Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process

Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground...

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Autores principales:	Kim MS, Kim JS, Park HJ, Cho WK, Cha KH, Hwang SJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/114c0d285ccb46c38553ebc258d03531
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spelling	oai:doaj.org-article:114c0d285ccb46c38553ebc258d035312021-12-02T07:36:59ZEnhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process1176-91141178-2013https://doaj.org/article/114c0d285ccb46c38553ebc258d035312011-11-01T00:00:00Zhttp://www.dovepress.com/enhanced-bioavailability-of-sirolimus-via-preparation-of-solid-dispers-a8733https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats.Results: X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0&rarr;12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.Conclusion: The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus.Keywords: sirolimus, solubility, bioavailability, supercritical antisolvent, nanoparticlesKim MSKim JSPark HJCho WKCha KHHwang SJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2997-3009 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Kim MS Kim JS Park HJ Cho WK Cha KH Hwang SJ Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
description	Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats.Results: X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0&rarr;12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.Conclusion: The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus.Keywords: sirolimus, solubility, bioavailability, supercritical antisolvent, nanoparticles
format	article
author	Kim MS Kim JS Park HJ Cho WK Cha KH Hwang SJ
author_facet	Kim MS Kim JS Park HJ Cho WK Cha KH Hwang SJ
author_sort	Kim MS
title	Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title_short	Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title_full	Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title_fullStr	Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title_full_unstemmed	Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title_sort	enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/114c0d285ccb46c38553ebc258d03531
work_keys_str_mv	AT kimms enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess AT kimjs enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess AT parkhj enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess AT chowk enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess AT chakh enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess AT hwangsj enhancedbioavailabilityofsirolimusviapreparationofsoliddispersionnanoparticlesusingasupercriticalantisolventprocess
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Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process

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