Y. Upadhyay, Ashutosh Kumar Singh, Sanjeev Mishra, S. Gurule, A. Khuroo, Soumya Verma, Neeta Tiwari, S. Bedi
Excipients play a very important role in the release pattern of an active pharmaceutical ingredient from topical semisolid dosages forms, and their physical and chemical properties can influence the release. The aim of this paper was to provide a validated, sensitive, and reproducible method to assess the in vitro release rate of an antifungal drug (Terbinafine) from controlled drug delivery systems (cutaneous and film-forming solution) and to prove product sameness. The samples obtained from in vitro testing were analyzed through a high performance liquid chromatographic (HPLC) system coupled with UV spectrometer at a wavelength of 283 nm. A Franz diffusion cell (FDC) system was used for the dissolution test. We recorded the drug release from the formulation for 6 hours. The release rate obtained from cutaneous and filmforming solutions were compared statistically to depict the sameness. The results met the relevant acceptance criteria (i.e., 90% confidence interval, falling within the limits of 75–133%) as defined in the scale-up and post-approval changes (SUPAC-SS) guidance. The obtained results confirm the competence of the IVRT method for the assessment of product sameness.
{"title":"Comparison of Release Rates Derived from Cutaneous Versus Film-Forming Solution Containing Terbinafine: Approach Towards Qualification and Validation of In Vitro Parameters","authors":"Y. Upadhyay, Ashutosh Kumar Singh, Sanjeev Mishra, S. Gurule, A. Khuroo, Soumya Verma, Neeta Tiwari, S. Bedi","doi":"10.14227/dt290122p28","DOIUrl":"https://doi.org/10.14227/dt290122p28","url":null,"abstract":"Excipients play a very important role in the release pattern of an active pharmaceutical ingredient from topical semisolid dosages forms, and their physical and chemical properties can influence the release. The aim of this paper was to provide a validated, sensitive, and reproducible method to assess the in vitro release rate of an antifungal drug (Terbinafine) from controlled drug delivery systems (cutaneous and film-forming solution) and to prove product sameness. The samples obtained from in vitro testing were analyzed through a high performance liquid chromatographic (HPLC) system coupled with UV spectrometer at a wavelength of 283 nm. A Franz diffusion cell (FDC) system was used for the dissolution test. We recorded the drug release from the formulation for 6 hours. The release rate obtained from cutaneous and filmforming solutions were compared statistically to depict the sameness. The results met the relevant acceptance criteria (i.e., 90% confidence interval, falling within the limits of 75–133%) as defined in the scale-up and post-approval changes (SUPAC-SS) guidance. The obtained results confirm the competence of the IVRT method for the assessment of product sameness.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813144","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}
W. Ahsan, Md. Shamsher Alam, S. Javed, H. Alhazmi, M. Albratty, A. Najmi, M. Sultan
Rosuvastatin (RST), a BCS class II drug, is a poorly water-soluble antihyperlipidemic agent. The aim of the present work was to determine and compare the drug release kinetics from the RST calcium innovator (Crestor) and generic products (Ivarin and Resova) marketed in Saudi Arabia by employing various drug release kinetic mathematical models. A dissolution study was performed on all RST calcium immediate-release tablets. The in vitro drug release profiles were determined in three different dissolution media: 0.1 N HCl (pH 1.2), 0.05 M phosphate buffer (pH 6.8), and 0.05 M citrate buffer (pH 6.6). Drug release data were obtained, correlated quantitatively, and interpreted with the help of mathematical models, then the drug release kinetics were analyzed. The criterion for selecting the most suitable model was based on the highest coefficient of correlation ( R 2 ) with the dissolution profile in each respective media. The innovator product followed the Hixson-Crowell model ( R 2 = 0.955) only in 0.1 N HCl (pH 1.2), whereas in other media all the formulations followed first order release kinetics with non-swellable matrix Fickian diffusion, which is considered ideal for an immediate-release tablet formulation.
瑞舒伐他汀(RST)， BCS II类药物，是一种低水溶性抗高脂血症药物。本研究的目的是通过采用各种药物释放动力学数学模型，确定和比较在沙特阿拉伯销售的RST钙创新产品(Crestor)和仿制产品(Ivarin和Resova)的药物释放动力学。对所有RST钙速释片进行溶出度研究。在0.1 N HCl (pH 1.2)、0.05 M磷酸盐缓冲液(pH 6.8)和0.05 M柠檬酸缓冲液(pH 6.6)三种不同的溶出介质中测定体外药物释放谱。获得药物释放数据，定量关联，并用数学模型进行解释，分析药物释放动力学。选择最合适的模型的标准是根据最高的相关系数(r2)与各介质中的溶出曲线。创新产品仅在0.1 N HCl (pH 1.2)中符合Hixson-Crowell模型(r2 = 0.955)，而在其他介质中，所有配方均遵循一级释放动力学，即不可膨胀的基质菲克扩散，被认为是理想的速释片配方。
{"title":"Study of Drug Release Kinetics of Rosuvastatin Calcium Immediate-Release Tablets Marketed in Saudi Arabia","authors":"W. Ahsan, Md. Shamsher Alam, S. Javed, H. Alhazmi, M. Albratty, A. Najmi, M. Sultan","doi":"10.14227/dt290222pgc1","DOIUrl":"https://doi.org/10.14227/dt290222pgc1","url":null,"abstract":"Rosuvastatin (RST), a BCS class II drug, is a poorly water-soluble antihyperlipidemic agent. The aim of the present work was to determine and compare the drug release kinetics from the RST calcium innovator (Crestor) and generic products (Ivarin and Resova) marketed in Saudi Arabia by employing various drug release kinetic mathematical models. A dissolution study was performed on all RST calcium immediate-release tablets. The in vitro drug release profiles were determined in three different dissolution media: 0.1 N HCl (pH 1.2), 0.05 M phosphate buffer (pH 6.8), and 0.05 M citrate buffer (pH 6.6). Drug release data were obtained, correlated quantitatively, and interpreted with the help of mathematical models, then the drug release kinetics were analyzed. The criterion for selecting the most suitable model was based on the highest coefficient of correlation ( R 2 ) with the dissolution profile in each respective media. The innovator product followed the Hixson-Crowell model ( R 2 = 0.955) only in 0.1 N HCl (pH 1.2), whereas in other media all the formulations followed first order release kinetics with non-swellable matrix Fickian diffusion, which is considered ideal for an immediate-release tablet formulation.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813351","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 aim of this study was to formulate and evaluate bisoprolol hemifumarate emulgel using carbopol 934P with the enhancers, thymus oil and olive oil. Thymus oil and olive oil were used as permeation enhancers. The emulsion formulations were added to a base gel. The emulgel was characterized for physical characteristics, stability, skin irritation, and drug release. Formulations F1 and F5 indicated the best in-vitro drug release when compared with other preparations. Bisoprolol hemifumarate emulgel containing carbopol 934P and thymus oil or olive oil enhancers could be further developed for a topical drug delivery system.
{"title":"Formulation and Evaluation of Bisoprolol Hemifumarate Emulgel for Transdermal Drug Delivery","authors":"R. Gul, Y. Khan, Tajala Aman","doi":"10.14227/dt290522p38","DOIUrl":"https://doi.org/10.14227/dt290522p38","url":null,"abstract":"The aim of this study was to formulate and evaluate bisoprolol hemifumarate emulgel using carbopol 934P with the enhancers, thymus oil and olive oil. Thymus oil and olive oil were used as permeation enhancers. The emulsion formulations were added to a base gel. The emulgel was characterized for physical characteristics, stability, skin irritation, and drug release. Formulations F1 and F5 indicated the best in-vitro drug release when compared with other preparations. Bisoprolol hemifumarate emulgel containing carbopol 934P and thymus oil or olive oil enhancers could be further developed for a topical drug delivery system.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"05 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813919","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}
Daniela Amaral Silva, N. Davies, N. Bou-Chacra, H. Ferraz, R. Löbenberg
Dissolution testing constitutes one of the most widely used in vitro performance tests during drug development and routine quality control testing. It monitors the rate and extent of in vitro drug release (batch release test), and it is often used to ensure consistent in vivo performance. The purpose of this review is to summarize and update the many physiologically adapted media and buffers proposed over the years, focusing on the upper gastrointestinal tract because this is where most drug absorption occurs. Emphasis will be given on the application of bicarbonate-based media because this is the major buffering species in the human intestinal lumen. Due to the pragmatical difficulties of using bicarbonate-based dissolution media, surrogate media with simpler buffer systems are desirable. Herein we describe some of the proposed models and different approaches to develop such substitutes. Special consideration has to be taken when dealing with enteric coated (delayed release) formulations because the interaction of coating polymer with bicarbonate is very complex. All factors considered, using physiologically relevant conditions can ameliorate the risks and enable drug development with increased likelihood to select formulations with the desired in vivo performance.
{"title":"Update on Gastrointestinal Biorelevant Media and Physiologically Relevant Dissolution Conditions","authors":"Daniela Amaral Silva, N. Davies, N. Bou-Chacra, H. Ferraz, R. Löbenberg","doi":"10.14227/dt290222p62","DOIUrl":"https://doi.org/10.14227/dt290222p62","url":null,"abstract":"Dissolution testing constitutes one of the most widely used in vitro performance tests during drug development and routine quality control testing. It monitors the rate and extent of in vitro drug release (batch release test), and it is often used to ensure consistent in vivo performance. The purpose of this review is to summarize and update the many physiologically adapted media and buffers proposed over the years, focusing on the upper gastrointestinal tract because this is where most drug absorption occurs. Emphasis will be given on the application of bicarbonate-based media because this is the major buffering species in the human intestinal lumen. Due to the pragmatical difficulties of using bicarbonate-based dissolution media, surrogate media with simpler buffer systems are desirable. Herein we describe some of the proposed models and different approaches to develop such substitutes. Special consideration has to be taken when dealing with enteric coated (delayed release) formulations because the interaction of coating polymer with bicarbonate is very complex. All factors considered, using physiologically relevant conditions can ameliorate the risks and enable drug development with increased likelihood to select formulations with the desired in vivo performance.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813252","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}
Liqui-Pellet formulations have been introduced as a technology to improve the dissolution rate of poorly water-soluble drugs. This study aimed to incorporate sodium bicarbonate (NaHCO 3 ) into the Liqui-Pellet formulation to explore the potential impact on the drug release rate. Naproxen Liqui-Pellet formulations containing 5%, 12%, 22%, 32%, and 42% w/w of NaHCO 3 were successfully produced and their physicochemical properties were investigated and compared with a physical mixture pellet formulation. Incorporation of such a large amount of functional excipient is impossible or near impossible in the classical liquisolid formulation due to weight and size limitations, particularly for high-dose drugs. The results showed that NaHCO 3 is an effective functional excipient to enhance the drug dissolution rate. The Liqui-Pellet formulation with 42% w/w NaHCO 3 released 76.4% of drug after 2 hours at pH 1.2, which was 14 times faster than the physical mixture pellet (5.5% drug release in 2 h). In general, a faster dissolution rate was observed with increasing NaHCO 3 concentration; however, there was a limit to this effect. Above a certain limit, the influence of NaHCO 3 on the dissolution rate lessened. The flowability test showed that all formulations have good to excellent flowability. Overall, this study demonstrates the flexibility of Liqui-Pellets in terms of formulation design, which in turn further supports the potential of Liqui-Pellets as the next generation oral dosage form.
{"title":"A Novel Application of an Effervescent Agent in Naproxen Liqui-Pellets for Enhanced Drug Release","authors":"Matthew Lam, A. Nokhodchi","doi":"10.14227/dt290222p94","DOIUrl":"https://doi.org/10.14227/dt290222p94","url":null,"abstract":"Liqui-Pellet formulations have been introduced as a technology to improve the dissolution rate of poorly water-soluble drugs. This study aimed to incorporate sodium bicarbonate (NaHCO 3 ) into the Liqui-Pellet formulation to explore the potential impact on the drug release rate. Naproxen Liqui-Pellet formulations containing 5%, 12%, 22%, 32%, and 42% w/w of NaHCO 3 were successfully produced and their physicochemical properties were investigated and compared with a physical mixture pellet formulation. Incorporation of such a large amount of functional excipient is impossible or near impossible in the classical liquisolid formulation due to weight and size limitations, particularly for high-dose drugs. The results showed that NaHCO 3 is an effective functional excipient to enhance the drug dissolution rate. The Liqui-Pellet formulation with 42% w/w NaHCO 3 released 76.4% of drug after 2 hours at pH 1.2, which was 14 times faster than the physical mixture pellet (5.5% drug release in 2 h). In general, a faster dissolution rate was observed with increasing NaHCO 3 concentration; however, there was a limit to this effect. Above a certain limit, the influence of NaHCO 3 on the dissolution rate lessened. The flowability test showed that all formulations have good to excellent flowability. Overall, this study demonstrates the flexibility of Liqui-Pellets in terms of formulation design, which in turn further supports the potential of Liqui-Pellets as the next generation oral dosage form.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813340","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, Andre Hermans, Nathan D. Contrella, B. Nickerson, Carrie A. Coutant, Christian Jede, S. Kao, D. Kou, Emmanuel Scheubel, Fredrik Winge, Johanna Milsmann, M. Mueller-Zsigmondy, N. Zaborenko
Quality control dissolution testing represents a key product performance test for solid oral dosage forms and is the most likely QC test to result in laboratory investigations because of the relatively complex relationship between the dissolution performance, the drug product properties, and the systems necessary to measure the quality attribute. The Dissolution Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) has pooled our collective knowledge to outline some common ways that dissolution methods can fail. Examples and case studies are given to highlight errors related to equipment, method, materials, measurement, people, and the environment. Best practices for building method understanding and avoiding the exemplified issues are discussed. Case studies highlight the importance of buffer preparation, potential impact of contamination of the dissolution medium, additive-induced degradation, risks in the use of automation, differences between dissolution systems, and the effect of filter selection. Investing in analyst training programs, understanding the capabilities of your equipment portfolio, and using well-designed studies for robustness and ruggedness will reduce dissolution method investigations and improve compliance and productivity during the method lifecycle.
{"title":"Dissolution Method Troubleshooting: An Industry Perspective","authors":"J. Mann, Andre Hermans, Nathan D. Contrella, B. Nickerson, Carrie A. Coutant, Christian Jede, S. Kao, D. Kou, Emmanuel Scheubel, Fredrik Winge, Johanna Milsmann, M. Mueller-Zsigmondy, N. Zaborenko","doi":"10.14227/dt290422p190","DOIUrl":"https://doi.org/10.14227/dt290422p190","url":null,"abstract":"Quality control dissolution testing represents a key product performance test for solid oral dosage forms and is the most likely QC test to result in laboratory investigations because of the relatively complex relationship between the dissolution performance, the drug product properties, and the systems necessary to measure the quality attribute. The Dissolution Working Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) has pooled our collective knowledge to outline some common ways that dissolution methods can fail. Examples and case studies are given to highlight errors related to equipment, method, materials, measurement, people, and the environment. Best practices for building method understanding and avoiding the exemplified issues are discussed. Case studies highlight the importance of buffer preparation, potential impact of contamination of the dissolution medium, additive-induced degradation, risks in the use of automation, differences between dissolution systems, and the effect of filter selection. Investing in analyst training programs, understanding the capabilities of your equipment portfolio, and using well-designed studies for robustness and ruggedness will reduce dissolution method investigations and improve compliance and productivity during the method lifecycle.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813605","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 February 2022","authors":"Margareth R. C. Marques, M. Liddell","doi":"10.14227/dt290122p46","DOIUrl":"https://doi.org/10.14227/dt290122p46","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813160","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}
Natália Olegário dos Santos, Nathalie R. Wingert, M. Steppe
Apixaban is an anticoagulant agent that inhibits factor Xa, commercially available as coated tablets at the dosages of 2.5 and 5.0 mg. There is no official monograph of the formulation in the current international pharmacopoeias. From research and development to finished product quality control, the dissolution test is an important tool to evaluate the quality of pharmaceutical formulations. This study aimed to develop and validate an in vitro method to assess the dissolution profile of apixaban immediate-release (5 mg) coated tablets. Several conditions were tested in this study until the most suitable one was reached. The selected method included the following parameters: 0.01 M hydrochloric acid (pH 2.3, 500 mL), USP paddle apparatus, 75 rpm, 37 °C, with seven sampling points and a total test time of 90 minutes. Quantitative analysis was performed by high performance liquid chromatography using a previously validated method. The dissolution method was validated following the official guidelines, demonstrating specificity, linearity, precision, accuracy, and robustness. This study enabled the development of an adequate, effective, and reliable method, which contributes to the evaluation of apixaban release in new products and the quality control of formulations containing this drug.
{"title":"Dissolution Profile of Apixaban Tablets: Method Development and Validation Using HPLC Analysis","authors":"Natália Olegário dos Santos, Nathalie R. Wingert, M. Steppe","doi":"10.14227/dt290122p22","DOIUrl":"https://doi.org/10.14227/dt290122p22","url":null,"abstract":"Apixaban is an anticoagulant agent that inhibits factor Xa, commercially available as coated tablets at the dosages of 2.5 and 5.0 mg. There is no official monograph of the formulation in the current international pharmacopoeias. From research and development to finished product quality control, the dissolution test is an important tool to evaluate the quality of pharmaceutical formulations. This study aimed to develop and validate an in vitro method to assess the dissolution profile of apixaban immediate-release (5 mg) coated tablets. Several conditions were tested in this study until the most suitable one was reached. The selected method included the following parameters: 0.01 M hydrochloric acid (pH 2.3, 500 mL), USP paddle apparatus, 75 rpm, 37 °C, with seven sampling points and a total test time of 90 minutes. Quantitative analysis was performed by high performance liquid chromatography using a previously validated method. The dissolution method was validated following the official guidelines, demonstrating specificity, linearity, precision, accuracy, and robustness. This study enabled the development of an adequate, effective, and reliable method, which contributes to the evaluation of apixaban release in new products and the quality control of formulations containing this drug.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813590","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 2022","authors":"Margareth R. C. Marques, M. Liddell","doi":"10.14227/dt290422p238","DOIUrl":"https://doi.org/10.14227/dt290422p238","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813787","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：