Evaluation of the stability and absorption of tacrolimus self-microemulsifying drug delivery system

Tacrolimus (FK506) is one of the most usually used drugs for organ transplantation. The poor bioavailability of FK506 is mainly caused by its low solubility, which can be improved by the application of self-microemulsifying drug delivery system (SMEDDS). This study was focused on the evaluation of the stability of size and drug content, and in vivo absorption of the FK506-SMEDDS. The droplet size of the emulsion formed by the SMEDDS was not affected by the pH of media. Dilution of the emulsion caused slight increase of size but the content of FK506 was maintained. The FK506 in the SMEDDS was not stable under high temperature, high humidity or strong light irradiation but it was prevented by the addition of 0.25% citric acid into the SMEDDS. The blank SMEDDS did not show negative effect on the viability of Caco-2 cells. In the single pass intestinal perfusion test, the intestinal absorption of FK506 was improved by the SMEDDS but the commercial product Prograf® best enhanced the drug absorption. The pharmacokinetic study revealed that the relative bioavailability of FK506-SMEDDS was 134.97% to the Prograf®. In conclusion, the FK506-SMEDDS presented as a promising oral delivery system with favorable stability and in vivo absorption.