudi market was assessed, namely: G1 and G2, and G3. Except for the borderline performance of one generic formulation (G3), all formulations passed in vitro quality tests according to the United States Pharmacopoeia. According to the US Pharmacopoeia, every generic formulation passed in vitro quality tests, except for one generic formulation (G3) that performed inconclusively. All brands demonstrated minimal weight variation, with average weights falling within the acceptable range of ±5% from the mean and a rapid dispersion time of around 5 sec. All the brands displayed acceptable friability and minimal weight loss. The potency results demonstrated that all of the three brands complied with United States Pharmacopeia (USP) specifications, which typically fall between 90% and 110% of the labeled amount. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with additional samples. G1 and G2 tablets passed the USP Acceptance criteria in stage one, and G3 tablets met the requirements in stage two. G1 showed the highest DE (%78.83), followed by G2 (%72.23), and G3 (%67.50). The G1 dissolution data, which showed the highest dissolution efficiency, were used as the reference product to calculate the similarity factor (f2 (ratio. G1 (Reference) and G2 with an f2 of (58.3) have similar dissolution profiles. G3, with an f2 of (47.5) showed borderline performance. This study highlights the importance of post-marketing evaluations of generic drugperformance. diclofenac generic brands dispersible tablets Saudi market and quality control. Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Generics are medications that contain the same active ingredients and have the same effects as reference brand medications. There are several brands of generic medications on the market, all at reasonable costs, which reduce budgetary impact and facilitate the cost-effective use of available resources [1]. Moreover, in recent years, the Saudi government has been pushing for generic medication by distributing it at no cost to government hospitals. Manufacturers receive numerous benefits in exchange for producing less expensive medications. Therefore, the use of generic medications has increased globally in recent years [2]. In 2012, the global sales of generic drug products were valued at 67 billion USD and are predicted to increase to 99 billion USD by 2026. This represents a 32 billion USD increase in sales over the previous 14 years [3]. Similar to branded medications, generic medications must receive Saudi Food and Drug Authority (SFDA) approval to ensure their effectiveness. According to the SFDA, generic medications must meet the same high standards for purity, potency, and stability as branded medications. Bioequivalence testing was performed according to the manufacturer’s instructions [4]. Even though bioequivalence testing is required before generic drugs can be sold in Saudi Arabia, continuous evaluation is necessary to guarantee that the intended quality is upheld after marketing. Several generics in Saudi Arabia have passed the bioequivalence testing [5]. Diclofenac is one of the most widely used generic drugs in the Saudi Arabian market. Diclofenac is a non-steroidal anti-inflammatory medication (NSAIDs) used for the treatment and management of acute and chronic pain associated with inflammatory conditions, especially those involving the musculoskeletal system. Diclofenac is available in various tablet forms to suit the needs of different patients. These forms include modified-release, enteric-coated, and film-coated tablets; sustained-release tablets; and dispersible tablets. Diclofenac side effects include gastrointestinal (GI) irritation, wind or loss of appetite, mild rash, and severe stomach pain [6]. Severe stomach pain is the most undesirable side effect observed in these patients. Thus, dispersible tablet formulations can overcome GI problems; in such cases, administration of the dispersion prevents localization of the drug in the stomach. Dispersible tablets (DTs) are defined in the European Pharmacopeia as «uncoated or film-coated tablets intended to be dispersed in water before administration to produce a homogeneous dispersion» [7]. DTs are typically dispersed within 3 min in approximately 5 to 15 mL of water at 15 to 25°C [7]. Dispersible Tablets have several advantages such as ease of manufacturing and transportation, good physical and chemical stability, precise dosage and ease of administration which make them a great substitute for elderly and pediatric patients who struggle with swallowing [8]. In addition, they undergo rapid disintegration and absorption of medicines, which provides a rapid onset of action. DTs differ from oral disintegrating tablets (ODTs) because they are tablets are designed to create a homogenous dispersion by dispersing in water before to administration. In contrast, ODTs are tablets that are placed in the mouth, where they break down quickly before being swallowed. DT therefore combines the advantages of a conventional tablet formulation (stability) with the ease of administration offered by a liquid formulation [9]. Our initial market research identified dispersible tablets (DTs) as potential areas for investigation. However, upon closer examination, we were surprised to find the need for the current study to specifically focus on dispersible tablets containing diclofenac in the Saudi market. This gap in knowledge provides valuable opportunities. This study has aimed to assess the quality of three generic diclofenac dispersible tablets (DT) available in the Saudi market. To achieve this objective, quality control studies were conducted based on the pharmacopeial criteria. 2. Materials and methods 2.1. Chemicals and reagents Diclofenac sodium salt (DS) was purchased from Sigma-Aldrich (SIGMA, MO). Various local marketed generic diclofenac products (G1, G2, and G3), each containing 46.5 mg diclofenac acid equivalent to 50 mg diclofenac sodium salt were used as seen in Table 1 . All other chemicals and solvents were high-quality reagent grade. Table 1 Diclofenac marked products in Saudi Arabia Product Manufacturer Strength Batch number/lot number Manufacturing date Expiry Date G1 SPIMACO 50 mg 1144317 MAY 2023 MAY 2025 G2 GLOBAL PHARMA 50 mg DT B254 APRIL 2022 APRIL 2025 G3 JAMJOOM PHARMACEUTICALS COMPANY 50 mg ZN0184 DECEMBER 2022 DECEMBER 2025 3. Methods 3.1. Calibration curve Two assays were performed using UV spectrophotometry and HPLC. 3.1.1. UV Spectrophotometric assay A Calibration curve was constructed in phosphate buffer (pH 6.8), and 50 mg of DS was accurately weighed using an analytical balance (Model no. B203-S, Mettler Toledo, Switzerland). DS powder was dissolved in 50 ml methanol (1000 µg/ml) to form a stock solution. Different concentrations: (3,6,9,12,15, and 18 µg/ml) were made using phosphate buffer at pH 6.8 and measured at 276 nm wavelength against a blank using UV spectroscopy. Their absorbance was plotted against corresponding concentration to construct a calibration curve. 3.1.2. High-performance liquid chromatography (HPLC) assay The method described in USP 41 was followed with some modifications. The mobile phase was consisting of an isocratic mixture of acetonitrile and 0.1 M ammonium acetate solution in a ratio of 1:1 (v/v). The mobile phase was prepared fresh each day for analysis, filtered through a 0.45 µm Millipore filter and degassed by sonication before experimenting. For the analysis of DS samples, 50 µl of each sample was injected into HPLC Waters system consisting of an Autosampler (model no. 717) (plus), pump model (no. 1525), and Dual λ Absorbance UV detector model (no. 2487) that adjusted at 276 nm. DS separation was performed using (Nova-Pak®) column (C18, 4 µm, 3.9 × 250 mm). The column temperature was kept at 29°C during the analysis, and the flow rate was adjusted at 1 ml/min [10]. The calibration curve was constructed by accurately weighing 50 mg of DS using an analytical balance (Model (No. B203-S, Mettler Toledo, Switzerland) and dissolved in 50 ml methanol (1000 µg/ml). Serial dilutions were prepared in different concentrations (15.6, 31, 62.5, 125, 250, and 500 µg/ml) and were measured using HPLC using the above-mentioned method. 3.2. Quality control tests 3.2.1. Physicochemical characteristics 3.2.1.1. Hardness, Thickness and Diameter A hardness tester (EH01P, Electrolab, India) was used in order to assess the strength of each tablet. A single tablet was positioned between the jaws of the device, and the force was gradually increased until the tablet broke. The breaking point indicated the breaking strength of the tablet. Hardness tests were conducted using 10 tablets of each brand. The thickness and diameter were measured using a micrometer (M&W, Sheffield, England) on twenty tablets from each of the three brands studied. The average value of each dimension was recorded. 3.2.1.2. Dispersibility Dispersibility is a physical process related to the mechanical breakdown of a tablet or granulated particles into smaller particles, representing the breakage of interparticle interactions generated during tablet compaction of granulated particles of the active pharmaceutical ingredient (API) and excipients. Generally, after a liquid wets the tablet surface and penetrates the pores, it breaks down into smaller particles and disintegrates. Dispersibility is a physical process involving the mechanical breakdown of interparticle interactions created during compression of the tablet which result in smaller particles and disintegrates. This process occurs when liquid wets the tablet surface and enters the pores inside tablets. The criteria of dispersible tablets are to disintegrate within 3 min by using water at 15–25°C. To test the dispersibility, one tablet was placed in 25 ml of water and stirred until it was completely dispersed. The test was repeated using six tablets of each brand [7]. 3.2.2. Friability The stability of tablets is determined according to USP41-NF36. Briefly, 20 tablets were weighed (W1) and place them in the friability instrument (Erweka, TA3R, Heusenstamm, Germany) and they rotated at 25 rpm for 4 minutes. Then, the tablets were weighed again after removing the residue (W2) and the friability was calculated as follows: % Friability = 100× (W1 − W2)/W1 (Eq. 1) For tablet unit weight equal to or less than 650 mg, take a sample of whole tablets as near as possible to 6.5 g [10]. 3.2.3. Weight variation A weight-variation test was performed to ensure uniformity in the weight of the prepared tablets. Twenty tablets from each formulation batch were randomly selected and accurately weighed one by one using a digital scale, and their average weights were calculated and recorded as mean ± SD. 3.2.4. Content uniformity Content uniformity was determined by taking a sample of not less than (NLT) 30 tablets. Ten units were individually assayed as directed in the individual monograph assay. The requirements are met USP41-NF36 if the acceptance value of the first 10 dosage units is less than or equal to L1% (i.e. ≥15). If the acceptance value was greater than L1(%, i.e., > 15), the next 20 units were tested. The requirements are met if the final acceptance value of the 30 dosage units is less than or equal to L1%(i.e. ≥15) and all individual dosage units fall within the range [1+(0.01) (L2)]M to [1(0.01) (L2)] M. I. no dosage unit result can be less than [1-(0.01) (L2)] M while on the high side no dosage unit result can be greater than [1+(0.01) (L2)]. SP41-NF36 (10). The acceptance value (AV) was calculated using the following formula: AV = (M-X-) + ks ( Eq. 2) Where, k = acceptability constant. n = sample size (no. of units): if n = 10 then k = 2.4 if n = 30 then k = 2.0 s = sample standard deviation. M= Reference Table 2: Acceptability value conditions for content uniformity Conditions Value if 98.5% ≤ X- ≤ 101.5 % M = X-, (AV = Ks) If X- 101.5% M = 101.5%, (AV=X– -101.5+Ks) 3.2.5. Chemical potency We evaluated the chemical potency by taking a sample of 10 tablets from each brand, grinding them together, and then measuring a portion equivalent to the average tablet weight. For a product to be considered acceptable, its weight should be within 90% to 110% of the amount stated on the label [10]. 3.2.6. In vitro dissolution Dissolution test is one of the standard requirements for the tablets to evaluate the drug release. The dissolution test was performed according to USP 41-NF 36 using (apparatus 2 (DT-70 dissolution test instrument, manufactured by (Pharma Test, Germany). The paddle was driven at 50 rpm in 900 ml of phosphate buffer (pH 6.75–6.85). Medium samples were withdrawn at 5, 10, 15, 20, 30, and 45 min. The amount of diclofenac dissolved in the dissolution medium was determined using spectrophotometry at a wavelength of 276 nm. Phosphate buffer (pH 6.8) was prepared by mixing sodium dihydrogen phosphate (ROMIL UK) 34 g, and sodium hydroxide (Loba Chemie India) 4.5 g in a volumetric flask containing 5 L distilled water. The dissolution efficiency (DE) was calculated according to the following formula: 4. Results 4.1. Physicochemical characteristics Color: A white color. Odor: Clean and neutral, with no detectable odor. Shape: Square for G1, round for G3 and G2. Table 4 summarizes the main result. Table 4 In-vitro quality tests of three generic dispersible tablets containing diclofenac available on the Saudi market. Hardness (Kp) mean (± SD%) n = 10 Thickness (mm) mean (± SD%) n = 10 Diameter (mm) mean (± SD%) n = 10 Dispersion Test (sec) mean (± SD%) n = 6 Friability % loss n = 20 or 60 Weight variation (mg) mean (± SD%) n = 20 Potency Average content %)) mean (± SD%) n = 10 G1 6.07 (0.3) 4.50(0.006) 10.1(0.01) 5(0.63) 0.62% 304٫10(4.54) 106٫5%(2.17) G2 6.015(0.2) 3.53(0.005) 8.02(0.05) 5 (0.63) 0.94% 198٫91(1.190) 105٫4%(4.4) G3 5.87(0.4) 4.53(0.006) 9.50(0.08) 5.16(0.75) 0.64% 301٫13(1.048) 104٫2%(4.8) 4.1.1. Hardness, thickness, and diameter The hardness values of all three generic brands (G1, G2, and G3) met the established acceptance criteria (4–8 kp) for uncoated tablets. The individual crushing strengths measurements were 6.07(0.3), 6.015(0.2) and 5.87(0.4), for G1, G2, and G3 respectively. Statistical evaluation of the diameter was performed to determine the diameter consistency of G1, G2, and G3. The analysis revealed minimal variation, with average values of 10.1(0.01), 8.02(0.05) and 9.50(0.08), respectively. This uniformity ensures that all of the brands comply with the stringent quality control standards. The thickness should be controlled within ± 5% variation of standard value, and the results showed G1 4.50(0.006), G2 3.53(0.005), and G3 4.53(0.006) fell within the acceptable range of ± 5% variation from the average value as shown in Table 4 . 4.2 Calibration curves 4.2.1. UV Spectrophotometric assay The absorbance was linear over the concentration range (21–3 µg/ml) R-squared as seen in Figure (1). We also determined the coefficient of determination (R2 = 0.999). The drug concentration was calculated using the following equation: A = 0.0356C-0.0042 4.2.2. High-performance liquid chromatography assay The reported analytical method gave a well-detectable linear response for the concentrations studied (500–15.6 µg/ml) as seen in Fig. 3 . R-squared or coefficient of determination (R2) of 0.9999 with a well-resolved diclofenac peak at 2 min elution (Fig. 2 ). The drug concentration can be calculated from the equation: A = 93696C + 321549 4.2. Dispersion Test Table 4 shows the results for all three brands and the results were as follows: G1 5 sec ± 0.63%, G2 5 sec ± 0.63%, and G3 5.16 sec ± 0.75%. These results, with average dispersion times around 5 sec and minimal variation, indicate that all of the brands studied meet the established criteria. 4.3. Friability The friability of G1, G2, and G3 was assessed by weighing 20 tablets before and after the process. Generally, a weight loss of less than 1% is considered acceptable for most products. The initial test results showed that G1 and G2 performed well, with weight losses of 0.62% and 0.94%, respectively, falling within the acceptable range. However, G3 initial test revealed a higher weight loss of 1.54%, exceeding the recommended limit. To ensure accuracy and rule out random variations, retests on G3 using two additional samples of 20 tablets each were undertaken. The retest results were significantly lower, with weight losses of 0.23% and 0.17%, respectively. By calculating the average weight loss across all three tests for G3 (0.064%) confirmed that it too met the acceptable friability criteria Table 4 . 4.4. Weight variation A weight variation test was conducted on the three generic diclofenac brands (G1, G2, and G3), and the results are presented in Table 4 . This test involved meticulously weighing 20 tablets from each brand and calculating the average weight and standard deviation. G1 showed an average weight of 304.10 ± 4.54 milligrams. G2 had an average weight of 198.91 ± 1.190 milligrams. Finally, G3 showed an average weight of 301.13 ± 1.048 milligrams. Generally, a weight variation of less than ± 5% from the average weight is considered acceptable. As evident from the results, all three brands fell within this limit. 4.5. Content uniformity and potency All brands contained (G1, G2, and G3) tablets formulated with diclofenac acid equivalent to 50 mg of diclofenac. A content uniformity test was conducted using 10 tablets from each brand. Individual tablets were extracted with methanolic sodium hydroxide 0.1 M and the concentration was measured after dilution using the previously mentioned HPLC method. Both G1 and G2 demonstrated acceptance values (AV) of 10.32 and 11.53, respectively, which fell within the acceptable range established by the USP. The requirements are met if the acceptance value of the first 10 dosage units is less than or equal to L1 (% i.e., ≤ 15) = However, the result for G3 was not compiled. The result of the first 10 tablets shows an AV of 21.35 and according to the USP, if the AV is greater than L1 (% i.e., > 15) then the test should be conducted on the next 20 units and the result of AV of the total 30 units was 11.56. For G3, the requirements were met because the final AV of the 30 dosage units was less than or equal to L1% (i.e., ≤ 15). The potency results shown in Table 4 demonstrate that all three brands comply with the USP specifications. This means the diclofenac content of each brand was within the acceptable range established by USP which typically falls between 90% and 110% of the labeled amount as seen in Table 5 . Table 5 Results of content uniformity. T value G2 100.0% T value G1 100.0% T value G3 100.0% T value G3 100.0% L1 15.0 L1 15.0 L1 15.0 L1 15.0 L2 25.0 L2 25.0 L2 25.0 L2 25.0 Average of 10 values 101 Average of 10 values 106.6 Average of 10 values 103.98 Average of 30 values 104.25 The standard deviation of 10 values 4.8 The standard deviation of 10 values 2.178 The standard deviation of 10 values 7.866 The standard deviation of 10 values 4.4 M = X-, (AV = Ks) 101 M = X-, (AV = Ks) 101.0 M value: (If X > 101.5%) 101.5 M value: (If X > 101.5%) 101.5 AV = Ks 11.53 AV = X -101.5 + Ks = (106.6-101.5) + 2.4 (2.78) 10.33 AV = X -101.5 + Ks = (103.98–101.5) + 2.4 (7.86) 21.35 AV = X -101.5 + Ks = (104.25–101.5) + 2.0 (4.4) 11.56 Result Pass Result Pass Result Fail Result Pass 4.6. In vitro dissolution In vitro dissolution testing was used to assess the release profiles of G1, G2, and G3. The USP (United States Pharmacopeia) establishes minimum requirements for the percentage of drug released S1: it should be not less than Q + 5% i.e and the Q of diclofenac sodium should be 75% of the labeled amount after 45 min. The results for G1 and G2 showed that all individual units tested passed the USP Acceptance criteria S1, as shown in Table 6 . However, the initial testing S1 for G3 tablets presented two out of six tablets did not achieve the minimum USP criteria; a repeat test was conducted on another six tablets of G3, and the results showed the average of the 12 tablets was 90.32%, which is more than 75%, and not less than 60%, which means it met the USP requirement at S2. Dissolution efficiency(DE) Figure 4 shows the dissolution profiles of the three generics of diclofenac tablets the average amount dissolved after 45 min was 105 ± 3.7, 95.2 ± 7.7, 90.3 ± 5.4 for G1, G2, and G3 tablets respectively. Results of calculated dissolution efficiencies show values as follows: G1, 78.83%; G2 72.23%; and G3, 67.50%. The similarity factor values(f2): According to US Food and Drug Administration (FDA) guidelines, a similarity coefficient (f2) value greater than 50 (50–100) indicates similarity of dissolution profiles [11]. G1 (Reference) and G2 with an f2 of 58.3 had similar dissolution profiles, while G3 had an f2 of 47.5 did not show a similar dissolution profile to the reference. Table 6 % Diclofenac dissolved from the tested products Stage Time (min) % Diclofenac dissolved G1 buffer stage at 6.8 Tablet 1 Tablet 2 Tablet3 Tablet 4 Tablet 5 Tablet 6 45 106٫12 99٫77 95٫15 114٫44 113٫80 91٫47 % Diclofenac dissolved G2 45 90٫03 95٫38 86٫16 100٫57 88٫79 97٫52 % Diclofenac dissolved G3 45 84٫69 83٫20 88٫80 92٫48 75٫97 70٫59 102٫83 99٫27 102٫81 79٫13 104٫80 99٫29 5. Discussion Achieving safe, stable, and effective therapy is the primary goal of developing the drug delivery system. For many years, oral drug delivery was the most preferred method. In current study, we evaluated the in vitro quality of three generic acid-free formulations of diclofenac equivalent to 50 mg of diclofenac sodium dispersible tablets commercially available in Saudi Arabia. Except for the borderline performance of one generic product(G3), all formulations have passed in vitro quality testing according to the US Pharmacopeia and European Pharmacopoeia. The potency results demonstrated that all three brands complied with USP specifications. Thus, the diclofenac content in each brand was within the acceptable range established by USP [10], which typically falls between 90% and 110% of the labeled amount. All brands demonstrated minimal weight variation, with average weights falling within the acceptable range of ± 5% from the mean. This ensures consistent dosing across tablets within each brand, which agrees with the results of a previous study on enteric-coated diclofenac tablets and sustained-release diclofenac sodium tablets [12–13] In addition, we found a remarkably rapid dispersion time of approximately 5 s for all of the three generic brands studied. This was significantly faster than the 3.25 to 3.75 min reported in an Indian study on dispersible tablets [14]. All the brands displayed acceptable friability and minimal weight loss. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with an additional sample. Notably, there is no monograph on dispersible diclofenac tablets; therefore, we used the dissolution criteria stated for delayed-release diclofenac tablets (buffer phase). G1 and G2 tablets passed the USP Acceptance criteria S1, as shown in Table 1 . However, the initial testing S1 for G3 tablets presented two out of six tablets did not achieve the minimum USP criteria; a repeat test was conducted on another six tablets of G3 and the result showed the average 12 tablets was (90.32%) more than 75% and not less than 60%, which means it met the USP requirement at S2. For comparison, the DE was calculated for the three generics. G1 showed the highest DE (78.83%), followed by G2 (72.23%) and G3 (67.50%). According to the Food and Drug Administration (FDA) guidelines, similarity factor values (f2) greater than 50 (50–100) [11] indicate similarity of the dissolution profiles; the reference product Voltaren-D is not yet available in the Saudi market. Therefore, we used the G1 dissolution data, which showed the highest DE, as the reference product for calculating the f2 ratio. G1 Reference and G2, had an f2 of 58.3. This meant they had similar dissolution profiles, whereas G3 with an f2 of 47.5 showed borderline performance. The quality of generic drug products marketed in Saudi Arabia is guaranteed by the present results, as well as the outcomes of multiple pre-marketing, post-marketing, and in vivo bioequivalence studies on the most popular pharmaceutical products. These findings highlight the importance of continuous monitoring of marketed formulations. 6. Conclusions We have evaluated the in vitro quality of three generic 50 mg diclofenac dispersible tablets commercially available on the Saudi market. All of the generics passed in vitro quality tests according to USP (41-NF 36). While all three generic brands (G1, G2, and G3) initially appeared to meet the USP standards, further testing with a larger sample size is needed for G3 to definitively confirm its compliance with the dissolution, friability, and content uniformity criteria. Further research should involve in vivo studies to assess the bioavailability and clinical effectiveness of these generic brands compared to the reference product. To guarantee the continued safety and efficacy of multisource medications, a robust national quality control system should prioritize post-marketing evaluation of drug performance. Declarations Ethics approval and consent to participate The study did not involve human or animal subjects. Not applicable Consent for publication Not applicable. Availability of data and materials Raw data are available from the corresponding author upon request. Competing interests The authors declare that they have no competing interests. Funding This study was supported by Researchers Supporting Project (number RSPD2024R622), King Saud University, Riyadh, Saudi Arabia. Authors' contributions All the authors contributed to the conception, design, and implementation of the study. The manuscript was drafted and critically revised by Samiah Alhabardi and Gamal Mahrous. 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Eight enteric-coated 50 mg diclofenac sodium tablet formulations marketed in Saudi Arabia: in vitro quality evaluation. BMC Res Notes. 2020;13(1):428. SHRIVASTAV S, RATHORE KS, PRASAD N. Formulation and evaluation of dispersible tablets of flavonoid pgal isolated from saraca asoca leaves. International journal of applied pharmaceutics. 2023; 125-130:125-130. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-4672508","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":330659636,"identity":"17c2a3d0-941e-4bb2-a0ce-11bbb3bd5bb5","order_by":0,"name":"Samiah Alhabardi¹","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYBAC+QbmNgbGBiDrMPNhiNABAloMDjDCtLAlE6mFAablAI8xkVrYD7Y9+LnDLp/vOM9nw59tDHJ8NxKYP/zAo0W+J7HdsPdMsuXMw7ybk3nbGIwlbySwSfbgs+ZAYpsEbxuzgQFQy2GgIxM3ALUw8ODTcv5hm+TftnqgFp7HB4EOqwdqYf74B5+WG4lt0rxth0FamBOADkswuJHAII3PFoMbD9ukZc8cN5A8zGZszHNOwnDmGaCIDD7v9ycfk3y7o9qA7/zhx5I/ymzk+Y4nH/74Bp/D0IAEEIOjaRSMglEwCkYBJQAAUTVSYC2QPskAAAAASUVORK5CYII=","orcid":"","institution":"King Saud University","correspondingAuthor":true,"prefix":"","firstName":"Samiah","middleName":"","lastName":"Alhabardi¹","suffix":""},{"id":330659637,"identity":"c43b2b3e-3b51-47d3-9d0d-b5d70767ad63","order_by":1,"name":"Gamal Mahrous¹","email":"","orcid":"","institution":"King Saud University","correspondingAuthor":false,"prefix":"","firstName":"Gamal","middleName":"","lastName":"Mahrous¹","suffix":""},{"id":330659638,"identity":"79a5d305-d28c-47ca-b2f0-17f856e6ce6b","order_by":2,"name":"Asma Alshahrani¹","email":"","orcid":"","institution":"King Saud University","correspondingAuthor":false,"prefix":"","firstName":"Asma","middleName":"","lastName":"Alshahrani¹","suffix":""},{"id":330659641,"identity":"02fed11b-fc28-4878-a55b-6d23930ce6f5","order_by":3,"name":"Ehab Taha","email":"","orcid":"","institution":"King Saud University","correspondingAuthor":false,"prefix":"","firstName":"Ehab","middleName":"","lastName":"Taha","suffix":""}],"badges":[],"createdAt":"2024-07-02 08:06:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4672508/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4672508/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":61310896,"identity":"0869697f-c01a-4dc7-b640-abfe888b7378","added_by":"auto","created_at":"2024-07-29 11:01:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28179,"visible":true,"origin":"","legend":"\u003cp\u003eCalibration curve of DS at 276 nm using UV Spectrophotometry.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4672508/v1/9b378aff0961bbf17ad71aee.png"},{"id":61310897,"identity":"69e982dc-af8a-47ae-a7b0-836163f5681f","added_by":"auto","created_at":"2024-07-29 11:01:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25392,"visible":true,"origin":"","legend":"\u003cp\u003eHPLC Chromatogram of DS.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4672508/v1/a79ca09eb92ea69ad0e4b1b9.png"},{"id":61310899,"identity":"e0164d0f-6b06-489b-a368-521d78458f5b","added_by":"auto","created_at":"2024-07-29 11:01:46","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45574,"visible":true,"origin":"","legend":"\u003cp\u003eCalibration curve of DS using HPLC assay.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4672508/v1/2a1a07a9dc029e33e024941d.png"},{"id":61310898,"identity":"3ed549aa-c693-424e-ae23-0fe90850787b","added_by":"auto","created_at":"2024-07-29 11:01:46","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26844,"visible":true,"origin":"","legend":"\u003cp\u003eDissolution profile for different Diclofenac generic tablets.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4672508/v1/e3716094f6fd69f403fb0e47.png"},{"id":61882749,"identity":"b5442491-31d5-4704-b2a3-f08e89f13e27","added_by":"auto","created_at":"2024-08-06 15:47:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":899862,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4672508/v1/85486732-8056-485d-9b07-a404e5131041.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eGenerics are medications that contain the same active ingredients and have the same effects as reference brand medications. There are several brands of generic medications on the market, all at reasonable costs, which reduce budgetary impact and facilitate the cost-effective use of available resources [1]. Moreover, in recent years, the Saudi government has been pushing for generic medication by distributing it at no cost to government hospitals. Manufacturers receive numerous benefits in exchange for producing less expensive medications. Therefore, the use of generic medications has increased globally in recent years [2]. In 2012, the global sales of generic drug products were valued at 67\u0026nbsp;billion USD and are predicted to increase to 99\u0026nbsp;billion USD by 2026. This represents a 32\u0026nbsp;billion USD increase in sales over the previous 14 years [3]. Similar to branded medications, generic medications must receive Saudi Food and Drug Authority (SFDA) approval to ensure their effectiveness. According to the SFDA, generic medications must meet the same high standards for purity, potency, and stability as branded medications. Bioequivalence testing was performed according to the manufacturer\u0026rsquo;s instructions [4]. Even though bioequivalence testing is required before generic drugs can be sold in Saudi Arabia, continuous evaluation is necessary to guarantee that the intended quality is upheld after marketing. Several generics in Saudi Arabia have passed the bioequivalence testing [5].\u003c/p\u003e \u003cp\u003eDiclofenac is one of the most widely used generic drugs in the Saudi Arabian market. Diclofenac is a non-steroidal anti-inflammatory medication (NSAIDs) used for the treatment and management of acute and chronic pain associated with inflammatory conditions, especially those involving the musculoskeletal system. Diclofenac is available in various tablet forms to suit the needs of different patients. These forms include modified-release, enteric-coated, and film-coated tablets; sustained-release tablets; and dispersible tablets. Diclofenac side effects include gastrointestinal (GI) irritation, wind or loss of appetite, mild rash, and severe stomach pain [6]. Severe stomach pain is the most undesirable side effect observed in these patients. Thus, dispersible tablet formulations can overcome GI problems; in such cases, administration of the dispersion prevents localization of the drug in the stomach.\u003c/p\u003e \u003cp\u003eDispersible tablets (DTs) are defined in the European Pharmacopeia as \u0026laquo;uncoated or film-coated tablets intended to be dispersed in water before administration to produce a homogeneous dispersion\u0026raquo; [7]. DTs are typically dispersed within 3 min in approximately 5 to 15 mL of water at 15 to 25\u0026deg;C [7]. Dispersible Tablets have several advantages such as ease of manufacturing and transportation, good physical and chemical stability, precise dosage and ease of administration which make them a great substitute for elderly and pediatric patients who struggle with swallowing [8]. In addition, they undergo rapid disintegration and absorption of medicines, which provides a rapid onset of action.\u003c/p\u003e \u003cp\u003e DTs differ from oral disintegrating tablets (ODTs) because they are tablets are designed to create a homogenous dispersion by dispersing in water before to administration. In contrast, ODTs are tablets that are placed in the mouth, where they break down quickly before being swallowed. DT therefore combines the advantages of a conventional tablet formulation (stability) with the ease of administration offered by a liquid formulation [9].\u003c/p\u003e \u003cp\u003eOur initial market research identified dispersible tablets (DTs) as potential areas for investigation. However, upon closer examination, we were surprised to find the need for the current study to specifically focus on dispersible tablets containing diclofenac in the Saudi market. This gap in knowledge provides valuable opportunities.\u003c/p\u003e \u003cp\u003eThis study has aimed to assess the quality of three generic diclofenac dispersible tablets (DT) available in the Saudi market. To achieve this objective, quality control studies were conducted based on the pharmacopeial criteria.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Chemicals and reagents\u003c/h2\u003e \u003cp\u003eDiclofenac sodium salt (DS) was purchased from Sigma-Aldrich (SIGMA, MO). Various local marketed generic diclofenac products (G1, G2, and G3), each containing 46.5 mg diclofenac acid equivalent to 50 mg diclofenac sodium salt were used as seen in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. All other chemicals and solvents were high-quality reagent grade.\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\u003eDiclofenac marked products in Saudi Arabia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProduct\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eManufacturer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eStrength\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBatch number/lot number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eManufacturing date\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExpiry Date\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSPIMACO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1144317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMAY 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMAY 2025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGLOBAL PHARMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 mg DT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eB254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAPRIL 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAPRIL 2025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJAMJOOM PHARMACEUTICALS COMPANY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eZN0184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDECEMBER 2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDECEMBER 2025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Calibration curve\u003c/h2\u003e\n \u003cp\u003eTwo assays were performed using UV spectrophotometry and HPLC.\u003c/p\u003e\n \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\n \u003ch2\u003e3.1.1. UV Spectrophotometric assay\u003c/h2\u003e\n \u003cp\u003eA Calibration curve was constructed in phosphate buffer (pH 6.8), and 50 mg of DS was accurately weighed using an analytical balance (Model no. B203-S, Mettler Toledo, Switzerland). DS powder was dissolved in 50 ml methanol (1000 \u0026micro;g/ml) to form a stock solution. Different concentrations: (3,6,9,12,15, and 18 \u0026micro;g/ml) were made using phosphate buffer at pH 6.8 and measured at 276 nm wavelength against a blank using UV spectroscopy. Their absorbance was plotted against corresponding concentration to construct a calibration curve.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\n \u003ch2\u003e3.1.2. High-performance liquid chromatography (HPLC) assay\u003c/h2\u003e\n \u003cp\u003eThe method described in USP 41 was followed with some modifications. The mobile phase was consisting of an isocratic mixture of acetonitrile and 0.1 M ammonium acetate solution in a ratio of 1:1 (v/v). The mobile phase was prepared fresh each day for analysis, filtered through a 0.45 \u0026micro;m Millipore filter and degassed by sonication before experimenting. For the analysis of DS samples, 50 \u0026micro;l of each sample was injected into HPLC Waters system consisting of an Autosampler (model no. 717) (plus), pump model (no. 1525), and Dual \u0026lambda; Absorbance UV detector model (no. 2487) that adjusted at 276 nm. DS separation was performed using (Nova-Pak\u0026reg;) column (C18, 4 \u0026micro;m, 3.9 \u0026times; 250 mm). The column temperature was kept at 29\u0026deg;C during the analysis, and the flow rate was adjusted at 1 ml/min [10].\u003c/p\u003e\n \u003cp\u003eThe calibration curve was constructed by accurately weighing 50 mg of DS using an analytical balance (Model (No. B203-S, Mettler Toledo, Switzerland) and dissolved in 50 ml methanol (1000 \u0026micro;g/ml). Serial dilutions were prepared in different concentrations (15.6, 31, 62.5, 125, 250, and 500 \u0026micro;g/ml) and were measured using HPLC using the above-mentioned method.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. Quality control tests\u003c/h2\u003e\n \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n \u003ch2\u003e3.2.1. Physicochemical characteristics\u003c/h2\u003e\n \u003cdiv id=\"Sec10\" class=\"Section4\"\u003e\n \u003ch2\u003e3.2.1.1. Hardness, Thickness and Diameter\u003c/h2\u003e\n \u003cp\u003eA hardness tester (EH01P, Electrolab, India) was used in order to assess the strength of each tablet. A single tablet was positioned between the jaws of the device, and the force was gradually increased until the tablet broke. The breaking point indicated the breaking strength of the tablet. Hardness tests were conducted using 10 tablets of each brand. The thickness and diameter were measured using a micrometer (M\u0026amp;W, Sheffield, England) on twenty tablets from each of the three brands studied. The average value of each dimension was recorded.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec11\" class=\"Section4\"\u003e\n \u003ch2\u003e3.2.1.2. Dispersibility\u003c/h2\u003e\n \u003cp\u003eDispersibility is a physical process related to the mechanical breakdown of a tablet or granulated particles into smaller particles, representing the breakage of interparticle interactions generated during tablet compaction of granulated particles of the active pharmaceutical ingredient (API) and excipients. Generally, after a liquid wets the tablet surface and penetrates the pores, it breaks down into smaller particles and disintegrates.\u003c/p\u003e\n \u003cp\u003eDispersibility is a physical process involving the mechanical breakdown of interparticle interactions created during compression of the tablet which result in smaller particles and disintegrates. This process occurs when liquid wets the tablet surface and enters the pores inside tablets. The criteria of dispersible tablets are to disintegrate within 3 min by using water at 15\u0026ndash;25\u0026deg;C. To test the dispersibility, one tablet was placed in 25 ml of water and stirred until it was completely dispersed. The test was repeated using six tablets of each brand [7].\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n \u003ch2\u003e3.2.2. Friability\u003c/h2\u003e\n \u003cp\u003eThe stability of tablets is determined according to USP41-NF36. Briefly, 20 tablets were weighed (W1) and place them in the friability instrument (Erweka, TA3R, Heusenstamm, Germany) and they rotated at 25 rpm for 4 minutes. Then, the tablets were weighed again after removing the residue (W2) and the friability was calculated as follows:\u003c/p\u003e\n \u003cp\u003e% Friability\u0026thinsp;=\u0026thinsp;100\u0026times; (W1\u0026thinsp;\u0026minus;\u0026thinsp;W2)/W1 (Eq.\u0026nbsp;1)\u003c/p\u003e\n \u003cp\u003eFor tablet unit weight equal to or less than 650 mg, take a sample of whole tablets as near as possible to 6.5 g [10].\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\n \u003ch2\u003e3.2.3. Weight variation\u003c/h2\u003e\n \u003cp\u003eA weight-variation test was performed to ensure uniformity in the weight of the prepared tablets. Twenty tablets from each formulation batch were randomly selected and accurately weighed one by one using a digital scale, and their average weights were calculated and recorded as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\n \u003ch2\u003e3.2.4. Content uniformity\u003c/h2\u003e\n \u003cp\u003eContent uniformity was determined by taking a sample of not less than (NLT) 30 tablets. Ten units were individually assayed as directed in the individual monograph assay. The requirements are met USP41-NF36 if the acceptance value of the first 10 dosage units is less than or equal to L1% (i.e. \u0026ge;15). If the acceptance value was greater than L1(%, i.e., \u0026gt; 15), the next 20 units were tested. The requirements are met if the final acceptance value of the 30 dosage units is less than or equal to L1%(i.e. \u0026ge;15) and all individual dosage units fall within the range [1+(0.01) (L2)]M to [1(0.01) (L2)] M. I. no dosage unit result can be less than [1-(0.01) (L2)] M while on the high side no dosage unit result can be greater than [1+(0.01) (L2)]. SP41-NF36 (10). The acceptance value (AV) was calculated using the following formula:\u003c/p\u003e\n \u003cp\u003eAV = (M-X-)\u0026thinsp;+\u0026thinsp;ks ( Eq.\u0026nbsp;2)\u003c/p\u003e\n \u003cp\u003eWhere, k\u0026thinsp;=\u0026thinsp;acceptability constant.\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;sample size (no. of units):\u003c/p\u003e\n \u003cp\u003eif n\u0026thinsp;=\u0026thinsp;10 then k\u0026thinsp;=\u0026thinsp;2.4\u003c/p\u003e\n \u003cp\u003eif n\u0026thinsp;=\u0026thinsp;30 then k\u0026thinsp;=\u0026thinsp;2.0\u003c/p\u003e\n \u003cp\u003es\u0026thinsp;=\u0026thinsp;sample standard deviation.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; M= Reference\u003c/p\u003e\n \u003cp\u003eTable 2: Acceptability value conditions for content uniformity\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"445\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92134831460674%\" valign=\"top\"\u003e\n \u003cp\u003eConditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"57.07865168539326%\" valign=\"top\"\u003e\n \u003cp\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92134831460674%\" valign=\"top\"\u003e\n \u003cp\u003eif 98.5% \u0026le; X- \u0026le; 101.5 %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"57.07865168539326%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;M = X-, (AV = Ks)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92134831460674%\" valign=\"top\"\u003e\n \u003cp\u003eIf X- \u0026lt; 98.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"57.07865168539326%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;M = 98.5%, (AV = 98.5-X- +Ks)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.92134831460674%\" valign=\"top\"\u003e\n \u003cp\u003eIf X- \u0026gt; 101.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"57.07865168539326%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;M = 101.5%, (AV=X\u0026ndash; -101.5+Ks)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.2.5. Chemical potency\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eWe evaluated the chemical\u0026nbsp;potency by taking a sample of 10 tablets from each brand, grinding them together, and then measuring a portion equivalent to the average tablet weight. For a product to be considered acceptable, its weight should be within 90% to 110% of the amount stated on the label [10].\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.2.6. In vitro dissolution\u003c/p\u003e\n \u003cp\u003eDissolution test is one of the standard requirements for the tablets to evaluate the\u0026nbsp;drug release. The dissolution test was performed according to USP 41-NF 36 using (apparatus 2 (DT-70 dissolution test instrument, manufactured by (Pharma Test, Germany). The paddle was driven at 50 rpm in 900 ml of phosphate buffer (pH 6.75\u0026ndash;6.85). Medium samples were withdrawn at 5, 10, 15, 20, 30, and 45 min. The amount of diclofenac dissolved in the dissolution medium was determined using spectrophotometry at\u0026nbsp;a wavelength of 276 nm.\u0026nbsp;Phosphate buffer\u0026nbsp;(pH 6.8) was prepared by mixing sodium dihydrogen\u0026nbsp;phosphate (ROMIL UK) 34\u0026nbsp;g, and sodium hydroxide (Loba Chemie India) 4.5 g in a volumetric flask containing 5 L distilled water.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;The dissolution efficiency (DE) was calculated according to the following formula: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cimg 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\"\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Results","content":"\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Physicochemical characteristics\u003c/h2\u003e \u003cp\u003eColor: A white color.\u003c/p\u003e \u003cp\u003eOdor: Clean and neutral, with no detectable odor.\u003c/p\u003e \u003cp\u003eShape: Square for G1, round for G3 and G2.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the main result.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIn-vitro quality tests of three generic dispersible tablets containing diclofenac available on the Saudi market.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHardness\u003c/p\u003e \u003cp\u003e(Kp)\u003c/p\u003e \u003cp\u003emean\u003c/p\u003e \u003cp\u003e(\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThickness\u003c/p\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003cp\u003emean\u003c/p\u003e \u003cp\u003e(\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDiameter\u003c/p\u003e \u003cp\u003e(mm)\u003c/p\u003e \u003cp\u003emean (\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDispersion Test\u003c/p\u003e \u003cp\u003e(sec)\u003c/p\u003e \u003cp\u003emean (\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFriability\u003c/p\u003e \u003cp\u003e% loss\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;20 or 60\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eWeight variation\u003c/p\u003e \u003cp\u003e(mg)\u003c/p\u003e \u003cp\u003emean (\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;20\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePotency\u003c/p\u003e \u003cp\u003eAverage content\u003c/p\u003e \u003cp\u003e%))\u003c/p\u003e \u003cp\u003emean (\u0026plusmn;\u0026thinsp;SD%)\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;10\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\u003eG1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.07 (0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.50(0.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.1(0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.62%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e304٫10(4.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e106٫5%(2.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eG2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.015(0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.53(0.005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.02(0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.94%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e198٫91(1.190)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e105٫4%(4.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eG3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.87(0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.53(0.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.50(0.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.16(0.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.64%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e301٫13(1.048)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e104٫2%(4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e4.1.1. Hardness, thickness, and diameter\u003c/h2\u003e \u003cp\u003eThe hardness values of all three generic brands (G1, G2, and G3) met the established acceptance criteria (4\u0026ndash;8 kp) for uncoated tablets. The individual crushing strengths measurements were 6.07(0.3), 6.015(0.2) and 5.87(0.4), for G1, G2, and G3 respectively. Statistical evaluation of the diameter was performed to determine the diameter consistency of G1, G2, and G3. The analysis revealed minimal variation, with average values of 10.1(0.01), 8.02(0.05) and 9.50(0.08), respectively. This uniformity ensures that all of the brands comply with the stringent quality control standards.\u003c/p\u003e \u003cp\u003eThe thickness should be controlled within \u0026plusmn;\u0026thinsp;5% variation of standard value, and the results showed G1 4.50(0.006), G2 3.53(0.005), and G3 4.53(0.006) fell within the acceptable range of \u0026plusmn;\u0026thinsp;5% variation from the average value as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Calibration curves\u003c/h2\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003e4.2.1. UV Spectrophotometric assay\u003c/h2\u003e \u003cp\u003eThe absorbance was linear over the concentration range (21\u0026ndash;3 \u0026micro;g/ml) R-squared as seen in Figure (1). We also determined the coefficient of determination (R2\u0026thinsp;=\u0026thinsp;0.999). The drug concentration was calculated using the following equation:\u003c/p\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;0.0356C-0.0042\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003e4.2.2. High-performance liquid chromatography assay\u003c/h2\u003e \u003cp\u003eThe reported analytical method gave a well-detectable linear response for the concentrations studied (500\u0026ndash;15.6 \u0026micro;g/ml) as seen in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. R-squared or coefficient of determination (R2) of 0.9999 with a well-resolved diclofenac peak at 2 min elution (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The drug concentration can be calculated from the equation:\u003c/p\u003e \u003cp\u003eA\u0026thinsp;=\u0026thinsp;93696C\u0026thinsp;+\u0026thinsp;321549\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Dispersion Test\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the results for all three brands and the results were as follows: G1 5 sec\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63%, G2 5 sec\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63%, and G3 5.16 sec\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75%. These results, with average dispersion times around 5 sec and minimal variation, indicate that all of the brands studied meet the established criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003e4.3. Friability\u003c/h2\u003e \u003cp\u003eThe friability of G1, G2, and G3 was assessed by weighing 20 tablets before and after the process. Generally, a weight loss of less than 1% is considered acceptable for most products. The initial test results showed that G1 and G2 performed well, with weight losses of 0.62% and 0.94%, respectively, falling within the acceptable range. However, G3 initial test revealed a higher weight loss of 1.54%, exceeding the recommended limit. To ensure accuracy and rule out random variations, retests on G3 using two additional samples of 20 tablets each were undertaken. The retest results were significantly lower, with weight losses of 0.23% and 0.17%, respectively. By calculating the average weight loss across all three tests for G3 (0.064%) confirmed that it too met the acceptable friability criteria Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003e4.4. Weight variation\u003c/h2\u003e \u003cp\u003eA weight variation test was conducted on the three generic diclofenac brands (G1, G2, and G3), and the results are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e. This test involved meticulously weighing 20 tablets from each brand and calculating the average weight and standard deviation. G1 showed an average weight of 304.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.54 milligrams. G2 had an average weight of 198.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.190 milligrams. Finally, G3 showed an average weight of 301.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.048 milligrams. Generally, a weight variation of less than \u0026plusmn;\u0026thinsp;5% from the average weight is considered acceptable. As evident from the results, all three brands fell within this limit.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003e4.5. Content uniformity and potency\u003c/h2\u003e \u003cp\u003eAll brands contained (G1, G2, and G3) tablets formulated with diclofenac acid equivalent to 50 mg of diclofenac. A content uniformity test was conducted using 10 tablets from each brand. Individual tablets were extracted with methanolic sodium hydroxide 0.1 M and the concentration was measured after dilution using the previously mentioned HPLC method. Both G1 and G2 demonstrated acceptance values (AV) of 10.32 and 11.53, respectively, which fell within the acceptable range established by the USP. The requirements are met if the acceptance value of the first 10 dosage units is less than or equal to L1 (% i.e., \u0026le;\u0026thinsp;15)\u0026thinsp;=\u0026thinsp;However, the result for G3 was not compiled. The result of the first 10 tablets shows an AV of 21.35 and according to the USP, if the AV is greater than L1 (% i.e., \u0026gt; 15) then the test should be conducted on the next 20 units and the result of AV of the total 30 units was 11.56. For G3, the requirements were met because the final AV of the 30 dosage units was less than or equal to L1% (i.e., \u0026le;\u0026thinsp;15). The potency results shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e4\u003c/span\u003e demonstrate that all three brands comply with the USP specifications. This means the diclofenac content of each brand was within the acceptable range established by USP which typically falls between 90% and 110% of the labeled amount as seen in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of content uniformity.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT value\u003c/p\u003e \u003cp\u003eG2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.0%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT value\u003c/p\u003e \u003cp\u003eG1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT value\u003c/p\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100.0%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT value\u003c/p\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e100.0%\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\u003eL1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eL1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eL1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eL1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eL2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eL2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eL2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eL2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAverage of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eAverage of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAverage of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e103.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eAverage of 30 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e104.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe standard deviation of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eThe standard deviation of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eThe standard deviation of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.866\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eThe standard deviation of 10 values\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eM\u0026thinsp;=\u0026thinsp;X-, (AV\u0026thinsp;=\u0026thinsp;Ks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eM\u0026thinsp;=\u0026thinsp;X-, (AV\u0026thinsp;=\u0026thinsp;Ks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eM value: (If X\u0026thinsp;\u0026gt;\u0026thinsp;101.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e101.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eM value: (If X\u0026thinsp;\u0026gt;\u0026thinsp;101.5%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e101.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAV\u0026thinsp;=\u0026thinsp;Ks\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eAV\u0026thinsp;=\u0026thinsp;X -101.5\u0026thinsp;+\u0026thinsp;Ks = (106.6-101.5)\u0026thinsp;+\u0026thinsp;2.4 (2.78)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eAV\u0026thinsp;=\u0026thinsp;X -101.5\u0026thinsp;+\u0026thinsp;Ks = (103.98\u0026ndash;101.5)\u0026thinsp;+\u0026thinsp;2.4 (7.86)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eAV\u0026thinsp;=\u0026thinsp;X -101.5\u0026thinsp;+\u0026thinsp;Ks = (104.25\u0026ndash;101.5)\u0026thinsp;+\u0026thinsp;2.0 (4.4)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eResult\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eResult\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eResult\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFail\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eResult\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePass\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003e4.6. In vitro dissolution\u003c/h2\u003e \u003cp\u003eIn vitro dissolution testing was used to assess the release profiles of G1, G2, and G3. The USP (United States Pharmacopeia) establishes minimum requirements for the percentage of drug released S1: it should be not less than Q\u0026thinsp;+\u0026thinsp;5% i.e and the Q of diclofenac sodium should be 75% of the labeled amount after 45 min. The results for G1 and G2 showed that all individual units tested passed the USP Acceptance criteria S1, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e6\u003c/span\u003e. However, the initial testing S1 for G3 tablets presented two out of six tablets did not achieve the minimum USP criteria; a repeat test was conducted on another six tablets of G3, and the results showed the average of the 12 tablets was 90.32%, which is more than 75%, and not less than 60%, which means it met the USP requirement at S2.\u003c/p\u003e \u003cp\u003eDissolution efficiency(DE)\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the dissolution profiles of the three generics of diclofenac tablets the average amount dissolved after 45 min was 105\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7, 95.2\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7, 90.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 for G1, G2, and G3 tablets respectively.\u003c/p\u003e \u003cp\u003eResults of calculated dissolution efficiencies show values as follows: G1, 78.83%; G2 72.23%; and G3, 67.50%.\u003c/p\u003e \u003cp\u003eThe similarity factor values(f2):\u003c/p\u003e \u003cp\u003e According to US Food and Drug Administration (FDA) guidelines, a similarity coefficient (f2) value greater than 50 (50\u0026ndash;100) indicates similarity of dissolution profiles [11].\u003c/p\u003e \u003cp\u003eG1 (Reference) and G2 with an f2 of 58.3 had similar dissolution profiles, while G3 had an f2 of 47.5 did not show a similar dissolution profile to the reference.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e% Diclofenac dissolved from the tested products\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTime\u003c/p\u003e \u003cp\u003e(min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003e% Diclofenac dissolved\u003c/p\u003e \u003cp\u003eG1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u003cb\u003ebuffer stage at 6.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTablet 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTablet 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTablet3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTablet 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTablet 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTablet 6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106٫12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99٫77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95٫15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e114٫44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e113٫80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e91٫47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003e% Diclofenac dissolved\u003c/p\u003e \u003cp\u003eG2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90٫03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95٫38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86٫16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100٫57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e88٫79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e97٫52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c8\" namest=\"c2\"\u003e \u003cp\u003e% Diclofenac dissolved\u003c/p\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84٫69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83٫20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88٫80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e92٫48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e75٫97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e70٫59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102٫83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e99٫27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102٫81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79٫13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e104٫80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e99٫29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"5. Discussion","content":"\u003cp\u003eAchieving safe, stable, and effective therapy is the primary goal of developing the drug delivery system. For many years, oral drug delivery was the most preferred method. In current study, we evaluated the in vitro quality of three generic acid-free formulations of diclofenac equivalent to 50 mg of diclofenac sodium dispersible tablets commercially available in Saudi Arabia. Except for the borderline performance of one generic product(G3), all formulations have passed in vitro quality testing according to the US Pharmacopeia and European Pharmacopoeia.\u003c/p\u003e \u003cp\u003eThe potency results demonstrated that all three brands complied with USP specifications. Thus, the diclofenac content in each brand was within the acceptable range established by USP [10], which typically falls between 90% and 110% of the labeled amount. All brands demonstrated minimal weight variation, with average weights falling within the acceptable range of \u0026plusmn;\u0026thinsp;5% from the mean. This ensures consistent dosing across tablets within each brand, which agrees with the results of a previous study on enteric-coated diclofenac tablets and sustained-release diclofenac sodium tablets [12\u0026ndash;13] In addition, we found a remarkably rapid dispersion time of approximately 5 s for all of the three generic brands studied. This was significantly faster than the 3.25 to 3.75 min reported in an Indian study on dispersible tablets [14].\u003c/p\u003e \u003cp\u003eAll the brands displayed acceptable friability and minimal weight loss. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with an additional sample.\u003c/p\u003e \u003cp\u003eNotably, there is no monograph on dispersible diclofenac tablets; therefore, we used the dissolution criteria stated for delayed-release diclofenac tablets (buffer phase). G1 and G2 tablets passed the USP Acceptance criteria S1, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eHowever, the initial testing S1 for G3 tablets presented two out of six tablets did not achieve the minimum USP criteria; a repeat test was conducted on another six tablets of G3 and the result showed the average 12 tablets was (90.32%) more than 75% and not less than 60%, which means it met the USP requirement at S2. For comparison, the DE was calculated for the three generics. G1 showed the highest DE (78.83%), followed by G2 (72.23%) and G3 (67.50%).\u003c/p\u003e \u003cp\u003e According to the Food and Drug Administration (FDA) guidelines, similarity factor values (f2) greater than 50 (50\u0026ndash;100) [11] indicate similarity of the dissolution profiles; the reference product Voltaren-D is not yet available in the Saudi market. Therefore, we used the G1 dissolution data, which showed the highest DE, as the reference product for calculating the f2 ratio. G1 Reference and G2, had an f2 of 58.3. This meant they had similar dissolution profiles, whereas G3 with an f2 of 47.5 showed borderline performance.\u003c/p\u003e \u003cp\u003eThe quality of generic drug products marketed in Saudi Arabia is guaranteed by the present results, as well as the outcomes of multiple pre-marketing, post-marketing, and in vivo bioequivalence studies on the most popular pharmaceutical products. These findings highlight the importance of continuous monitoring of marketed formulations.\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eWe have evaluated the in vitro quality of three generic 50 mg diclofenac dispersible tablets commercially available on the Saudi market. All of the generics passed in vitro quality tests according to USP (41-NF 36). While all three generic brands (G1, G2, and G3) initially appeared to meet the USP standards, further testing with a larger sample size is needed for G3 to definitively confirm its compliance with the dissolution, friability, and content uniformity criteria. Further research should involve in vivo studies to assess the bioavailability and clinical effectiveness of these generic brands compared to the reference product. To guarantee the continued safety and efficacy of multisource medications, a robust national quality control system should prioritize post-marketing evaluation of drug performance.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study did not involve human or animal subjects. Not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRaw data are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Researchers Supporting Project (number RSPD2024R622), King Saud University, Riyadh, Saudi Arabia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors contributed to the conception, design, and implementation of the study. The manuscript was drafted and critically revised by Samiah Alhabardi and Gamal Mahrous.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Researchers Supporting Project (number RSPD2024R622), King Saud University, Riyadh, Saudi Arabia.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAnonymous. Access to new medicines in Europe: technical review of policy initiatives and opportunities for collaboration and research. WHO Regional Office for Europe. 2015. https://apps.who.int/iris/handle/10665 /159405.\u003c/li\u003e\n \u003cli\u003e\u003cspan dir=\"LTR\"\u003eAlrasheedy A, Hassali MA, Stewart K, Kong D, Aljadhey H, Ibrahim MIM, Al-Tamimi S. Patient knowledge, perceptions, and acceptance of generic medicines: a comprehensive review of the current literature. Patient Intell. 2014; 6:1-29.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003eAnonymous. Worldwide generic prescription drug sales 2012-2026. https://www.statista.com/statistics/309411/global-total-generic-prescription-drug-revenue/\u003c/li\u003e\n \u003cli\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;Supporting Pharmaceutical Manufacturers: A Summary of SFDA Guidance on Vaccines and Generic Drugs.\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\"\u003ehttps://istitlaa.ncc.gov.sa\u003c/span\u003e\u003cspan dir=\"LTR\"\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan dir=\"LTR\"\u003eRegulatory Framework for Drugs Approval.2021;\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\"\u003eHttps://www.sfda.gov.sa/sites/default/files/2021-10/RegulatoryFramework_1.pdf\u003c/span\u003e\u003cspan dir=\"LTR\"\u003e.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan dir=\"LTR\"\u003eDiclofenac. 2021;\u003c/span\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan dir=\"LTR\"\u003ehttps://www.nhs.uk/medicines/diclofenac/\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003eEuropean Pharmacopeia Commission. European Pharmacopeia. 6th ed. Council of Europe; 2007.\u003c/li\u003e\n \u003cli\u003e\u003cspan dir=\"LTR\"\u003e[8] Dey P, Maiti S. Orodispersible tablets: A new trend in drug delivery. J Nat Sci Biol Med. 2010;1(1):2-5.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003eAher S, Saudagar RB, Shinde M. Review: fast dissolving tablet. International journal of current pharmaceutical research. 2018; V10 N2 (2018 03 01): 5-12.\u003c/li\u003e\n \u003cli\u003ePharmacopeia online. USP32. https://www.uspbpep.com/usp32/ pub/data/v32270/usp32nf27s0_m24972.html#usp32nf27s0_m24972.\u003c/li\u003e\n \u003cli\u003eOffice of Training and Communications Division of Communications Management the Drug Information Branch.1997;http://www.fda.gov/cder/guidance.htm.\u003c/li\u003e\n \u003cli\u003eHammami MM, AlSwayeh R, Hussein RF. Pharmaceutical quality of seven brands of diclofenac tablet on the Saudi market. BMC Res Notes. 2020;13(1):548.\u003c/li\u003e\n \u003cli\u003eHammami MM, Hussein RF, AlSwayeh R, Alvi SN. Eight enteric-coated 50 mg diclofenac sodium tablet formulations marketed in Saudi Arabia: in vitro quality evaluation. BMC Res Notes. 2020;13(1):428.\u003c/li\u003e\n \u003cli\u003eSHRIVASTAV S, RATHORE KS, PRASAD N. Formulation and evaluation of dispersible tablets of flavonoid pgal isolated from saraca asoca leaves. International journal of applied pharmaceutics. 2023; 125-130:125-130.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"diclofenac, generic brands, dispersible tablets, Saudi market, and quality control.","lastPublishedDoi":"10.21203/rs.3.rs-4672508/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4672508/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe fundamental objective in developing any drug delivery approach is to achieve effective and safe therapy. Medications classified as generics are those that contain the same active ingredients and have the same quality as the reference medications. Several generic drugs are available on the market, all at a reasonable cost. In this study, the quality of Three generic brands of diclofenac dispersible tablets (DT) available in the Saudi market was assessed, namely: G1 and G2, and G3.\u003c/p\u003e\n\u003cp\u003eExcept for the borderline performance of one generic formulation (G3), all formulations passed in vitro quality tests according to the United States Pharmacopoeia. According to the US Pharmacopoeia, every generic formulation passed in vitro quality tests, except for one generic formulation (G3) that performed inconclusively. All brands demonstrated minimal weight variation, with average weights falling within the acceptable range of ±5% from the mean and a rapid dispersion time of around 5 sec. All the brands displayed acceptable friability and minimal weight loss. The potency results demonstrated that all of the three brands complied with United States Pharmacopeia (USP) specifications, which typically fall between 90% and 110% of the labeled amount. G1 and G2 passed the content uniformity test in their first attempt. G3 initially failed the content uniformity test but passed upon retesting with additional samples. G1 and G2 tablets passed the USP Acceptance criteria in stage one, and G3 tablets met the requirements in stage two. G1 showed the highest DE (%78.83), followed by G2 (%72.23), and G3 (%67.50). The G1 dissolution data, which showed the highest dissolution efficiency, were used as the reference product to calculate the similarity factor (f2 (ratio. G1 (Reference) and G2 with an f2 of (58.3) have similar dissolution profiles. G3, with an f2 of (47.5) showed borderline performance. This study highlights the importance of post-marketing evaluations of generic drugperformance.\u003c/p\u003e","manuscriptTitle":"Pharmaceutical quality of dispersible diclofenac tablets in the Saudi market","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-29 11:01:41","doi":"10.21203/rs.3.rs-4672508/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bf0c10bf-20b8-43cd-96f1-8343041d5795","owner":[],"postedDate":"July 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-06T15:39:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-29 11:01:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4672508","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4672508","identity":"rs-4672508","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}