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Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E

The present study aimed to investigate the effect of Eudragit(®) E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were f...

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Autores principales: Cho, Youngseok, Ha, Eun-Sol, Baek, In-Hwan, Kim, Min-Soo, Cho, Cheong-Weon, Hwang, Sung-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272523/
https://www.ncbi.nlm.nih.gov/pubmed/26020699
http://dx.doi.org/10.3390/molecules20069496
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author Cho, Youngseok
Ha, Eun-Sol
Baek, In-Hwan
Kim, Min-Soo
Cho, Cheong-Weon
Hwang, Sung-Joo
author_facet Cho, Youngseok
Ha, Eun-Sol
Baek, In-Hwan
Kim, Min-Soo
Cho, Cheong-Weon
Hwang, Sung-Joo
author_sort Cho, Youngseok
collection PubMed
description The present study aimed to investigate the effect of Eudragit(®) E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.
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spelling pubmed-62725232018-12-31 Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E Cho, Youngseok Ha, Eun-Sol Baek, In-Hwan Kim, Min-Soo Cho, Cheong-Weon Hwang, Sung-Joo Molecules Article The present study aimed to investigate the effect of Eudragit(®) E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications. MDPI 2015-05-25 /pmc/articles/PMC6272523/ /pubmed/26020699 http://dx.doi.org/10.3390/molecules20069496 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cho, Youngseok
Ha, Eun-Sol
Baek, In-Hwan
Kim, Min-Soo
Cho, Cheong-Weon
Hwang, Sung-Joo
Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title_full Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title_fullStr Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title_full_unstemmed Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title_short Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit(®) E
title_sort enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on eudragit(®) e
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272523/
https://www.ncbi.nlm.nih.gov/pubmed/26020699
http://dx.doi.org/10.3390/molecules20069496
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