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Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release

Recent work has highlighted that amorphous solid dispersions (ASDs) containing delamanid (DLM) and an enteric polymer, hypromellose phthalate (HPMCP), appear to be susceptible to crystallization during immersion in simulated gastric fluids. The goal of this study was to minimize contact of the ASD p...

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Autores principales: Nguyen, Hanh Thuy, Van Duong, Tu, Taylor, Lynne S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier/North-Holland Biomedical Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390825/
https://www.ncbi.nlm.nih.gov/pubmed/37311499
http://dx.doi.org/10.1016/j.ijpharm.2023.123139
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author Nguyen, Hanh Thuy
Van Duong, Tu
Taylor, Lynne S.
author_facet Nguyen, Hanh Thuy
Van Duong, Tu
Taylor, Lynne S.
author_sort Nguyen, Hanh Thuy
collection PubMed
description Recent work has highlighted that amorphous solid dispersions (ASDs) containing delamanid (DLM) and an enteric polymer, hypromellose phthalate (HPMCP), appear to be susceptible to crystallization during immersion in simulated gastric fluids. The goal of this study was to minimize contact of the ASD particles with the acidic media via application of an enteric coating to tablets containing the ASD intermediate, and improve the subsequent drug release at higher pH conditions. DLM ASDs were prepared with HPMCP and formulated into a tablet that was then coated with a methacrylic acid copolymer. Drug release was studied in vitro using a two-stage dissolution test where the pH of the gastric compartment was altered to reflect physiological variations. The medium was subsequently switched to simulated intestinal fluid. The gastric resistance time of the enteric coating was probed over the pH range of 1.6–5.0. The enteric coating was found to be effective at protecting the drug against crystallization in pH conditions where HPMCP was insoluble. Consequently, the variability in drug release following gastric immersion under pH conditions reflecting different prandial states was notably reduced when compared to the reference product. These findings support closer examination of the potential for drug crystallization from ASDs in the gastric environment where acid-insoluble polymers may be less effective as crystallization inhibitors. Further, addition of a protective enteric coating appears to provide a promising remediation strategy to prevent crystallization at low pH environments, and may mitigate variability associated with prandial state that arises due to pH changes.
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spelling pubmed-103908252023-08-02 Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release Nguyen, Hanh Thuy Van Duong, Tu Taylor, Lynne S. Int J Pharm Article Recent work has highlighted that amorphous solid dispersions (ASDs) containing delamanid (DLM) and an enteric polymer, hypromellose phthalate (HPMCP), appear to be susceptible to crystallization during immersion in simulated gastric fluids. The goal of this study was to minimize contact of the ASD particles with the acidic media via application of an enteric coating to tablets containing the ASD intermediate, and improve the subsequent drug release at higher pH conditions. DLM ASDs were prepared with HPMCP and formulated into a tablet that was then coated with a methacrylic acid copolymer. Drug release was studied in vitro using a two-stage dissolution test where the pH of the gastric compartment was altered to reflect physiological variations. The medium was subsequently switched to simulated intestinal fluid. The gastric resistance time of the enteric coating was probed over the pH range of 1.6–5.0. The enteric coating was found to be effective at protecting the drug against crystallization in pH conditions where HPMCP was insoluble. Consequently, the variability in drug release following gastric immersion under pH conditions reflecting different prandial states was notably reduced when compared to the reference product. These findings support closer examination of the potential for drug crystallization from ASDs in the gastric environment where acid-insoluble polymers may be less effective as crystallization inhibitors. Further, addition of a protective enteric coating appears to provide a promising remediation strategy to prevent crystallization at low pH environments, and may mitigate variability associated with prandial state that arises due to pH changes. Elsevier/North-Holland Biomedical Press 2023-07-25 /pmc/articles/PMC10390825/ /pubmed/37311499 http://dx.doi.org/10.1016/j.ijpharm.2023.123139 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nguyen, Hanh Thuy
Van Duong, Tu
Taylor, Lynne S.
Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title_full Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title_fullStr Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title_full_unstemmed Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title_short Enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: A strategy to enhance in vitro release
title_sort enteric coating of tablets containing an amorphous solid dispersion of an enteric polymer and a weakly basic drug: a strategy to enhance in vitro release
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390825/
https://www.ncbi.nlm.nih.gov/pubmed/37311499
http://dx.doi.org/10.1016/j.ijpharm.2023.123139
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