Enhanced Bioavailability of Sirolimus Via Preparation of Solid Dispersion Nanoparticles Using a Supercritical Antisolvent Process

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2011 Dec 14

PMID 22162657

Citations 37

Authors

Min-Soo Kim

Jeong-Soo Kim

Hee Jun Park

Won Kyung Cho

Kwang-Ho Cha

Sung-Joo Hwang

Affiliations

Soon will be listed here.

Abstract

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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