The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersion particles in the optimized formulations were prepared by spray drying. The particles were characterized in vitro and in vivo. The most effective supersaturatable formulation found in the formulation screening process was hydroxypropylmethyl cellulose (HPMC)-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), followed by HPMC-Sucroester. In addition, the supersaturated state generated from HPMC-TPGS and HPMC-Sucroester 15 particles prepared by spray drying significantly improved the oral absorption of sirolimus in rats. Based on the pharmacokinetic parameters and supporting in vitro supersaturated dissolution data, the enhanced supersaturation properties of sirolimus led to enhanced in vivo oral absorption. In addition, the experimental results from the formulation screening used in our study could be useful for enhancing the bioavailability of sirolimus in preformulation and formulation studies.
Bibliographical noteFunding Information:
This work was supported by the Priority Research Centers Program of the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology ( 2009-0093815 ), and by a grant from the Korea Healthcare Technology R&D Project of the Ministry for Health, Welfare and Family Affairs in the Republic of Korea ( A080470 ).
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science