Development of a Novel Oral Micellar Formulation of Propofol

摘要

Propofol is a poorly soluble liquid anaesthetic drug available commercially as an emulsion for iv administration (Diprivan® Baxter Inc). Propofol has also been shown to display efficacy in the amelioration of intractable migraine and as a potential treatment for nausea and vomiting, indications for which liquid emulsions are not well suited. Here we describe the development of a solid formulation of propofol for oral administration that uses novel micellar technology to improve oral bioavailability. We first describe the formulation of propofol within polymeric micelles (PM) comprising amphiphilic block copolymers and go on to describe the preparation of a solid spray dried preparation suitable for compression or capsule filling. We report the ability of the micellar formulation to enable translocation of propofol across Caco-2 monolayers in vitro and present in vivo data demonstrating the enhanced oral bioavailability of propofol achieved by the formulation.