Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system

oved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system Original Research (3620) Total Article Views Authors: Chen ZQ, Liu Y, Zhao JH, Wang L, Feng NP Published Date February 2012 Volume 2012:7 Pages 1115 - 1125 DOI: http://dx.doi.org/10.2147/IJN.S28761 Received: 01 December 2011 Accepted: 05 January 2012 Published: 23 February 2012 Zhi-Qiang Chen, Ying Liu, Ji-Hui Zhao, Lan Wang, Nian-Ping Feng School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China Background: Indirubin, isolated from the leaves of the Chinese herb Isatis tinctoria L, is a protein kinase inhibitor and promising antitumor agent. However, the poor water solubility of indirubin has limited its application. In this study, a supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) was developed to improve the oral bioavailability of indirubin. Methods: A prototype S-SMEDDS was designed using solubility studies and phase diagram construction. Precipitation inhibitors were selected from hydrophilic polymers according to their crystallization-inhibiting capacity through in vitro precipitation tests. In vitro release of indirubin from S-SMEDDS was examined to investigate its likely release behavior in vivo. The in vivo bioavailability of indirubin from S-SMEDDS and from SMEDDS was compared in rats. Results: The prototype formulation of S-SMEDDS comprised Maisine 35-1:Cremophor EL:Transcutol P (15:40:45, w/w/w). Polyvinylpyrrolidone K17, a hydrophilic polymer, was used as a precipitation inhibitor based on its better crystallization-inhibiting capacity compared with polyethylene glycol 4000 and hydroxypropyl methylcellulose. In vitro release analysis showed more rapid drug release from S-SMEDDS than from SMEDDS. In vivo bioavailability analysis in rats indicated that improved oral absorption was achieved and that the relative bioavailability of S-SMEDDS was 129.5% compared with SMEDDS. Conclusion: The novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of indirubin in rats. The results suggest that S-SMEDDS is a superior means of oral delivery of indirubin.