Development of a Solid Supersaturatable Self-Emulsifying Drug Delivery System of Docetaxel with Improved Dissolution and Bioavailability

作者：Chen, Ying^*; Chen, Chen; Zheng, Jianling; Chen, Zhiyu; Shi, Qiongzhi; Liu, Hong

来源：Biological & Pharmaceutical Bulletin, 2011, 34(2): 278-286.

DOI：10.1248/bpb.34.278

• docetaxel
• self-emulsifying drug delivery system
• supersaturation promoter
• solid dosage form
• dissolution in vitro
• bioavailability

The objective of this study was to prepare a solid supersaturatable self-emulsifying drug delivery system (S-sSEDDS) using docetaxel (DTX). Different from conventional self-emulsifying drug delivery systems (SEDDSs), a solid supersaturatable self-emulsifying drug delivery system of docetaxel (DTX-S-sSEDDS) was prepared by spray drying, using lactose as the solid carrier and hydroxypropyl methylcellulose (HPMC) as the supersaturation promoter. Physicochemical properties and in vitro dissolution was observed while taking into account factors such as formulations, supersaturated promoters, solid carriers, and preparation methods. The bioavailability of the DTX-S-sSEDDS(1) compared with other formulations of DTX was evaluated in rats. The results showed that the presence of HPMC effectively sustained the supersaturated state by retarding the precipitation kinetics. Although the total amount of emulsifying excipients in the DTX-S-sSEDDS(1) was only 3/5 as much as that of the conventional SEDDS (DTX-SEDDS2), the percent of the accumulated dissolved DTX-S-sSEDDS(1) at 2 h reached 90.96%, which was higher than that of the DTX-SEDDS2 (76.26%) and approximately 29.8 times as much as that of the DTX crude powder. The in vivo studies indicated that the area under the concentration time curve (AUC(0-infinity)) of the DTX-S-sSEDDS(1) increased by nearly 8.77-fold, 1.45-fold more than those of the DTX powder and the conventional SEDDS without the presence of HPMC (DTX-SEDDS1) at a dose of 10 mg/kg. In conclusion, the S-sSEDDS provides an effective approach for improving the dissolution and bioavailability of docetaxel with a low level of emulsifying excipients and provides a reference for good stabilization and the safety of SEDDSs.

• 出版日期2011-2
• 单位中国人民解放军广州军区武汉总医院