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Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility

The formulation of arylpropionic acid derivatives (profens), which are poorly soluble Biopharmaceutical Classification System (BCS) Type II drugs, has a strong impact on their therapeutic action. This article shows that heat-treated powder mixtures of free acid profens with high surface area Cladoph...

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Autores principales: Mantas, Athanasios, Labbe, Valentine, Loryan, Irena, Mihranyan, Albert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409705/
https://www.ncbi.nlm.nih.gov/pubmed/30736357
http://dx.doi.org/10.3390/pharmaceutics11020068
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author Mantas, Athanasios
Labbe, Valentine
Loryan, Irena
Mihranyan, Albert
author_facet Mantas, Athanasios
Labbe, Valentine
Loryan, Irena
Mihranyan, Albert
author_sort Mantas, Athanasios
collection PubMed
description The formulation of arylpropionic acid derivatives (profens), which are poorly soluble Biopharmaceutical Classification System (BCS) Type II drugs, has a strong impact on their therapeutic action. This article shows that heat-treated powder mixtures of free acid profens with high surface area Cladophora cellulose induces drug amorphization and results in enhanced solubility and bioavailability. Similar mixtures produced using conventional low surface area cellulose, i.e., microcrystalline cellulose, does not produce the same effect. The concept is thoroughly described and links the solid-state characterization data, such as differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infra-red spectroscopy, with in vitro dissolution in biorelevant media and in vivo pharmacokinetic analysis in rats. The concept is demonstrated for several substances from the profens group, including ibuprofen (main model drug), ketoprofen, flurbiprofen, and naproxen. The presented approach opens new ways to produce solid dosage forms of profen drugs in their free acidic form as alternatives to existing analogues, e.g., drug-salt conjugates or soft gel liquid capsules.
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spelling pubmed-64097052019-03-29 Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility Mantas, Athanasios Labbe, Valentine Loryan, Irena Mihranyan, Albert Pharmaceutics Article The formulation of arylpropionic acid derivatives (profens), which are poorly soluble Biopharmaceutical Classification System (BCS) Type II drugs, has a strong impact on their therapeutic action. This article shows that heat-treated powder mixtures of free acid profens with high surface area Cladophora cellulose induces drug amorphization and results in enhanced solubility and bioavailability. Similar mixtures produced using conventional low surface area cellulose, i.e., microcrystalline cellulose, does not produce the same effect. The concept is thoroughly described and links the solid-state characterization data, such as differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infra-red spectroscopy, with in vitro dissolution in biorelevant media and in vivo pharmacokinetic analysis in rats. The concept is demonstrated for several substances from the profens group, including ibuprofen (main model drug), ketoprofen, flurbiprofen, and naproxen. The presented approach opens new ways to produce solid dosage forms of profen drugs in their free acidic form as alternatives to existing analogues, e.g., drug-salt conjugates or soft gel liquid capsules. MDPI 2019-02-06 /pmc/articles/PMC6409705/ /pubmed/30736357 http://dx.doi.org/10.3390/pharmaceutics11020068 Text en © 2019 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
Mantas, Athanasios
Labbe, Valentine
Loryan, Irena
Mihranyan, Albert
Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title_full Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title_fullStr Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title_full_unstemmed Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title_short Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
title_sort amorphisation of free acid ibuprofen and other profens in mixtures with nanocellulose: dry powder formulation strategy for enhanced solubility
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409705/
https://www.ncbi.nlm.nih.gov/pubmed/30736357
http://dx.doi.org/10.3390/pharmaceutics11020068
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