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

Min Soo Kim, Jeong Soo Kim, Hee Jun Park, Won Kyung Cho, Kwang Ho Cha, Sung Joo Hwang

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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 AUC0→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.

Original languageEnglish
Pages (from-to)2997-3009
Number of pages13
JournalInternational journal of nanomedicine
Volume6
DOIs
Publication statusPublished - 2011 Jan 1

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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