Cargando…

Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

Dissolution testing is a major tool used to assess a drug product’s performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity med...

Descripción completa

Detalles Bibliográficos
Autores principales: Amaral Silva, Daniela, Al-Gousous, Jozef, Davies, Neal M., Bou Chacra, Nadia, Webster, Gregory K., Lipka, Elke, Amidon, Gordon L., Löbenberg, Raimar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284338/
https://www.ncbi.nlm.nih.gov/pubmed/32370237
http://dx.doi.org/10.3390/pharmaceutics12050420
_version_ 1783544443269283840
author Amaral Silva, Daniela
Al-Gousous, Jozef
Davies, Neal M.
Bou Chacra, Nadia
Webster, Gregory K.
Lipka, Elke
Amidon, Gordon L.
Löbenberg, Raimar
author_facet Amaral Silva, Daniela
Al-Gousous, Jozef
Davies, Neal M.
Bou Chacra, Nadia
Webster, Gregory K.
Lipka, Elke
Amidon, Gordon L.
Löbenberg, Raimar
author_sort Amaral Silva, Daniela
collection PubMed
description Dissolution testing is a major tool used to assess a drug product’s performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance.
format Online
Article
Text
id pubmed-7284338
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72843382020-08-13 Biphasic Dissolution as an Exploratory Method during Early Drug Product Development Amaral Silva, Daniela Al-Gousous, Jozef Davies, Neal M. Bou Chacra, Nadia Webster, Gregory K. Lipka, Elke Amidon, Gordon L. Löbenberg, Raimar Pharmaceutics Article Dissolution testing is a major tool used to assess a drug product’s performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance. MDPI 2020-05-02 /pmc/articles/PMC7284338/ /pubmed/32370237 http://dx.doi.org/10.3390/pharmaceutics12050420 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Amaral Silva, Daniela
Al-Gousous, Jozef
Davies, Neal M.
Bou Chacra, Nadia
Webster, Gregory K.
Lipka, Elke
Amidon, Gordon L.
Löbenberg, Raimar
Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title_full Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title_fullStr Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title_full_unstemmed Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title_short Biphasic Dissolution as an Exploratory Method during Early Drug Product Development
title_sort biphasic dissolution as an exploratory method during early drug product development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284338/
https://www.ncbi.nlm.nih.gov/pubmed/32370237
http://dx.doi.org/10.3390/pharmaceutics12050420
work_keys_str_mv AT amaralsilvadaniela biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT algousousjozef biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT daviesnealm biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT bouchacranadia biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT webstergregoryk biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT lipkaelke biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT amidongordonl biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment
AT lobenbergraimar biphasicdissolutionasanexploratorymethodduringearlydrugproductdevelopment