Xiao-Dong Fan, Shengying Shi, Junlin He, Jia Deng, Jingou Ji
The aim of this study was to develop a method for set up and optimization of a pH-gradient biphasic dissolution model by orthogonal test design in light of the correlation with published in vivo data of ketoconazole (KTZ). A pH-gradient biphasic dissolution test was designed with a sequential pH-gradient in the aqueous phase to simulate stomach, duodenum, jejunum, and ileum, and the organic phase was added in simulated small intestine conditions. The model was optimized by orthogonal test design with three factors and three levels and correlating with the published pharmacokinetic data of pure drug. The optimized dissolution conditions were 30 rpm, 100 mL of an organic volume, and pH 5.5, 6.5, and 6.8 in the pH-gradient aqueous phase in USP apparatus 2. Under these conditions, KTZ dissolution displayed a good linear relationship with in vivo absorption (R2 = 0.85). This study indicates that this methodology is feasible to develop an in vivo predictive dissolution test.
{"title":"Development of In Vivo Predictive pH-Gradient Biphasic Dissolution Test for Weakly Basic Drugs: Optimization by Orthogonal Design","authors":"Xiao-Dong Fan, Shengying Shi, Junlin He, Jia Deng, Jingou Ji","doi":"10.14227/dt280321p24","DOIUrl":"https://doi.org/10.14227/dt280321p24","url":null,"abstract":"The aim of this study was to develop a method for set up and optimization of a pH-gradient biphasic dissolution model by orthogonal test design in light of the correlation with published in vivo data of ketoconazole (KTZ). A pH-gradient biphasic dissolution test was designed with a sequential pH-gradient in the aqueous phase to simulate stomach, duodenum, jejunum, and ileum, and the organic phase was added in simulated small intestine conditions. The model was optimized by orthogonal test design with three factors and three levels and correlating with the published pharmacokinetic data of pure drug. The optimized dissolution conditions were 30 rpm, 100 mL of an organic volume, and pH 5.5, 6.5, and 6.8 in the pH-gradient aqueous phase in USP apparatus 2. Under these conditions, KTZ dissolution displayed a good linear relationship with in vivo absorption (R2 = 0.85). This study indicates that this methodology is feasible to develop an in vivo predictive dissolution test.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorge A. García, María R. Bendezú, Mario Pineda-Pérez, A. M. Muñoz, María Saravia, Angel T. Alvarado
Dissolution studies have evolved from quality control testing to being an indicator of biopharmaceutical performance and an alternative to in vivo bioequivalence and interchangeability studies in clinical practice. The critical quality attributes and in vitro bioequivalence of two generic formulations of amlodipine (5-mg tablets, A and B) were compared to the reference (Ref) drug. Amlodipine tablets available in Ica, Peru belong to class 1. The study evaluated weight, hardness, friability, and content of the tablets. USP apparatus 2 was used with 900 mL of dissolution medium at pH 1.2, 4.5, and 6.8. 5 (100 rpm, 37 ± 0.5 °C). Samples (5 mL) were withdrawn at 5, 10, 15, 20, 25, 30, 45, and 60 min and analyzed at 239 nm on a spectrophotometer. The dissolution percentages at pH 4.5 and 6.8 were less than 85% at 30 min for all three products; at pH 1.2, more than 85% was released in less than 15 min (Ref: 101.6%; A: 98.5%, B: 89.9%). The similarity factors were 51.2–64.3; dissolution efficiency was 84.5–96.5%, and mean dissolution time was 4.5–12.4 min. According to these parameters, generic formulations A and B demonstrated in vitro bioequivalence to the reference drug.
{"title":"Quality Attributes and In Vitro Bioequivalence of Amlodipine (5 mg) Tablets in Ica, Peru","authors":"Jorge A. García, María R. Bendezú, Mario Pineda-Pérez, A. M. Muñoz, María Saravia, Angel T. Alvarado","doi":"10.14227/dt280421pgc1","DOIUrl":"https://doi.org/10.14227/dt280421pgc1","url":null,"abstract":"Dissolution studies have evolved from quality control testing to being an indicator of biopharmaceutical performance and an alternative to in vivo bioequivalence and interchangeability studies in clinical practice. The critical quality attributes and in vitro bioequivalence of two generic formulations of amlodipine (5-mg tablets, A and B) were compared to the reference (Ref) drug. Amlodipine tablets available in Ica, Peru belong to class 1. The study evaluated weight, hardness, friability, and content of the tablets. USP apparatus 2 was used with 900 mL of dissolution medium at pH 1.2, 4.5, and 6.8. 5 (100 rpm, 37 ± 0.5 °C). Samples (5 mL) were withdrawn at 5, 10, 15, 20, 25, 30, 45, and 60 min and analyzed at 239 nm on a spectrophotometer. The dissolution percentages at pH 4.5 and 6.8 were less than 85% at 30 min for all three products; at pH 1.2, more than 85% was released in less than 15 min (Ref: 101.6%; A: 98.5%, B: 89.9%). The similarity factors were 51.2–64.3; dissolution efficiency was 84.5–96.5%, and mean dissolution time was 4.5–12.4 min. According to these parameters, generic formulations A and B demonstrated in vitro bioequivalence to the reference drug.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samah A. Ata, O. Tarawneh, Rana Sejare, Suhair Sunoqrot, Rania A. Al-Qirim
The objective of this study was to investigate the effect of physiological conditions on the dissolution rate of acetylsalicylic acid (ASA) from two commercial brands compared against compendial tests. All parameters of the analysis were chosen according to ICH (Q2(R1)) guidelines and were validated statistically. The maximum wavelength (λmax) and absorptivity (ε) for ASA were determined in different solvents at different pH values (6.8 and 4.9) by a validated UV-Vis spectrophotometric method. When ethanol (EtOH) was used as co-solvent, ε was found to be 3.15, and when 0.1 N NaOH was used, ε was 18.50. Dissolution tests were conducted according to pharmacopeia specifications; however, the lack of a direct specification in determining ε in the pharmacopeia has permitted enormous probabilities of employing different solvents. Herein, when NaOH was used to dissolve ASA, ε was calculated to be 18.50, and upon conducting compendial dissolution tests for enteric-coated tablets, only 20% of ASA was released after 4 h. When analyzing the same data using ε of 3.15 (calculated from dissolving ASA in EtOH), the amount of released ASA was found to be 95% after 2 h. Furthermore, the effect of a fed and fasted state pH was not significant on the dissolution rate, and both brands met the compendial requirements.
本研究的目的是研究生理条件对两种商业品牌乙酰水杨酸(ASA)溶出率的影响，并与药典试验进行比较。所有分析参数均按照ICH (Q2(R1))指南选择，并进行统计验证。采用紫外-可见分光光度法测定了ASA在不同pH值(6.8和4.9)下的最大波长(λmax)和吸光度(ε)。以乙醇(EtOH)为助溶剂时，ε为3.15;以0.1 N NaOH为助溶剂时，ε为18.50。溶出度试验按药典规范进行;然而，在药典中缺乏确定ε的直接规范，使得使用不同溶剂的可能性很大。,当使用氢氧化钠溶解ASA,ε计算是18.50,并开展compendial解散测试肠衣平板电脑,只有20%的ASA 4 h后被释放。在分析相同的数据时使用的ε3.15(计算从EtOH溶解ASA),亚撒的释放量2 h后被发现95%。此外,美联储和禁食状态pH值的影响不显著的溶解速度,和两个品牌compendial需求。
{"title":"Impact of Solvent Selection and Absorptivity on Dissolution Testing of Acetylsalicylic Acid Enteric-Coated Tablets","authors":"Samah A. Ata, O. Tarawneh, Rana Sejare, Suhair Sunoqrot, Rania A. Al-Qirim","doi":"10.14227/DT280221P22","DOIUrl":"https://doi.org/10.14227/DT280221P22","url":null,"abstract":"The objective of this study was to investigate the effect of physiological conditions on the dissolution rate of acetylsalicylic acid (ASA) from two commercial brands compared against compendial tests. All parameters of the analysis were chosen according to ICH (Q2(R1)) guidelines and were validated statistically. The maximum wavelength (λmax) and absorptivity (ε) for ASA were determined in different solvents at different pH values (6.8 and 4.9) by a validated UV-Vis spectrophotometric method. When ethanol (EtOH) was used as co-solvent, ε was found to be 3.15, and when 0.1 N NaOH was used, ε was 18.50. Dissolution tests were conducted according to pharmacopeia specifications; however, the lack of a direct specification in determining ε in the pharmacopeia has permitted enormous probabilities of employing different solvents. Herein, when NaOH was used to dissolve ASA, ε was calculated to be 18.50, and upon conducting compendial dissolution tests for enteric-coated tablets, only 20% of ASA was released after 4 h. When analyzing the same data using ε of 3.15 (calculated from dissolving ASA in EtOH), the amount of released ASA was found to be 95% after 2 h. Furthermore, the effect of a fed and fasted state pH was not significant on the dissolution rate, and both brands met the compendial requirements.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"22-29"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Mann, Michael Cohen, Andreas M. Abend, C. Coutant, Lee Ashworth, Robert Shaw, Gavin P Reynolds, I. Nir, V. Shah, S. Shaw, Ashvina Patel, Xujin Lu, Vincent Cicale, Meagan McCallum, Sanj K. Patel, Josey E. Topolski, S. Prüfer, I. Tomaszewska, A. Kourentas, M. Mueller-Zsigmondy, Julian S. Williams, M. Ainge, P. Berben, Anne Bouquelle, B. Abrahamsson, A. Karlsson, Ria Varghese, Fashen Li, Amy Orce, B. Nickerson, Xianjie Shao
Marta I. V. Brevedan, M. A. Varillas, N. L. G. Vidal
Sildenafil citrate is a selective inhibitor of the enzyme phosphodiesterase type 5, used to treat erectile dysfunction in adults and pulmonary hypertension, mainly in children. This work aimed to perform a comparative study of sildenafil tablets marketed in Argentina and establish their pharmaceutical equivalence. Eight commercial formulations (immediate-release tablets) containing 50 mg of sildenafil were analyzed according to United States and Argentinian Pharmacopoeial guidelines. The assay was performed by UV spectrophotometry in 0.01 N hydrochloric acid. Similar conditions were used for dissolution tests, which were carried out in a basket apparatus at 100 rpm. All samples met pharmacopeial specifications for acceptance (i.e., assay, content uniformity, hardness, friability, disintegration, and in vitro dissolution) for immediate-release dosage forms. When compared to the reference formulation, a statistically significant difference was noted for dissolution efficiency in one case (sample F). Based on the obtained results, it is possible to conclude that the evaluated formulations of sildenafil can be considered pharmaceutical equivalents.
{"title":"Comparative Assessment of Critical Quality Attributes of Sildenafil Tablets","authors":"Marta I. V. Brevedan, M. A. Varillas, N. L. G. Vidal","doi":"10.14227/DT280121PGC1","DOIUrl":"https://doi.org/10.14227/DT280121PGC1","url":null,"abstract":"Sildenafil citrate is a selective inhibitor of the enzyme phosphodiesterase type 5, used to treat erectile dysfunction in adults and pulmonary hypertension, mainly in children. This work aimed to perform a comparative study of sildenafil tablets marketed in Argentina and establish their pharmaceutical equivalence. Eight commercial formulations (immediate-release tablets) containing 50 mg of sildenafil were analyzed according to United States and Argentinian Pharmacopoeial guidelines. The assay was performed by UV spectrophotometry in 0.01 N hydrochloric acid. Similar conditions were used for dissolution tests, which were carried out in a basket apparatus at 100 rpm. All samples met pharmacopeial specifications for acceptance (i.e., assay, content uniformity, hardness, friability, disintegration, and in vitro dissolution) for immediate-release dosage forms. When compared to the reference formulation, a statistically significant difference was noted for dissolution efficiency in one case (sample F). Based on the obtained results, it is possible to conclude that the evaluated formulations of sildenafil can be considered pharmaceutical equivalents.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angel T. Alvarado, A. M. Muñoz, M. Bendezu, Jorge A. García, Juan J. Palomino-Jhong, Gaby Ochoa-Pachas, Andres Chonn-Chang, Luis Sullón-Dextre, B. Loja-Herrera, Mario Pineda-Pérez
This research evaluated the biopharmaceutical equivalence in vitro of three brands of glibenclamide 5-mg tablets (reference, brand name, and generic drugs) from Lima, Peru following the guidelines of the Biopharmaceutical Classification System (BCS). Glibenclamide is a BCS class 2 drug. Quality control parameters were evaluated including hardness, weight, friability, and drug content (hardness: 2.6–2.8 kg-f; weight [mean ± SD]: 103.3–109.8 mg ± 0.27–0.53; friability: 0.19–0.55%; content: 100.65–103.3%). To assess dissolution, apparatus 2 was used at 75 rpm, 900 mL of dissolution medium (37 ± 0.5 °C) at pH 6.8; simulated intestinal fluid without enzymes was used as the dissolution medium. Samples (5 mL) were withdrawn at 5, 10, 15, 30, 45, 60, and 90 min and analyzed at 300 nm in a UV spectrophotometer. Dissolution percentages were 52.79–59.78% at 15 minutes, 59.78–64.54% at 30 mins, 79.64–85.13% at 60 min, and 98.33–99.92% at 90 min. Based on the similarity factor (f2), the dissolution profiles of the brand name (66.61) and generic (70.10) drugs were considered similar to the reference drug (i.e., f2 50–100). Dissolution efficiency was greater than 70% and mean dissolution time exceeded 30 min (p > 0.05). According to the similarity factor and dissolution efficiency, the brand name and generic drugs are biopharmaceutical equivalents in vitro with the reference drug at pH 6.8, with a percentage difference < 5%. However, glibenclamide tablets cannot be exempt from relative bioavailability studies because they did not release at least 85% of the drug within 30 minutes.
{"title":"In Vitro Biopharmaceutical Equivalence of 5-mg Glibenclamide Tabletsin Simulated Intestinal Fluid Without Enzymes","authors":"Angel T. Alvarado, A. M. Muñoz, M. Bendezu, Jorge A. García, Juan J. Palomino-Jhong, Gaby Ochoa-Pachas, Andres Chonn-Chang, Luis Sullón-Dextre, B. Loja-Herrera, Mario Pineda-Pérez","doi":"10.14227/DT280121PGC2","DOIUrl":"https://doi.org/10.14227/DT280121PGC2","url":null,"abstract":"This research evaluated the biopharmaceutical equivalence in vitro of three brands of glibenclamide 5-mg tablets (reference, brand name, and generic drugs) from Lima, Peru following the guidelines of the Biopharmaceutical Classification System (BCS). Glibenclamide is a BCS class 2 drug. Quality control parameters were evaluated including hardness, weight, friability, and drug content (hardness: 2.6–2.8 kg-f; weight [mean ± SD]: 103.3–109.8 mg ± 0.27–0.53; friability: 0.19–0.55%; content: 100.65–103.3%). To assess dissolution, apparatus 2 was used at 75 rpm, 900 mL of dissolution medium (37 ± 0.5 °C) at pH 6.8; simulated intestinal fluid without enzymes was used as the dissolution medium. Samples (5 mL) were withdrawn at 5, 10, 15, 30, 45, 60, and 90 min and analyzed at 300 nm in a UV spectrophotometer. Dissolution percentages were 52.79–59.78% at 15 minutes, 59.78–64.54% at 30 mins, 79.64–85.13% at 60 min, and 98.33–99.92% at 90 min. Based on the similarity factor (f2), the dissolution profiles of the brand name (66.61) and generic (70.10) drugs were considered similar to the reference drug (i.e., f2 50–100). Dissolution efficiency was greater than 70% and mean dissolution time exceeded 30 min (p > 0.05). According to the similarity factor and dissolution efficiency, the brand name and generic drugs are biopharmaceutical equivalents in vitro with the reference drug at pH 6.8, with a percentage difference < 5%. However, glibenclamide tablets cannot be exempt from relative bioavailability studies because they did not release at least 85% of the drug within 30 minutes.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Performance Tests – Update on USP Activities","authors":"Margareth R. C. Marques","doi":"10.14227/DT280121P40","DOIUrl":"https://doi.org/10.14227/DT280121P40","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"40-41"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Because drug-surfactant interactions are specific, careful choice of surfactant media is required to develop dissolution tests for Biopharmaceutics Classification System (BCS) Class II drugs. The purpose of this study was to investigate the effects of cationic hexadecyltrimethylammonium bromide (CTAB) and nonionic surfactants (polysorbate 80) on the dissolution of bioequivalent immediate-release formulations of a BCS Class II anticancer drug, tamoxifen citrate (TMX), and to identify the most suitable surfactant medium reflecting the formulation differences and in vivo dissolution of the drug. Dissolution behaviors of the reference and test products were studied using USP apparatus II at pH 1.2, 4.5, and 6.8 with and without surfactant. At pH 6.8, the effects of 0.5% (w/v) CTAB and 0.5% (w/v) polysorbate 80 on dissolution of the formulations were much more pronounced compared to pH 1.2. Based on model-dependent and modelindependent approaches, test products were found to be different from the reference in all surfactant media. Overall, none of the surfactant media reflected the bioequivalence of test products to the reference; however, polysorbate 80 may provide a discriminative test for certain formulation changes, and it may be physiologically meaningful to mimic in vivo solubilization and sink conditions due to continuous intestinal absorption of TMX.
{"title":"Role of Surfactants on Dissolution Behavior of Tamoxifen","authors":"T. Incecayir, Seval Olgac, D. Usta, Z. Teksin","doi":"10.14227/DT280221P6","DOIUrl":"https://doi.org/10.14227/DT280221P6","url":null,"abstract":"Because drug-surfactant interactions are specific, careful choice of surfactant media is required to develop dissolution tests for Biopharmaceutics Classification System (BCS) Class II drugs. The purpose of this study was to investigate the effects of cationic hexadecyltrimethylammonium bromide (CTAB) and nonionic surfactants (polysorbate 80) on the dissolution of bioequivalent immediate-release formulations of a BCS Class II anticancer drug, tamoxifen citrate (TMX), and to identify the most suitable surfactant medium reflecting the formulation differences and in vivo dissolution of the drug. Dissolution behaviors of the reference and test products were studied using USP apparatus II at pH 1.2, 4.5, and 6.8 with and without surfactant. At pH 6.8, the effects of 0.5% (w/v) CTAB and 0.5% (w/v) polysorbate 80 on dissolution of the formulations were much more pronounced compared to pH 1.2. Based on model-dependent and modelindependent approaches, test products were found to be different from the reference in all surfactant media. Overall, none of the surfactant media reflected the bioequivalence of test products to the reference; however, polysorbate 80 may provide a discriminative test for certain formulation changes, and it may be physiologically meaningful to mimic in vivo solubilization and sink conditions due to continuous intestinal absorption of TMX.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"6-15"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This post-marketing study on prednisolone products in Sri Lanka was conducted using BCS-based biowaiver procedures for performing in vitro bioequivalence studies. The market leader product with the highest availability was selected as the comparator in the absence of the innovator product. A validated UV/Visible spectrophotometric method was used to quantify the drug dissolution. Cumulative drug release profiles were determined in dissolution media at pH 1.2, 4.5, and 6.8 using the paddle apparatus. Although the two test products and the comparator met pharmacopoeial requirements for quality, they failed to meet in vitro biowaiver criteria. Acceptability of biowaiver study results depends on the performance of the comparator product. Information on the comparator product's bioequivalence to the innovator product was not available. This study revealed the difficulties in low and middle-income countries (LMICs) when conducting biowaiver studies for regulatory submission and highlights the necessity to have bioequivalence data and excipient information for the comparator product for better decision making. The study supports having an international standard comparator product used by LMICs when manufacturing and registering generic drug products.
{"title":"Biowaiver Study of Selected Solid Oral Prednisolone Products Available in Sri Lanka: Recommendations for Comparator Product Used in Biowaiver Testing","authors":"H. Rathnayake, D. Thambavita, P. Galappatthy","doi":"10.14227/DT280121P34","DOIUrl":"https://doi.org/10.14227/DT280121P34","url":null,"abstract":"This post-marketing study on prednisolone products in Sri Lanka was conducted using BCS-based biowaiver procedures for performing in vitro bioequivalence studies. The market leader product with the highest availability was selected as the comparator in the absence of the innovator product. A validated UV/Visible spectrophotometric method was used to quantify the drug dissolution. Cumulative drug release profiles were determined in dissolution media at pH 1.2, 4.5, and 6.8 using the paddle apparatus. Although the two test products and the comparator met pharmacopoeial requirements for quality, they failed to meet in vitro biowaiver criteria. Acceptability of biowaiver study results depends on the performance of the comparator product. Information on the comparator product's bioequivalence to the innovator product was not available. This study revealed the difficulties in low and middle-income countries (LMICs) when conducting biowaiver studies for regulatory submission and highlights the necessity to have bioequivalence data and excipient information for the comparator product for better decision making. The study supports having an international standard comparator product used by LMICs when manufacturing and registering generic drug products.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"34-39"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoga Windhu Wardhana, Eli Nur Aisyah, I. Sopyan, T. Rusdiana
Efavirenz (EFV) was approved by the United States Food and Drug Administration in 1998 with no polymorphic forms, but further research defined 23 different forms, including amorphous and solvated forms. This study aims to determine the ability of dissolved EFV polymorphs in in vitro media kinetic release models of pKa values. The polymorph types were obtained through various organic solvents such as acetonitrile, n-hexane, and methanol, i.e., form I, II, and III. The characteristics were distinguished by polarisation microscopy, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and Raman spectroscopy. The solubility and dissolution of each polymorph were examined by adding 0.25% sodium lauryl sulphate (SLS) to the comparative dissolution media (water, HCl at pH 1.2, phosphate buffer at pH 4.6 and 6.8). The different microscopic shapes provided a unique fingerprint in the FTIR and the Raman spectra. The thermal behaviour examination provided a DSC thermogram with a specific melting point for each polymorph. The results of the solubility and dissolution tests reported that the highest peak was reached by form II, followed by forms III and I. These followed the pKa values of each polymorph, namely 10.12, 10.63, and 10.37 for form I, II, and III, respectively. The dissolution profile shows that pH conditions affect the release kinetics of form I compared to the metastable forms. The kinetic model of form I is pH-dependent; the acidic medium provided a slower release rate. Unlike the metastable forms, drug loading remained constant but still followed Higuchi’s kinetic release model, even in acidic medium.
{"title":"In Vitro Solubility and Release Profile Correlation with pKa Value of Efavirenz Polymorphs","authors":"Yoga Windhu Wardhana, Eli Nur Aisyah, I. Sopyan, T. Rusdiana","doi":"10.14227/dt280321p14","DOIUrl":"https://doi.org/10.14227/dt280321p14","url":null,"abstract":"Efavirenz (EFV) was approved by the United States Food and Drug Administration in 1998 with no polymorphic forms, but further research defined 23 different forms, including amorphous and solvated forms. This study aims to determine the ability of dissolved EFV polymorphs in in vitro media kinetic release models of pKa values. The polymorph types were obtained through various organic solvents such as acetonitrile, n-hexane, and methanol, i.e., form I, II, and III. The characteristics were distinguished by polarisation microscopy, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and Raman spectroscopy. The solubility and dissolution of each polymorph were examined by adding 0.25% sodium lauryl sulphate (SLS) to the comparative dissolution media (water, HCl at pH 1.2, phosphate buffer at pH 4.6 and 6.8). The different microscopic shapes provided a unique fingerprint in the FTIR and the Raman spectra. The thermal behaviour examination provided a DSC thermogram with a specific melting point for each polymorph. The results of the solubility and dissolution tests reported that the highest peak was reached by form II, followed by forms III and I. These followed the pKa values of each polymorph, namely 10.12, 10.63, and 10.37 for form I, II, and III, respectively. The dissolution profile shows that pH conditions affect the release kinetics of form I compared to the metastable forms. The kinetic model of form I is pH-dependent; the acidic medium provided a slower release rate. Unlike the metastable forms, drug loading remained constant but still followed Higuchi’s kinetic release model, even in acidic medium.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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