Enhanced solubility and oral absorption of sirolimus using D-α-tocopheryl polyethylene glycol succinate micelles

Abstract

The objective of this study was to develop an oral formulation that would improve the solubility and oral absorption of sirolimus using a TPGS micellar solution. The effect of TPGS on the solubility and stability of sirolimus was evaluated. The sirolimus-loaded TPGS micelles were prepared using the thin-film hydration method. The average size of the sirolimus-loaded TPGS micelles was 11 nm. The concentration of sirolimus in a 50 mg/mL TPGS micellar solution was 0.97 ± 0.12 mg/mL, which demonstrates an enhancement of approximately 400-fold from the solubility of sirolimus in water. Furthermore, pharmacokinetic studies in rats indicated that the TPGS micellar solution significantly improved the oral absorption of sirolimus. Therefore, the preliminary results from this study suggest that a TPGS micellar solution has great potential for clinical applications.

Keywords::

• Bioavailability
• micelle
• sirolimus
• stability
• TPGS