V. Jouyban-Gharamaleki, F. Martínez, M. Kuentz, E. Rahimpour, A. Jouyban
In the current work, a laser monitoring technique was used to study dissolution and solubility of celecoxib (CBX) in 2-propanol and propylene glycol mixtures at temperatures of 293.2–313.2 K. The solubility data were fitted to mathematical models, i.e., the van’t Hoff model, the mixture surface model, the Jouyban-Acree and Jouyban-Acree-van’t Hoff equations, and the modified Wilson model. Model accuracy was evaluated by mean relative deviation (MRD%) for back-calculated solubility values. The thermodynamic behavior of CBX dissolution was evaluated according to the van’t Hoff and Gibbs equations. CBX exhibited maximum solubility in 2-propanol with a mass fraction of 0.8 at all temperatures. CBX dissolution was identified as an endothermic and enthalpy-driven process, which was more favorable in mixtures with high drug solubilizing capacity. The various models described solubility data from the laser monitoring technique adequately, and the studied cosolvent mixtures have the potential to be used in analytical pharmaceutical development or as intermediate bulk solutions for CBX products.
{"title":"Using a Laser Monitoring Technique for Dissolution and Thermodynamic Study of Celecoxib in 2-Propanol and Propylene Glycol Mixtures","authors":"V. Jouyban-Gharamaleki, F. Martínez, M. Kuentz, E. Rahimpour, A. Jouyban","doi":"10.14227/dt300223p80","DOIUrl":"https://doi.org/10.14227/dt300223p80","url":null,"abstract":"In the current work, a laser monitoring technique was used to study dissolution and solubility of celecoxib (CBX) in 2-propanol and propylene glycol mixtures at temperatures of 293.2–313.2 K. The solubility data were fitted to mathematical models, i.e., the van’t Hoff model, the mixture surface model, the Jouyban-Acree and Jouyban-Acree-van’t Hoff equations, and the modified Wilson model. Model accuracy was evaluated by mean relative deviation (MRD%) for back-calculated solubility values. The thermodynamic behavior of CBX dissolution was evaluated according to the van’t Hoff and Gibbs equations. CBX exhibited maximum solubility in 2-propanol with a mass fraction of 0.8 at all temperatures. CBX dissolution was identified as an endothermic and enthalpy-driven process, which was more favorable in mixtures with high drug solubilizing capacity. The various models described solubility data from the laser monitoring technique adequately, and the studied cosolvent mixtures have the potential to be used in analytical pharmaceutical development or as intermediate bulk solutions for CBX products.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66814228","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}
Hanlin Li, lshai Nir, Andre Hermans, R. Fahmy, Xujin Lu, Carrie A. Coutant
As continuous manufacturing (CM) evolves from an emerging to widely adopted technology by industry in drug product manufacturing, the compendiaI framework in product performance testing is also being evaluated for its applicability in CM. As such, the CM Working Group of the New Advancements in Product Performance Testing (NAPPT) Expert Panel was convened in 2019 to review the current standard for product performance testing, identify gaps in its applicability to CM, and recommend the development of new standards to support the adoption of advancing technologies industry-wide. This Stimuli article discusses the challenges and limitations of the current performance testing by dissolution for CM applications. It also presents recommendations on alternatives or surrogate methods, including in/at-line process analytical technology methods, with a decision tree to support users in identifying an option that is fit for their process. The Expert Panel seeks stakeholder feedback on the recommendations presented in this Stimuli article, and requests additional comments on the perceived challenges and limitations of performance testing.
{"title":"In Vitro Performance Tests for Continuous Manufacturing: The Impact on the Current Compendial Framework from the Viewpoint of the USP New Advancements in Product Performance Testing Expert Panel","authors":"Hanlin Li, lshai Nir, Andre Hermans, R. Fahmy, Xujin Lu, Carrie A. Coutant","doi":"10.14227/dt300123p6","DOIUrl":"https://doi.org/10.14227/dt300123p6","url":null,"abstract":"As continuous manufacturing (CM) evolves from an emerging to widely adopted technology by industry in drug product manufacturing, the compendiaI framework in product performance testing is also being evaluated for its applicability in CM. As such, the CM Working Group of the New Advancements in Product Performance Testing (NAPPT) Expert Panel was convened in 2019 to review the current standard for product performance testing, identify gaps in its applicability to CM, and recommend the development of new standards to support the adoption of advancing technologies industry-wide. This Stimuli article discusses the challenges and limitations of the current performance testing by dissolution for CM applications. It also presents recommendations on alternatives or surrogate methods, including in/at-line process analytical technology methods, with a decision tree to support users in identifying an option that is fit for their process. The Expert Panel seeks stakeholder feedback on the recommendations presented in this Stimuli article, and requests additional comments on the perceived challenges and limitations of performance testing.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66814589","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 technology has recently been developed and has shown to be promising in achieving a rapid drug release rate with water insoluble drugs. At present, only naproxen and ketoprofen have been applied to an oral solid dosage form for immediate release. The present investigation aims to explore the drug release performance of the poorly water-soluble hydrochlorothiazide (HCTZ) using the Liqui-Pellet technology. Various non-volatile co-solvents such as Tween 80, PG, Kolliphor EL, and PEG 200 were used to make HCTZ Liqui-Pellet formulations to investigate the influence of Liqui-Pellet technology on the drug release profile. Saturation solubility studies showed HCTZ was most soluble in PEG 200 (156 mg/mL), which is also reflected in the drug release data where HCTZ Liqui-Pellet containing PEG 200 had the most enhanced drug dissolution profile. A binary mixture of carriers consisting of Avicel PH-101 and Neusilin US2 was investigated, as this mixture has been shown to improve drug release rate in a previous study. Surprisingly, the binary mixture of carriers did not improve the drug release rate in this study. The best formulation reached 100% drug release at approximately 40 min. Other physicochemical analysis tests showed the Liqui-Pellets’ flow property, robustness, and size distribution are generally acceptable and pose no major issue in terms of manufacturing. In conclusion, the Liqui-Mass system combined with extrusion-spheronization is a viable approach to enhance HCTZ dissolution.
{"title":"The Combination of Liqui-Mass System and Pelletization to Improve Pharmaceutical Properties of Hydrochlorothiazide","authors":"Matthew Lam, A. Nokhodchi","doi":"10.14227/dt290322p128","DOIUrl":"https://doi.org/10.14227/dt290322p128","url":null,"abstract":"Liqui-Pellet technology has recently been developed and has shown to be promising in achieving a rapid drug release rate with water insoluble drugs. At present, only naproxen and ketoprofen have been applied to an oral solid dosage form for immediate release. The present investigation aims to explore the drug release performance of the poorly water-soluble hydrochlorothiazide (HCTZ) using the Liqui-Pellet technology. Various non-volatile co-solvents such as Tween 80, PG, Kolliphor EL, and PEG 200 were used to make HCTZ Liqui-Pellet formulations to investigate the influence of Liqui-Pellet technology on the drug release profile. Saturation solubility studies showed HCTZ was most soluble in PEG 200 (156 mg/mL), which is also reflected in the drug release data where HCTZ Liqui-Pellet containing PEG 200 had the most enhanced drug dissolution profile. A binary mixture of carriers consisting of Avicel PH-101 and Neusilin US2 was investigated, as this mixture has been shown to improve drug release rate in a previous study. Surprisingly, the binary mixture of carriers did not improve the drug release rate in this study. The best formulation reached 100% drug release at approximately 40 min. Other physicochemical analysis tests showed the Liqui-Pellets’ flow property, robustness, and size distribution are generally acceptable and pose no major issue in terms of manufacturing. In conclusion, the Liqui-Mass system combined with extrusion-spheronization is a viable approach to enhance HCTZ dissolution.","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":"66813453","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, V. Gray, A. M. Muñoz, María Saravia, María R. Bendezú, H. Chávez, Jorge A. García, R. Ybañez-Julca, Andres Chonn-Chang, Patricia Basurto, Mario Pineda-Pérez, Alberto Salazar
This is a review of the current status of drug bioequivalence studies in Peru. A bibliographic search was conducted in PubMed (Medline database) for bioequivalence studies in Peru. Generic drugs constitute the basis of pharmacological requests in health care systems in Latin American countries. Peru has enacted laws and regulations that require bioequivalence studies of high health risk drugs and exemptions, based on international legislation, to be conducted in research centers accredited by the authority of Health. There is a list of 19 drugs that must demonstrate their therapeutic equivalence through in vivo or in vitro studies, of which 13 have shown bioequivalence in vivo, and 8 of those have shown bioequivalence in vitro. There is a challenge for health authorities to enforce the current legislation and an even greater challenge for pharmaceutical laboratories to demonstrate bioequivalence of multi-source drugs with the reference drug.
{"title":"Review: Application of Bioequivalence Testing of Medicines in Peru","authors":"Angel T. Alvarado, V. Gray, A. M. Muñoz, María Saravia, María R. Bendezú, H. Chávez, Jorge A. García, R. Ybañez-Julca, Andres Chonn-Chang, Patricia Basurto, Mario Pineda-Pérez, Alberto Salazar","doi":"10.14227/dt290422p220","DOIUrl":"https://doi.org/10.14227/dt290422p220","url":null,"abstract":"This is a review of the current status of drug bioequivalence studies in Peru. A bibliographic search was conducted in PubMed (Medline database) for bioequivalence studies in Peru. Generic drugs constitute the basis of pharmacological requests in health care systems in Latin American countries. Peru has enacted laws and regulations that require bioequivalence studies of high health risk drugs and exemptions, based on international legislation, to be conducted in research centers accredited by the authority of Health. There is a list of 19 drugs that must demonstrate their therapeutic equivalence through in vivo or in vitro studies, of which 13 have shown bioequivalence in vivo, and 8 of those have shown bioequivalence in vitro. There is a challenge for health authorities to enforce the current legislation and an even greater challenge for pharmaceutical laboratories to demonstrate bioequivalence of multi-source drugs with the reference 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":"66813667","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. A. Varillas, Marta I. V. Brevedan, N. G. Gonzalez Vidal
Losartan potassium (LOK) is an antihypertensive agent from the group of selective angiotensin AT1 receptor antagonists, widely used in the form of tablets for oral administration. The available data for BCS classification are confusing, though class III or IV are most likely. The quality attributes of solid oral dosage forms of LOK immediate-release tablets (50 mg) available in the Argentine pharmaceutical market were evaluated according to the Argentine Pharmacopoeia and United States Pharmacopeia (i.e., storage conditions information, price per tablet, average weight, assay, uniformity of dosage units, hardness, disintegration time, and in vitro dissolution). The dissolution efficiency (DE) results were compared using one way analysis of variance. All evaluated samples were within the acceptable limits for disintegration time, hardness, assay, uniformity of dosage units, and in vitro dissolution (in Stage 1). A statistically significant difference in DE was recorded for samples C, D, E, F, and G compared to the reference formulation (sample H). These samples had higher DE values than the reference; there were no statistically significant differences between the samples. Therefore, the evaluated samples of LOK from the Argentine market can be considered pharmaceutical equivalents.
{"title":"Pharmaceutical Equivalence of Losartan Potassium Tablets in Argentina","authors":"M. A. Varillas, Marta I. V. Brevedan, N. G. Gonzalez Vidal","doi":"10.14227/dt290222pgc2","DOIUrl":"https://doi.org/10.14227/dt290222pgc2","url":null,"abstract":"Losartan potassium (LOK) is an antihypertensive agent from the group of selective angiotensin AT1 receptor antagonists, widely used in the form of tablets for oral administration. The available data for BCS classification are confusing, though class III or IV are most likely. The quality attributes of solid oral dosage forms of LOK immediate-release tablets (50 mg) available in the Argentine pharmaceutical market were evaluated according to the Argentine Pharmacopoeia and United States Pharmacopeia (i.e., storage conditions information, price per tablet, average weight, assay, uniformity of dosage units, hardness, disintegration time, and in vitro dissolution). The dissolution efficiency (DE) results were compared using one way analysis of variance. All evaluated samples were within the acceptable limits for disintegration time, hardness, assay, uniformity of dosage units, and in vitro dissolution (in Stage 1). A statistically significant difference in DE was recorded for samples C, D, E, F, and G compared to the reference formulation (sample H). These samples had higher DE values than the reference; there were no statistically significant differences between the samples. Therefore, the evaluated samples of LOK from the Argentine market can be considered pharmaceutical equivalents.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"45 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813429","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}
Malaz Yousef, Chulhun Park, T. Le, Nadia Bou Chacra, Neil Davies, R. Löbenberg
In addition to removing excess extracellular fluid and mobilizing immune cells throughout the body, lymphatic fluid provides a means for drug transport. Lymphatic drug delivery can impart higher efficacy and bioavailability, especially following oral administration. Currently, there is no standardized composition for simulated lymphatic fluid. Standardization of a simulated lymphatic fluid media would be an important and novel contribution to fill the current void in this emerging area of drug and formulation development. This study aims to review and analyze the composition and flow rate of prepared simulated lymphatic fluid with comparison to commercially available artificial fluid and biological fluid. The prepared simulated fluids were closer in makeup to biological fluid than the commercial artificial fluid, which suggests potential benefits for developing and optimizing lymphotropic formulations for in vitro studies.
{"title":"Simulated Lymphatic Fluid for In-Vitro Assessment in Pharmaceutical Development","authors":"Malaz Yousef, Chulhun Park, T. Le, Nadia Bou Chacra, Neil Davies, R. Löbenberg","doi":"10.14227/dt290222p86","DOIUrl":"https://doi.org/10.14227/dt290222p86","url":null,"abstract":"In addition to removing excess extracellular fluid and mobilizing immune cells throughout the body, lymphatic fluid provides a means for drug transport. Lymphatic drug delivery can impart higher efficacy and bioavailability, especially following oral administration. Currently, there is no standardized composition for simulated lymphatic fluid. Standardization of a simulated lymphatic fluid media would be an important and novel contribution to fill the current void in this emerging area of drug and formulation development. This study aims to review and analyze the composition and flow rate of prepared simulated lymphatic fluid with comparison to commercially available artificial fluid and biological fluid. The prepared simulated fluids were closer in makeup to biological fluid than the commercial artificial fluid, which suggests potential benefits for developing and optimizing lymphotropic formulations for in vitro studies.","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":"66813302","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}
N. Zaborenko, Tessa M. Carducci, A. Ryckaert, H. Mandula, Matthew J. Walworth, Casey J. Smith, Sandra Suarez-Sharp, Melanie Dumarey, S. Manteiga, Sarah Nielsen, S. Altan, Adriene Malsbury, B. Nickerson, Yanmei Lan
To date, few examples of dissolution models for real-time release testing (RTRT) have been approved for commercial drug products or published in literature. Thus, a structured approach has not been established by which a novice to the field could design, develop, validate, and implement an RTRT dissolution model. Moreover, with scant examples available, there has not been a body of work by which to learn of general regulatory expectations for such models. To address these gaps and to encourage conversation between regulatory and industrial experts on these topics, a virtual (web-based) workshop entitled “Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation” was held November 11–12, 2021. This article summarizes key points from the podium presentations, panel discussions, and breakout sessions focusing on (1) the current best practices to establish predictive model specifications; (2) designing models to predict the “safe space” of a release test and creating models utilizing process analytical technology (PAT); and (3) exploring the strategy of compliant regulatory submissions, including model validation and post-approval lifecycle management. Industrial case studies were presented showcasing attempted approaches to and successful implementations of RTRT of dissolution for drug product manufacturing. Dissolution Profiles from Process Parameters, Formulation, and Spectroscopic of how certain affect linkage their variation and the effect on different parameters of the PDM. Spectroscopic PAT can capture individual tablet differences and incorporate it into
{"title":"Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation - Workshop Summary Report","authors":"N. Zaborenko, Tessa M. Carducci, A. Ryckaert, H. Mandula, Matthew J. Walworth, Casey J. Smith, Sandra Suarez-Sharp, Melanie Dumarey, S. Manteiga, Sarah Nielsen, S. Altan, Adriene Malsbury, B. Nickerson, Yanmei Lan","doi":"10.14227/dt290322p150","DOIUrl":"https://doi.org/10.14227/dt290322p150","url":null,"abstract":"To date, few examples of dissolution models for real-time release testing (RTRT) have been approved for commercial drug products or published in literature. Thus, a structured approach has not been established by which a novice to the field could design, develop, validate, and implement an RTRT dissolution model. Moreover, with scant examples available, there has not been a body of work by which to learn of general regulatory expectations for such models. To address these gaps and to encourage conversation between regulatory and industrial experts on these topics, a virtual (web-based) workshop entitled “Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation” was held November 11–12, 2021. This article summarizes key points from the podium presentations, panel discussions, and breakout sessions focusing on (1) the current best practices to establish predictive model specifications; (2) designing models to predict the “safe space” of a release test and creating models utilizing process analytical technology (PAT); and (3) exploring the strategy of compliant regulatory submissions, including model validation and post-approval lifecycle management. Industrial case studies were presented showcasing attempted approaches to and successful implementations of RTRT of dissolution for drug product manufacturing. Dissolution Profiles from Process Parameters, Formulation, and Spectroscopic of how certain affect linkage their variation and the effect on different parameters of the PDM. Spectroscopic PAT can capture individual tablet differences and incorporate it into","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":"66813531","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}
Marta I. V. Brevedan, M. A. Varillas, N. G. Gonzalez Vidal
Similarity studies are used with the intention to establish interchangeability of certain formulations in vitro, without the need to carry out in vivo studies. This interchangeability between formulations should be conserved during the product shelf life, as an integral part of the pharmaceutical stability. Hydrochlorothiazide (HCTZ), a widely used diuretic, is classified as a class 3 drug in the Biopharmaceutics Classification System (BCS). An immediate-release (IR) solid oral formulation containing a class 3 drug is a candidate for biowaiver if it meets the requirement of ῾ very rapid dissolution’ (i.e., ≥ 85% dissolved within 15 minutes). This research aimed to compare four solid oral IR HCTZ formulations (50 mg), commercially available in Argentina, with respect to pharmaceutical similarity and stability. To assess for similarity, dissolution profiles were compared both at time zero (T0) and after 12 months of storage (T12) at pH 1.2, 4.5, and 6.8. To assess for stability, critical quality attributes (CQAs) of the samples were evaluated at T12 of storage (25 °C, 60% relative humidity). At T12, all samples met the requirements for CQAs (i.e., assay, friability, disintegration, uniformity, and dissolution). The reference formulation had the fastest dissolution rate, and sample D was the slowest. Two multisource formulations exhibited statistical differences with respect to the reference sample, both at T0 and T12.
{"title":"Influence of Storage Conditions on Pharmaceutical Equivalence and Similarity of Hydrochlorothiazide Tablets in Argentina","authors":"Marta I. V. Brevedan, M. A. Varillas, N. G. Gonzalez Vidal","doi":"10.14227/dt290422pgc1","DOIUrl":"https://doi.org/10.14227/dt290422pgc1","url":null,"abstract":"Similarity studies are used with the intention to establish interchangeability of certain formulations in vitro, without the need to carry out in vivo studies. This interchangeability between formulations should be conserved during the product shelf life, as an integral part of the pharmaceutical stability. Hydrochlorothiazide (HCTZ), a widely used diuretic, is classified as a class 3 drug in the Biopharmaceutics Classification System (BCS). An immediate-release (IR) solid oral formulation containing a class 3 drug is a candidate for biowaiver if it meets the requirement of ῾ very rapid dissolution’ (i.e., ≥ 85% dissolved within 15 minutes). This research aimed to compare four solid oral IR HCTZ formulations (50 mg), commercially available in Argentina, with respect to pharmaceutical similarity and stability. To assess for similarity, dissolution profiles were compared both at time zero (T0) and after 12 months of storage (T12) at pH 1.2, 4.5, and 6.8. To assess for stability, critical quality attributes (CQAs) of the samples were evaluated at T12 of storage (25 °C, 60% relative humidity). At T12, all samples met the requirements for CQAs (i.e., assay, friability, disintegration, uniformity, and dissolution). The reference formulation had the fastest dissolution rate, and sample D was the slowest. Two multisource formulations exhibited statistical differences with respect to the reference sample, both at T0 and T12.","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":"66813864","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}
Khabbaz Choukri, El Orche Aimen, Cheikh Amine, Bouchafra Houda, Moulay El Abbes Faouzi, Cherrah Yahya, Boussen Ratiba, M. Bouatia
A novel approach to test the similarity of clopidogrel batches by comparing drug dissolution profiles, based on the combination of principal component analysis with hierarchical cluster analysis (PCA-HCA), is presented. Dissolution curves corresponding to five brands of clopidogrel drugs, taken as model drugs, were prepared by measuring the dissolution rate in pH 1.2, 4.5, and 6.8). The dissolution data were analyzed by similarity factor ( f 2 ) calculation and the PCA-HCA method, and the results were compared. Unlike the f 2 test, the PCA-HCA approach reflects the variability inside the individual dissolution patterns, which it is also sensitive to profile variations (form and size). The comparison between the PCA-HCA results with those of f 2 tests gives approximately similar results, knowing that PCA-HCA represents, in general, a more discriminative criterion.
{"title":"Contribution of Multivariate Analysis to the In Vitro Dissolution Profile for Testing Clopidogrel Drugs Similarity","authors":"Khabbaz Choukri, El Orche Aimen, Cheikh Amine, Bouchafra Houda, Moulay El Abbes Faouzi, Cherrah Yahya, Boussen Ratiba, M. Bouatia","doi":"10.14227/dt290322p138","DOIUrl":"https://doi.org/10.14227/dt290322p138","url":null,"abstract":"A novel approach to test the similarity of clopidogrel batches by comparing drug dissolution profiles, based on the combination of principal component analysis with hierarchical cluster analysis (PCA-HCA), is presented. Dissolution curves corresponding to five brands of clopidogrel drugs, taken as model drugs, were prepared by measuring the dissolution rate in pH 1.2, 4.5, and 6.8). The dissolution data were analyzed by similarity factor ( f 2 ) calculation and the PCA-HCA method, and the results were compared. Unlike the f 2 test, the PCA-HCA approach reflects the variability inside the individual dissolution patterns, which it is also sensitive to profile variations (form and size). The comparison between the PCA-HCA results with those of f 2 tests gives approximately similar results, knowing that PCA-HCA represents, in general, a more discriminative criterion.","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":"66813518","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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