The purpose of this study was to establish the preparation process of ZGDHu-1 nanoparticles and to study its physicochemical properties. The nanoparticles were prepared using a high-pressure homogenization method. Natural phospholipid and soybean oil were used as drug carriers, and Cremophor EL was used as surfactant. The resulting nanoparticles had a spherical shape, with a mean ± SD particle size of 106.8 ± 15.9 nm, polydispersity index (PDI) of 0.136 ± 0.011, zeta potential of -63.97 ± 3.57 mV, encapsulation efficiency of 86.95%, and in vitro cumulative release rate of 84.67% in 24 hours. The nanoparticle preparation process was simple and reproducible. The nanoparticles had good physicochemical properties and in vitro release was improved by increasing solubility. This study provides a method for improving in vitro release for development of ZGDHu-1 nanoparticle formulations.
{"title":"Preparation and Characterization of ZGDHu-1 Nanoparticles","authors":"Lei Shi, Yong-li Liu, Kunlin Wu, Ruiz Si","doi":"10.14227/dt280321p40","DOIUrl":"https://doi.org/10.14227/dt280321p40","url":null,"abstract":"The purpose of this study was to establish the preparation process of ZGDHu-1 nanoparticles and to study its physicochemical properties. The nanoparticles were prepared using a high-pressure homogenization method. Natural phospholipid and soybean oil were used as drug carriers, and Cremophor EL was used as surfactant. The resulting nanoparticles had a spherical shape, with a mean ± SD particle size of 106.8 ± 15.9 nm, polydispersity index (PDI) of 0.136 ± 0.011, zeta potential of -63.97 ± 3.57 mV, encapsulation efficiency of 86.95%, and in vitro cumulative release rate of 84.67% in 24 hours. The nanoparticle preparation process was simple and reproducible. The nanoparticles had good physicochemical properties and in vitro release was improved by increasing solubility. This study provides a method for improving in vitro release for development of ZGDHu-1 nanoparticle formulations.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"35 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813181","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":"Book Review: “In Vitro Drug Release Testing of Special Dosage Forms,” Advances in Pharmaceutical Technology Series, Edited by Fotaki and Klein","authors":"G. Martin","doi":"10.14227/DT280221P42","DOIUrl":"https://doi.org/10.14227/DT280221P42","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"42-42"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66813375","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}
Omega-3 fatty acid soft capsules are a popular nutritional supplement. Previous product quality studies reported in the literature have mostly only addressed specifications for omega-3 fatty acid content and chemical stability aspects. This study aimed to characterize the in vitro release characteristics of omega-3 from soft capsules in aqueous media using disintegration and rupture tests. Four gelatin and one non-gelatin (starch/carrageen) commercially available omega-3 soft capsule products were evaluated using water and 0.1 N HCl as the media. In general, most products displayed faster release in the acidic medium compared to water. There was a statistically significant correlation between the disintegration and rupture test times. Although between-product disintegration and rupture test times varied considerably, all products ruptured within 15 minutes and completely disintegrated within 30 minutes in both media.
{"title":"Disintegration and Rupture Testing of Omega-3 Soft Capsules","authors":"N. Nyamweya, Teddy M. Mochama","doi":"10.14227/DT280121P6","DOIUrl":"https://doi.org/10.14227/DT280121P6","url":null,"abstract":"Omega-3 fatty acid soft capsules are a popular nutritional supplement. Previous product quality studies reported in the literature have mostly only addressed specifications for omega-3 fatty acid content and chemical stability aspects. This study aimed to characterize the in vitro release characteristics of omega-3 from soft capsules in aqueous media using disintegration and rupture tests. Four gelatin and one non-gelatin (starch/carrageen) commercially available omega-3 soft capsule products were evaluated using water and 0.1 N HCl as the media. In general, most products displayed faster release in the acidic medium compared to water. There was a statistically significant correlation between the disintegration and rupture test times. Although between-product disintegration and rupture test times varied considerably, all products ruptured within 15 minutes and completely disintegrated within 30 minutes in both media.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"6-11"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812776","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}
Biorelevant media, such as fasted state simulated intestinal fluid (FaSSIF), are often used to forecast in vivo behavior of oral solid formulations in the gastrointestinal tract. This study uses conventional surfactants (Tween 80 and sodium lauryl sulfate) and a model based on structural parameters (i.e., molecular descriptors) to evaluate possible alternatives to FaSSIF for solubility evaluation of three poorly soluble drugs. The solubility of enrofloxacin, lamotrigine, and phenobarbital was determined in phosphate buffer solution (PBS, pH 6.5) and FaSSIF. The molecular descriptors of drugs were computed, and a mathematical model based on logistic regression was generated to estimate solubilization in FaSSIF compared with PBS. The results demonstrated that solubility of enrofloxacin, lamotrigine, and phenobarbital in Tween 80 (0.1% w/v) was similar to their solubility in FaSSIF, and the proposed model calculated the solubilization ratio with 80% accuracy. In conclusion, Tween 80 in low concentration (i.e., 0.05%) is an appropriate low-cost alternative to FaSSIF, and the proposed model can be used to evaluate the possibility of solubilization in FaSSIF.
{"title":"Conventional Surfactants and a Model Based on Molecular Descriptors as Alternatives to the Drug Solubility in Fasted State Simulated Intestinal Fluid","authors":"Nahal Rahimi Ardabili, A. Shayanfar","doi":"10.14227/dt280321p32","DOIUrl":"https://doi.org/10.14227/dt280321p32","url":null,"abstract":"Biorelevant media, such as fasted state simulated intestinal fluid (FaSSIF), are often used to forecast in vivo behavior of oral solid formulations in the gastrointestinal tract. This study uses conventional surfactants (Tween 80 and sodium lauryl sulfate) and a model based on structural parameters (i.e., molecular descriptors) to evaluate possible alternatives to FaSSIF for solubility evaluation of three poorly soluble drugs. The solubility of enrofloxacin, lamotrigine, and phenobarbital was determined in phosphate buffer solution (PBS, pH 6.5) and FaSSIF. The molecular descriptors of drugs were computed, and a mathematical model based on logistic regression was generated to estimate solubilization in FaSSIF compared with PBS. The results demonstrated that solubility of enrofloxacin, lamotrigine, and phenobarbital in Tween 80 (0.1% w/v) was similar to their solubility in FaSSIF, and the proposed model calculated the solubilization ratio with 80% accuracy. In conclusion, Tween 80 in low concentration (i.e., 0.05%) is an appropriate low-cost alternative to FaSSIF, and the proposed model can be used to evaluate the possibility of solubilization in FaSSIF.","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":"66813170","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 the present study was to experimentally compare the attributes, drawbacks, and limitations of the most commonly employed in vitro drug release test methods for nanoparticle systems and to explore the possibility of one method being adopted as a standard for quality control of nanoparticle-based products. Three in vitro drug release test methods, i.e., direct addition, dialysis bag, and low-pressure ultrafiltration, were employed for evaluation of drug release from tamoxifen-loaded poly(lactic-co-glycolic acid) nanoparticles. Relevant operational characteristics of each test method were compared. Drug release data were fitted in different release kinetics models, i.e., zero order, first order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas. The coefficient of determination (R2), release rate constant (k), and release exponent (n) values were calculated. The direct addition method showed rapid initial drug release, whereas a slow release rate was observed in the dialysis bag method. Results of the low-pressure ultrafiltration method were consistent with the direct addition method and various operational characteristics were more realistic than the other two methods. Overall, the findings support that low-pressure ultrafiltration can be considered as a standard regulatory test method for in vitro release of nanoparticle-based formulations.
{"title":"Comparative Evaluation of In Vitro Drug Release Methods Employed for Nanoparticle Drug Release Studies","authors":"S. K. Paswan, T. Saini","doi":"10.14227/dt280421p30","DOIUrl":"https://doi.org/10.14227/dt280421p30","url":null,"abstract":"The aim of the present study was to experimentally compare the attributes, drawbacks, and limitations of the most commonly employed in vitro drug release test methods for nanoparticle systems and to explore the possibility of one method being adopted as a standard for quality control of nanoparticle-based products. Three in vitro drug release test methods, i.e., direct addition, dialysis bag, and low-pressure ultrafiltration, were employed for evaluation of drug release from tamoxifen-loaded poly(lactic-co-glycolic acid) nanoparticles. Relevant operational characteristics of each test method were compared. Drug release data were fitted in different release kinetics models, i.e., zero order, first order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas. The coefficient of determination (R2), release rate constant (k), and release exponent (n) values were calculated. The direct addition method showed rapid initial drug release, whereas a slow release rate was observed in the dialysis bag method. Results of the low-pressure ultrafiltration method were consistent with the direct addition method and various operational characteristics were more realistic than the other two methods. Overall, the findings support that low-pressure ultrafiltration can be considered as a standard regulatory test method for in vitro release of nanoparticle-based formulations.","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":"66813286","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 2021","authors":"Margareth R. C. Marques, M. Liddell","doi":"10.14227/DT280121P42","DOIUrl":"https://doi.org/10.14227/DT280121P42","url":null,"abstract":"","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"42-44"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812715","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}
Jose Raul MEDINA-LÓPEZ, Alexander Domínguez-Reyes, Marcela Hurtado
Dissolution studies are essential for comparing the quality of generic drugs to their reference products. The objective of this work was to evaluate the in vitro release of furosemide in tablets under official dissolution conditions and using the flow-through cell method. To this end, two USP apparatus were used: apparatus 2 (paddle at 50 rpm) containing 900 mL of phosphate buffer solution pH 5.8, and apparatus 4 (flow-through cell at 16 mL/min) with the same medium. The dissolved drug was quantified by UV spectrophotometry at 274 nm for 60 min. Although the results at a single time point met the acceptance criterion of Q = 80% at 60 min, the dissolution profiles of generic drugs were not similar to the reference product. The similarity factor (f2 < 50), mean dissolution time, dissolution efficiency, t50%, t80%, and Td values corroborate the difference between the profiles (p < 0.05). In vitro release testing demonstrates that, for furosemide tablets available in Mexico, the generic formulations perform differently from the reference products. These differences could affect in vivo absorption, which could yield different therapeutic effects. More evaluation of generic furosemide tablets manufactured in Mexico is needed.
{"title":"Comparison of Generic Furosemide Products by In Vitro Release Studies using USP Apparatus 2 and 4","authors":"Jose Raul MEDINA-LÓPEZ, Alexander Domínguez-Reyes, Marcela Hurtado","doi":"10.14227/DT280121P14","DOIUrl":"https://doi.org/10.14227/DT280121P14","url":null,"abstract":"Dissolution studies are essential for comparing the quality of generic drugs to their reference products. The objective of this work was to evaluate the in vitro release of furosemide in tablets under official dissolution conditions and using the flow-through cell method. To this end, two USP apparatus were used: apparatus 2 (paddle at 50 rpm) containing 900 mL of phosphate buffer solution pH 5.8, and apparatus 4 (flow-through cell at 16 mL/min) with the same medium. The dissolved drug was quantified by UV spectrophotometry at 274 nm for 60 min. Although the results at a single time point met the acceptance criterion of Q = 80% at 60 min, the dissolution profiles of generic drugs were not similar to the reference product. The similarity factor (f2 < 50), mean dissolution time, dissolution efficiency, t50%, t80%, and Td values corroborate the difference between the profiles (p < 0.05). In vitro release testing demonstrates that, for furosemide tablets available in Mexico, the generic formulations perform differently from the reference products. These differences could affect in vivo absorption, which could yield different therapeutic effects. More evaluation of generic furosemide tablets manufactured in Mexico is needed.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"28 1","pages":"14-22"},"PeriodicalIF":0.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812834","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, Juan J. Palomino-Jhong, Jorge A. García, César André Alvarado, E. Alvarado, Gaby Ochoa-Pachas, Mario Pineda-Pérez, Mario Bolarte
Carbamazepine is an antiepileptic iminostilbene that is dispensed from multiple sources in Peru without bioequivalence studies. The biopharmaceutical equivalence of two generic (A and B) and one commercial brand (C) of carbamazepine sodium as compared to the innovator drug was determined by an in vitro study of commercial 200-mg tablets, following the guidelines of the Biopharmaceutical Classification System. Hardness, weight, friability, and content were evaluated for compliance with official specifications. A United States Pharmacopeia (USP) dissolution apparatus 2 (paddle) was used at with 900 mL of medium (pH 1.2, 4.5, and 6.8) at 75 rpm and 37 ± 0.5 °C. Samples (5 mL) were withdrawn at 5, 10, 15, 30, 45, 60, and 90 minutes and analyzed in a UV spectrophotometer at 288 nm. The studied drugs did not release 85% of the active pharmaceutical ingredient within 30 minutes in any media. When compared to the innovator brand using the similarity factor ( f 2 ), product A was < 50 at all three pH levels; B was < 50 at pH 4.5, and C was < 50 at pH 1.2 and 4.5. For all products, dissolution efficiency was 56.1–84.3% and mean dissolution time was 18.0–47.5 min. Despite meeting the official specifications for quality control tests, the evaluated samples are not in vitro biopharmaceutical equivalents with the innovator brand based on the dissolution profiles ( f 2 < 50).
{"title":"In Vitro Biopharmaceutical Equivalence of Carbamazepine Sodium Tablets Available in Lima, Peru","authors":"Angel T. Alvarado, A. M. Muñoz, M. Bendezu, Juan J. Palomino-Jhong, Jorge A. García, César André Alvarado, E. Alvarado, Gaby Ochoa-Pachas, Mario Pineda-Pérez, Mario Bolarte","doi":"10.14227/DT280221PGC2","DOIUrl":"https://doi.org/10.14227/DT280221PGC2","url":null,"abstract":"Carbamazepine is an antiepileptic iminostilbene that is dispensed from multiple sources in Peru without bioequivalence studies. The biopharmaceutical equivalence of two generic (A and B) and one commercial brand (C) of carbamazepine sodium as compared to the innovator drug was determined by an in vitro study of commercial 200-mg tablets, following the guidelines of the Biopharmaceutical Classification System. Hardness, weight, friability, and content were evaluated for compliance with official specifications. A United States Pharmacopeia (USP) dissolution apparatus 2 (paddle) was used at with 900 mL of medium (pH 1.2, 4.5, and 6.8) at 75 rpm and 37 ± 0.5 °C. Samples (5 mL) were withdrawn at 5, 10, 15, 30, 45, 60, and 90 minutes and analyzed in a UV spectrophotometer at 288 nm. The studied drugs did not release 85% of the active pharmaceutical ingredient within 30 minutes in any media. When compared to the innovator brand using the similarity factor ( f 2 ), product A was < 50 at all three pH levels; B was < 50 at pH 4.5, and C was < 50 at pH 1.2 and 4.5. For all products, dissolution efficiency was 56.1–84.3% and mean dissolution time was 18.0–47.5 min. Despite meeting the official specifications for quality control tests, the evaluated samples are not in vitro biopharmaceutical equivalents with the innovator brand based on the dissolution profiles ( f 2 < 50).","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":"66813477","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}
Andre Hermans, P. Dorożyński, F. Muzzio, Hanlin Li, Sarah Nielsen, Shirlynn Chen, C. Reppas, S. Klein, Sanjaykumar Patel, M. Wacker, K. Thakker, Katharina Pruessmann, Anne Seidlitz, T. Ghosh, Yang Yang, Daniel R Willett, G. Hochhaus, J. Tay, C. Liew, P. Heng, Changquan Calvin Sun, John C. Kraemer, Margareth R. C. Marques
In December 2019, The United States Pharmacopeia (USP) organized a 2-day workshop to explore new approaches to assess in vitro performance of drug products. Experts from around the globe presented processes, techniques, systems that can be used to evaluate and model in vitro performance of different pharmaceutical dosage forms. The following is a summary of most of the presentations and the highlights of the discussions that ensued. Disclaimer: This article reflects the views of the authors and should not be construed as representing the views or policies of the United States Food and Drug Administration.
{"title":"Workshop Report: USP Workshop on Advancements in In Vitro Performance Testing of Drug Products","authors":"Andre Hermans, P. Dorożyński, F. Muzzio, Hanlin Li, Sarah Nielsen, Shirlynn Chen, C. Reppas, S. Klein, Sanjaykumar Patel, M. Wacker, K. Thakker, Katharina Pruessmann, Anne Seidlitz, T. Ghosh, Yang Yang, Daniel R Willett, G. Hochhaus, J. Tay, C. Liew, P. Heng, Changquan Calvin Sun, John C. Kraemer, Margareth R. C. Marques","doi":"10.14227/dt270220p52","DOIUrl":"https://doi.org/10.14227/dt270220p52","url":null,"abstract":"In December 2019, The United States Pharmacopeia (USP) organized a 2-day workshop to explore new approaches to assess in vitro performance of drug products. Experts from around the globe presented processes, techniques, systems that can be used to evaluate and model in vitro performance of different pharmaceutical dosage forms. The following is a summary of most of the presentations and the highlights of the discussions that ensued. Disclaimer: This article reflects the views of the authors and should not be construed as representing the views or policies of the United States Food and Drug Administration.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"52-70"},"PeriodicalIF":0.6,"publicationDate":"2020-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45988265","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 article is to inform the dissolution scientist of a powerful emerging tool that provides in vivo linkage to dissolution methods. This tool is physiologically based biopharmaceutics modelling (PBBM). Dissolution scientists are mostly concerned with analytical sections of drug development, so exposure to modeling and other pharmacokinetics and biopharmaceutic concepts may be uncommon. PBBM is an in-silico model that focuses on the interactions between the in vivo physiology and the formulation and drug characteristics. The principles behind PBBM is that all mechanisms related to drug release, dissolution, and diffusion from the site of administration to the site of action can be described in a mechanistic way or semi-empirical way. The integration of in vitro dissolution data in PBBM is described, including examples of software and modeling applications. The expertise needed to use the software and appropriate training is discussed. The key inputs that are expected from the dissolution scientist include an understanding of the aqueous solubility across the physiological pH range, impact of in vivo relevant bile salts and phospholipids on solubilization, and the impact of surface pH on dissolution rate. An example of an advanced in vitro system, TNO intestinal model (TIM-1), will be discussed and its importance in establishing a biorelevant understanding of dissolution behavior. PBBM can evaluate the clinical relevance of a dissolution method and justify specifications and ultimately provide an approval advantage to the sponsor. A well-supported dissolution method that provides clinically relevant drug product specifications (CRDPS) will be viewed with favor by the regulators. Therefore, the partnering of a dissolution scientist and biopharmaceutics scientist to develop PBBM is clearly an important step forward in drug development.
{"title":"The Case for Physiologically Based Biopharmaceutics Modelling (PBBM): What do Dissolution Scientists Need to Know?","authors":"V. Gray, J. Mann, Ric Barker, X. Pepin","doi":"10.14227/dt270320p6","DOIUrl":"https://doi.org/10.14227/dt270320p6","url":null,"abstract":"The purpose of this article is to inform the dissolution scientist of a powerful emerging tool that provides in vivo linkage to dissolution methods. This tool is physiologically based biopharmaceutics modelling (PBBM). Dissolution scientists are mostly concerned with analytical sections of drug development, so exposure to modeling and other pharmacokinetics and biopharmaceutic concepts may be uncommon. PBBM is an in-silico model that focuses on the interactions between the in vivo physiology and the formulation and drug characteristics. The principles behind PBBM is that all mechanisms related to drug release, dissolution, and diffusion from the site of administration to the site of action can be described in a mechanistic way or semi-empirical way. The integration of in vitro dissolution data in PBBM is described, including examples of software and modeling applications. The expertise needed to use the software and appropriate training is discussed. The key inputs that are expected from the dissolution scientist include an understanding of the aqueous solubility across the physiological pH range, impact of in vivo relevant bile salts and phospholipids on solubilization, and the impact of surface pH on dissolution rate. An example of an advanced in vitro system, TNO intestinal model (TIM-1), will be discussed and its importance in establishing a biorelevant understanding of dissolution behavior. PBBM can evaluate the clinical relevance of a dissolution method and justify specifications and ultimately provide an approval advantage to the sponsor. A well-supported dissolution method that provides clinically relevant drug product specifications (CRDPS) will be viewed with favor by the regulators. Therefore, the partnering of a dissolution scientist and biopharmaceutics scientist to develop PBBM is clearly an important step forward in drug development.","PeriodicalId":11380,"journal":{"name":"Dissolution Technologies","volume":"27 1","pages":"6-19"},"PeriodicalIF":0.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66812689","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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