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

BACKGROUND: 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 sol...

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Autores principales: Kim, Min-Soo, Kim, Jeong-Soo, Park, Hee Jun, Cho, Won Kyung, Cha, Kwang-Ho, Hwang, Sung-Joo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230567/
https://www.ncbi.nlm.nih.gov/pubmed/22162657
http://dx.doi.org/10.2147/IJN.S26546
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author Kim, Min-Soo
Kim, Jeong-Soo
Park, Hee Jun
Cho, Won Kyung
Cha, Kwang-Ho
Hwang, Sung-Joo
author_facet Kim, Min-Soo
Kim, Jeong-Soo
Park, Hee Jun
Cho, Won Kyung
Cha, Kwang-Ho
Hwang, Sung-Joo
author_sort Kim, Min-Soo
collection PubMed
description BACKGROUND: 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 AUC(0→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.
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spelling pubmed-32305672011-12-08 Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process Kim, Min-Soo Kim, Jeong-Soo Park, Hee Jun Cho, Won Kyung Cha, Kwang-Ho Hwang, Sung-Joo Int J Nanomedicine Original Research BACKGROUND: 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 AUC(0→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. Dove Medical Press 2011 2011-11-24 /pmc/articles/PMC3230567/ /pubmed/22162657 http://dx.doi.org/10.2147/IJN.S26546 Text en © 2011 Kim et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Kim, Min-Soo
Kim, Jeong-Soo
Park, Hee Jun
Cho, Won Kyung
Cha, Kwang-Ho
Hwang, Sung-Joo
Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230567/
https://www.ncbi.nlm.nih.gov/pubmed/22162657
http://dx.doi.org/10.2147/IJN.S26546
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