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

Research output: Contribution to journalArticle

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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 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.

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

Fingerprint

Sirolimus
Nanoparticles
Biological Availability
Povidone
Sodium dodecyl sulfate
Rats
Dissolution
Surface active agents
Solubility
High pressure liquid chromatography
Surface-Active Agents
Sodium Dodecyl Sulfate
Pharmacokinetics
Supersaturation
Glycols
Dispersions
Propylene
Differential scanning calorimetry
Propylene Glycol
Particle size

All Science Journal Classification (ASJC) codes

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

Cite this

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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 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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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.

In: International journal of nanomedicine, Vol. 6, 01.01.2011, p. 2997-3009.

Research output: Contribution to journalArticle

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AU - Kim, Jeong Soo

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AU - Cho, Won Kyung

AU - Cha, Kwang Ho

AU - Hwang, Sung Joo

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