Enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on Eudragit® E

Youngseok Cho; Eun Sol Ha; In Hwan Baek; Min Soo Kim; Cheong Weon Cho; Sung Joo Hwang

doi:10.3390/molecules20069496

Enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on Eudragit® E

Youngseok Cho, Eun Sol Ha, In Hwan Baek, Min Soo Kim, Cheong Weon Cho, Sung Joo Hwang

Department of Pharmacy

Research output: Contribution to journal › Article

11 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	9496-9509
Number of pages	14
Journal	Molecules
Volume	20
Issue number	6
DOIs	https://doi.org/10.3390/molecules20069496
Publication status	Published - 2015 Jun 1

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All Science Journal Classification (ASJC) codes

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

Cite this

Cho, Y., Ha, E. S., Baek, I. H., Kim, M. S., Cho, C. W., & Hwang, S. J. (2015). Enhanced supersaturation and oral absorption of sirolimus using an amorphous solid dispersion based on Eudragit® E. Molecules, 20(6), 9496-9509. https://doi.org/10.3390/molecules20069496

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abstract = "The present study aimed to investigate the effect of Eudragit{\textregistered} 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.",

author = "Youngseok Cho and Ha, {Eun Sol} and Baek, {In Hwan} and Kim, {Min Soo} and Cho, {Cheong Weon} and Hwang, {Sung Joo}",

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