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

Content Provider	Europe PMC
Author	Kim, Min-Soo Kim, Jeong-Soo Park, Hee Jun Cho, Won Kyung Cha, Kwang-Ho Hwang, Sung-Joo
Copyright Year	2011
Abstract	BackgroundThe 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.MethodsFirst, 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.ResultsX-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→12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.ConclusionThe 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.
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	6
PubMed Central reference number	PMC3230567
PubMed reference number	22162657
e-ISSN	11782013
DOI	10.2147/ijn.s26546
Language	English
Publisher	Dove Medical Press
Publisher Date	2011-11-24
Access Restriction	Open
Rights License	This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. © 2011 Kim et al, publisher and licensee Dove Medical Press Ltd.
Subject Keyword	sirolimus solubility bioavailability supercritical antisolvent nanoparticles
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science