J. Njoku, Dwaipayan Mukherjee, G. K. Webster, R. Löbenberg
Excipients play an important role in the formulation of dosage forms and can be used to improve the bioavailability of a drug through physical interactions that alter the rate of dissolution of a drug. The objective of this study was to predict the effect of formulation on the dissolution rate of a poorly soluble drug using computer simulations. Solid dispersion of ritonavir was prepared. Dissolution test results of direct compressed tablets with and without disintegrant in various media with physiologically relevant pH were compared with simulations. Solubilizer and disintegrant effect were evaluated on the Dose, Disintegration, and Dissolution Plus (DDDPlus) simulation software (version 5.0.0011, Simulations Plus, Inc., Lancaster, CA, USA) using previously published solubility data on ritonavir. Observed and predicted dissolution profiles similarity tests and drug release mechanisms were assessed. Optimization of the solubilizer effect coefficient (SEC) on the program gives good estimations of the effect of copovidone in the solid dispersion in the dissolution profiles of all tablets. The SEC is dependent on the solubility of the active pharmaceutical ingredient (API) at the local pH and the dissolved concentration of the solubilizer. Disintegrant concentration in the program has no effect on simulations, rather the disintegration time was the predictive factor. Drug release was formulation controlled in the tablets without disintegrant and in the tablets with disintegrant was via drug diffusion and polymer surface erosion. DDDPlus has the potential to estimate the effect of excipients in a formulation on in vitro dissolution at an early stage in the drug development process. This could be useful in decisions on formulation strategies to enhance bioavailability in poorly soluble drugs.
赋形剂在剂型的配制中起着重要的作用，可以通过改变药物溶出速率的物理相互作用来提高药物的生物利用度。本研究的目的是利用计算机模拟预测配方对难溶性药物溶出率的影响。制备了利托那韦的固体分散体。用模拟方法比较了含崩解剂和不含崩解剂的直接压片在不同pH值与生理相关的介质中的溶出度试验结果。使用先前发表的利托那韦溶解度数据，在Dose，崩解和溶解Plus (DDDPlus)模拟软件(版本5.0.0011,Simulations Plus, Inc.， Lancaster, CA, USA)上评估增溶剂和崩解剂的效果。观察和预测溶出谱相似试验和药物释放机制进行评估。优化增溶剂效应系数(SEC)对程序的影响，可以较好地估计copovidone在所有片剂溶出曲线中的固体分散效果。SEC取决于活性药物成分(API)在当地pH值下的溶解度和增溶剂的溶解浓度。程序中崩解剂浓度对模拟结果没有影响，崩解时间是预测因素。不含崩解剂的片剂通过处方控制药物释放，含崩解剂的片剂通过药物扩散和聚合物表面侵蚀控制药物释放。DDDPlus有可能在药物开发过程的早期阶段估计制剂中辅料对体外溶出度的影响。这可能有助于制定配方策略，以提高难溶性药物的生物利用度。
{"title":"Amorphous Solid Dispersions in Early Stage of Formulation Development: Predicting Excipient Influence on Dissolution Profiles Using DDDPlus","authors":"J. Njoku, Dwaipayan Mukherjee, G. K. Webster, R. Löbenberg","doi":"10.14227/dt270220p6","DOIUrl":"https://doi.org/10.14227/dt270220p6","url":null,"abstract":"Excipients play an important role in the formulation of dosage forms and can be used to improve the bioavailability of a drug through physical interactions that alter the rate of dissolution of a drug. The objective of this study was to predict the effect of formulation on the dissolution rate of a poorly soluble drug using computer simulations. Solid dispersion of ritonavir was prepared. Dissolution test results of direct compressed tablets with and without disintegrant in various media with physiologically relevant pH were compared with simulations. Solubilizer and disintegrant effect were evaluated on the Dose, Disintegration, and Dissolution Plus (DDDPlus) simulation software (version 5.0.0011, Simulations Plus, Inc., Lancaster, CA, USA) using previously published solubility data on ritonavir. Observed and predicted dissolution profiles similarity tests and drug release mechanisms were assessed. Optimization of the solubilizer effect coefficient (SEC) on the program gives good estimations of the effect of copovidone in the solid dispersion in the dissolution profiles of all tablets. The SEC is dependent on the solubility of the active pharmaceutical ingredient (API) at the local pH and the dissolved concentration of the solubilizer. Disintegrant concentration in the program has no effect on simulations, rather the disintegration time was the predictive factor. Drug release was formulation controlled in the tablets without disintegrant and in the tablets with disintegrant was via drug diffusion and polymer surface erosion. DDDPlus has the potential to estimate the effect of excipients in a formulation on in vitro dissolution at an early stage in the drug development process. This could be useful in decisions on formulation strategies to enhance bioavailability in poorly soluble drugs.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"6-13"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813007","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}
G. K. Webster, Xi Shao, K. Nelson, Matthew A. Gragg
Cleaning in any Good Manufacturing Practice (GMP) laboratory is an important aspect of the analytical experiment. The laboratory must ensure the equipment does not contain residual active pharmaceutical ingredients (APIs) or impurities that may affect the outcome of any current or future experiments. While this is standard practice for GMP manufacturing operations, common laboratory equipment is often held to less stringent standards. The potential manhours lost due to investigations for extraneous peaks and contamination can be significant and cause delays in releasing product. Potential compliance issues related to ineffective cleaning are particularly important for dissolution instrumentation. Our laboratory has modeled the challenges of cleaning automated dissolution systems using representative soluble and poorly soluble APIs. Poorly soluble drugs often entail the use of surfactants in the dissolution media which also have a potential carryover issue. Using a manufacturing cleaning validation based approach, the study discussion presented will address the cleaning effectiveness for both sample and media considerations.
{"title":"A Look at Cleaning Effectiveness in Automated Dissolution Systems","authors":"G. K. Webster, Xi Shao, K. Nelson, Matthew A. Gragg","doi":"10.14227/dt270220p14","DOIUrl":"https://doi.org/10.14227/dt270220p14","url":null,"abstract":"Cleaning in any Good Manufacturing Practice (GMP) laboratory is an important aspect of the analytical experiment. The laboratory must ensure the equipment does not contain residual active pharmaceutical ingredients (APIs) or impurities that may affect the outcome of any current or future experiments. While this is standard practice for GMP manufacturing operations, common laboratory equipment is often held to less stringent standards. The potential manhours lost due to investigations for extraneous peaks and contamination can be significant and cause delays in releasing product. Potential compliance issues related to ineffective cleaning are particularly important for dissolution instrumentation. Our laboratory has modeled the challenges of cleaning automated dissolution systems using representative soluble and poorly soluble APIs. Poorly soluble drugs often entail the use of surfactants in the dissolution media which also have a potential carryover issue. Using a manufacturing cleaning validation based approach, the study discussion presented will address the cleaning effectiveness for both sample and media considerations.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"14-20"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812179","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}
The purpose of this research was to evaluate the release pattern of the dual-release pellets of diclofenac sodium (DS), coated with entericand sustained-release layers, in dissolution media that resemble the physiological variables of the gastrointestinal (GI) fluid. Dissolution testing in three pH stages (acidic, intermediate, and basic) was conducted using USP apparatus I (basket) rotating at 100 rpm. The acidic pH stage resembles the gastric fluid during fasted and fed states, the intermediate pH stage resembles the fluid of the proximal small intestine (duodenal fluid), and the basic pH stage resembles the fluid of the small intestine during fasted and fed states and distal GI. DS pellets showed excellent gastric resistance in the acidic pH stage for 2 h. In the intermediate pH stage, DS pellets showed a gastric resistance for 2 h, followed by a low percent of DS release thereafter (15.2% after 10 h). DS release was accelerated in the basic pH stage, particularly in pH media 6.5–7.2. This is because the enteric-coated film starts to dissolve at pH > 5.5. In addition, DS release was influenced by the buffer capacity (β)/ionic strength (I) of the dissolution media, where DS release increased with increasing β/I of phosphate buffers (pH 6.8) up to a concentration of 50 mM and then decreased at 100 mM. These dissolution results corroborated with equilibrium solubility data and sink conditions (S values) of DS in the media of the three pH stages. This study provides an insight into the release pattern of the dual-release DS pellets throughout the GI tract to better correlate the in vitro release data of these pellets to those in vivo.
{"title":"Drug Release Pattern of Oral Dual-Release Pellets Through the Gastrointestinal Tract: Case Example of Diclofenac Sodium","authors":"R. Hamed, S. Alnadi","doi":"10.14227/dt270220p22","DOIUrl":"https://doi.org/10.14227/dt270220p22","url":null,"abstract":"The purpose of this research was to evaluate the release pattern of the dual-release pellets of diclofenac sodium (DS), coated with entericand sustained-release layers, in dissolution media that resemble the physiological variables of the gastrointestinal (GI) fluid. Dissolution testing in three pH stages (acidic, intermediate, and basic) was conducted using USP apparatus I (basket) rotating at 100 rpm. The acidic pH stage resembles the gastric fluid during fasted and fed states, the intermediate pH stage resembles the fluid of the proximal small intestine (duodenal fluid), and the basic pH stage resembles the fluid of the small intestine during fasted and fed states and distal GI. DS pellets showed excellent gastric resistance in the acidic pH stage for 2 h. In the intermediate pH stage, DS pellets showed a gastric resistance for 2 h, followed by a low percent of DS release thereafter (15.2% after 10 h). DS release was accelerated in the basic pH stage, particularly in pH media 6.5–7.2. This is because the enteric-coated film starts to dissolve at pH > 5.5. In addition, DS release was influenced by the buffer capacity (β)/ionic strength (I) of the dissolution media, where DS release increased with increasing β/I of phosphate buffers (pH 6.8) up to a concentration of 50 mM and then decreased at 100 mM. These dissolution results corroborated with equilibrium solubility data and sink conditions (S values) of DS in the media of the three pH stages. This study provides an insight into the release pattern of the dual-release DS pellets throughout the GI tract to better correlate the in vitro release data of these pellets to those in vivo.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"22-30"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812190","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":"Questions and Answers August 2020","authors":"Margareth R. C. Marques, M. Liddell","doi":"10.14227/dt270320p44","DOIUrl":"https://doi.org/10.14227/dt270320p44","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"44-45"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812637","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}
Gordana Švonja Parezanović, M. Lalic-Popovic, S. Goločorbin-Kon, N. Todorović, N. Pavlović, M. Mikov
This study aimed to compare the different physical parameters and dissolution profiles of 10 years-expired with nonexpired lamotrigine (LTG) immediate-release tablet formulations. Dissolution tests were conducted using a validated high-performance liquid chromatography method. Dissolution characteristics of the tablet formulations were evaluated at three points spanning the physiological pH range (pH 1.2, pH 4.5, pH 6.8). Physical characteristics of LTG tablets were determined according to the European Pharmacopoeia. The dissolution profile comparison was carried out using model-independent (statistical) and model-dependent (kinetic) methods to provide detailed information about dissolution data. The t-test was applied to investigate differences between expired and non-expired tablets, and the differences were considered statistically significant if p ≤ 0.05. The results demonstrated no statistical differences in physical characteristics between expired and non-expired tablets; however, there were differences in the dissolution profiles, which could cause different pharmacokinetic profiles. The results of this investigation showed that the drug content did not change significantly. Therefore, the lower dissolution rate for expired LTG tablets is due to an interaction of LTG with one or more excipients in the tablet formulation during aging.
{"title":"In Vitro Comparative Quality Evaluation of Non-Expired and 10 Years-Expired Lamotrigine Immediate-Release Tablet Formulations - Pilot Study","authors":"Gordana Švonja Parezanović, M. Lalic-Popovic, S. Goločorbin-Kon, N. Todorović, N. Pavlović, M. Mikov","doi":"10.14227/dt270120p14","DOIUrl":"https://doi.org/10.14227/dt270120p14","url":null,"abstract":"This study aimed to compare the different physical parameters and dissolution profiles of 10 years-expired with nonexpired lamotrigine (LTG) immediate-release tablet formulations. Dissolution tests were conducted using a validated high-performance liquid chromatography method. Dissolution characteristics of the tablet formulations were evaluated at three points spanning the physiological pH range (pH 1.2, pH 4.5, pH 6.8). Physical characteristics of LTG tablets were determined according to the European Pharmacopoeia. The dissolution profile comparison was carried out using model-independent (statistical) and model-dependent (kinetic) methods to provide detailed information about dissolution data. The t-test was applied to investigate differences between expired and non-expired tablets, and the differences were considered statistically significant if p ≤ 0.05. The results demonstrated no statistical differences in physical characteristics between expired and non-expired tablets; however, there were differences in the dissolution profiles, which could cause different pharmacokinetic profiles. The results of this investigation showed that the drug content did not change significantly. Therefore, the lower dissolution rate for expired LTG tablets is due to an interaction of LTG with one or more excipients in the tablet formulation during aging.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"14-20"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812437","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}
João Luís Silva Oliveira, Gilmar Antônio de Carvalho Teles Júnior, Desirée A. Bonfim, Carlos Magno Ramos Carvalho Júnior, Jéssica A. Santos, M. S. Ferreira, A. Júnior
Tetracyclines are widely used for the treatment of infections of the lower respiratory tract and other systems. In Brazil, tetracyclines are available as generic and similar products. The aim of this study was to evaluate the in vitro release of tetracycline capsules (500 mg) and doxycycline tablets (100 mg) in different reaction media, from dissolution profiles, using sensitive and rapid ultraviolet spectrophotometric methods. The dissolution test was used to obtain and compare dissolution profiles and establish similarities of pharmaceutical formulations in compliance with the Brazilian (for tetracycline hydrochloride capsules) and United States (USP) (for doxycycline hydrochloride tablets) pharmacopoeia. For both drugs, the dissolution studies were conducted using an USP type 2 apparatus at 75 rpm with 1000 mL distilled water at 37.0 ± 0.5 oC for 90 minutes, to evaluate the influence of pH (1.0–8.0) on the release of drugs. The methods were validated, showing precision, linearity, and accuracy. All the products satisfactorily released tetracycline and doxycycline, with at least 80% of the drug dissolved within 30 minutes. Tetracycline and doxycycline are weak acids, which favors their dissolution in acid media (pH range 1.0–6.0). This research contributes to studies that guarantee the quality control of tetracyclines and to the expansion of the novel methodologies established by the Brazilian Pharmacopoeia for doxycycline.
{"title":"Effect of Medium pH on In Vitro Dissolution of Marketed Tetracyclines (Tetracycline and Doxycycline) Solid Oral Dosage Forms in Bahia, Brazil","authors":"João Luís Silva Oliveira, Gilmar Antônio de Carvalho Teles Júnior, Desirée A. Bonfim, Carlos Magno Ramos Carvalho Júnior, Jéssica A. Santos, M. S. Ferreira, A. Júnior","doi":"10.14227/dt270220p32","DOIUrl":"https://doi.org/10.14227/dt270220p32","url":null,"abstract":"Tetracyclines are widely used for the treatment of infections of the lower respiratory tract and other systems. In Brazil, tetracyclines are available as generic and similar products. The aim of this study was to evaluate the in vitro release of tetracycline capsules (500 mg) and doxycycline tablets (100 mg) in different reaction media, from dissolution profiles, using sensitive and rapid ultraviolet spectrophotometric methods. The dissolution test was used to obtain and compare dissolution profiles and establish similarities of pharmaceutical formulations in compliance with the Brazilian (for tetracycline hydrochloride capsules) and United States (USP) (for doxycycline hydrochloride tablets) pharmacopoeia. For both drugs, the dissolution studies were conducted using an USP type 2 apparatus at 75 rpm with 1000 mL distilled water at 37.0 ± 0.5 oC for 90 minutes, to evaluate the influence of pH (1.0–8.0) on the release of drugs. The methods were validated, showing precision, linearity, and accuracy. All the products satisfactorily released tetracycline and doxycycline, with at least 80% of the drug dissolved within 30 minutes. Tetracycline and doxycycline are weak acids, which favors their dissolution in acid media (pH range 1.0–6.0). This research contributes to studies that guarantee the quality control of tetracyclines and to the expansion of the novel methodologies established by the Brazilian Pharmacopoeia for doxycycline.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"32-40"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812935","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}
Shahnaz Usman, A. Saeed, Sakina Fatima, V. Ramesh, F. Shah, Quamrul Islam
Introduction: We aimed to study the dissolution behavior of available brands of pregabalin in the United Arab Emirates (UAE) (Ras Al Khaimah) market and to report efficiency and fungibility data for generic brands under biowaiver conditions. Methods: The pharmaceutical parameters of five brands of pregabalin 150 mg capsules were analyzed, including the reference product and four generic products. Dissolution tests were performed as per WHO and FDA recommendations (pH 1.2, 4.5, and 6.8). United States Pharmacopeia (USP) apparatus 2 (paddle, 50 rpm) was used to assess drug release. Multiple time points were measured to estimate the drug release profile of the capsules. Pharmacokinetic models and similarity factor analysis were performed. Results: The percentage of drug release within 15 minutes was 95–102% at pH 1.2, 86–95% at pH 4.5, and 89–98% at pH 6.8. Different kinetic models were used to analyze the suitability level of drug release from the different capsules. In all the three buffers, first order kinetics and the Korsmeyer–Peppas model demonstrated the drug release with R2 ≥ 0.95, which helps to predict and evaluate the acceptability level of drug release. The similarity and difference factor results were within the acceptable range for all capsules. Conclusion: The dissolution profiles of all tested capsules of pregabalin in the UAE market are pharmaceutically and therapeutically equivalent. The results indicate that the post-market analysis is essential for determining interchangeability of different brands of the same drug.
{"title":"In Vitro Bioequivalence of Pregabalin Capsules (150 mg): An Alternative to In Vivo Bioequivalence Studies","authors":"Shahnaz Usman, A. Saeed, Sakina Fatima, V. Ramesh, F. Shah, Quamrul Islam","doi":"10.14227/dt270420p24","DOIUrl":"https://doi.org/10.14227/dt270420p24","url":null,"abstract":"Introduction: We aimed to study the dissolution behavior of available brands of pregabalin in the United Arab Emirates (UAE) (Ras Al Khaimah) market and to report efficiency and fungibility data for generic brands under biowaiver conditions. Methods: The pharmaceutical parameters of five brands of pregabalin 150 mg capsules were analyzed, including the reference product and four generic products. Dissolution tests were performed as per WHO and FDA recommendations (pH 1.2, 4.5, and 6.8). United States Pharmacopeia (USP) apparatus 2 (paddle, 50 rpm) was used to assess drug release. Multiple time points were measured to estimate the drug release profile of the capsules. Pharmacokinetic models and similarity factor analysis were performed. Results: The percentage of drug release within 15 minutes was 95–102% at pH 1.2, 86–95% at pH 4.5, and 89–98% at pH 6.8. Different kinetic models were used to analyze the suitability level of drug release from the different capsules. In all the three buffers, first order kinetics and the Korsmeyer–Peppas model demonstrated the drug release with R2 ≥ 0.95, which helps to predict and evaluate the acceptability level of drug release. The similarity and difference factor results were within the acceptable range for all capsules. Conclusion: The dissolution profiles of all tested capsules of pregabalin in the UAE market are pharmaceutically and therapeutically equivalent. The results indicate that the post-market analysis is essential for determining interchangeability of different brands of the same drug.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"24-31"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812706","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}
M. Waqas, R. Ali, M. Usman, Muhammad Shahid, A. Rasul, B. Khan, G. Murtaza
Dissolution test results are the principal indicator in estimating the in-vivo bioavailability of most oral solid dosage forms and are an important quality attribute to assess the generic formulation. This study was designed to assess the release of co-amoxiclav from finished pharmaceutical solid dosage formulations. Both innovator and generic tablets of co-amoxiclav were subjected to dissolution testing (USP method 2 and HPLC). The innovator’s product (product A) met compendial criteria regarding bioavailability of both amoxicillin and clavulanic acid. The two generic brands, product B and C, failed to meet the criteria for release of amoxicillin (i.e., 80–85%); however, they did achieve 100% release of clavulanic acid in the initial half hour. Moreover, analysis showed significant variance between the innovator’s and generic brands (p < 0.05 for both of amoxicillin products). Hence, the innovator’s and generic brands are not bioequivalent for amoxicillin release, despite both compliance with limits for clavulanic acid release. Failure to achieve dissolution standards argues that compliance with compendial guidelines is critical for generic manufacturing of co-amoxiclav.
{"title":"In Vitro Comparative Dissolution Assessment of Different Brands of Co-Amoxiclav Tablets in Pakistan","authors":"M. Waqas, R. Ali, M. Usman, Muhammad Shahid, A. Rasul, B. Khan, G. Murtaza","doi":"10.14227/dt270420pgc1","DOIUrl":"https://doi.org/10.14227/dt270420pgc1","url":null,"abstract":"Dissolution test results are the principal indicator in estimating the in-vivo bioavailability of most oral solid dosage forms and are an important quality attribute to assess the generic formulation. This study was designed to assess the release of co-amoxiclav from finished pharmaceutical solid dosage formulations. Both innovator and generic tablets of co-amoxiclav were subjected to dissolution testing (USP method 2 and HPLC). The innovator’s product (product A) met compendial criteria regarding bioavailability of both amoxicillin and clavulanic acid. The two generic brands, product B and C, failed to meet the criteria for release of amoxicillin (i.e., 80–85%); however, they did achieve 100% release of clavulanic acid in the initial half hour. Moreover, analysis showed significant variance between the innovator’s and generic brands (p < 0.05 for both of amoxicillin products). Hence, the innovator’s and generic brands are not bioequivalent for amoxicillin release, despite both compliance with limits for clavulanic acid release. Failure to achieve dissolution standards argues that compliance with compendial guidelines is critical for generic manufacturing of co-amoxiclav.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812793","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":"Questions and Answers November 2020","authors":"Margareth R. C. Marques, M. Liddell","doi":"10.14227/dt270420p42","DOIUrl":"https://doi.org/10.14227/dt270420p42","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812757","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}
Josyane Márcia Vasconcelos Alves, Livia D. Prado, H. Rocha
Carvedilol is an antihypertensive agent with blocking non-selective (selectivity for β1 and β2 adrenoceptors is moderate) with vasodilating properties conferred on the α-receptor blockade. The molecular structure has one chiral center, so the drug exists as two enantiomers. Furthermore, it presents different polymorphs depending on the synthetic route that is used to obtain the drug. Carvedilol is a weak base, practically insoluble in water, acidic solutions, and gastric and intestinal fluids, and is classified as Class II (Biopharmaceutical Classification System). It presents different solubilities in accordance with the pH of the solvent. In a previous report, it was demonstrated that batches provided by different manufacturers could have different physicochemical properties. The objective of the present study is to evaluate these properties in the formulation of the final tablets and evaluate the best dissolution method. Different media were used to evaluate the impact of raw material characteristics on in vitro release of drug from tablets containing 12.5 mg carvedilol. Pilot batches were obtained by direct compression and wet granulation. Dissolution profiles were compared with a reference drug. Formulations evaluated by wet granulation using carvedilol with a specific particle size (d10 ~ 10 μm and d90 ~ 95 μm) had similar dissolution profiles to the reference product according to United States Pharmacopeia test 2 and fasted-state simulated intestinal fluid (FaSSIF). The results showed the composition of dissolution medium has a direct impact on the dissolution profile of carvedilol.
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