Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems

A new class of surfactants with glycerate headgroups, that form viscous lyotropic liquid crystalline phases in excess water, have been investigated for their potential to provide sustained release matrices for depot drug delivery. Oleyl glycerate and phytanyl glycerate were used as representative surfactants of this new class, and their behaviour compared with that of glyceryl monooleate (GMO). The surfactants were found to form reverse hexagonal phase (H-Iota Iota) in excess water, and the matrices were loaded with a series of model hydrophobic and hydrophilic drugs, (paclitaxel, irinotecan, glucose, histidine and octreotide), and the release kinetics determined. In all cases, the release behaviour obeyed Higuchi kinetics, with linear drug release versus square root of time. The H-Iota Iota phases released model drugs slower than the GMO cubic phase matrix. The oleyl glycerate matrix was found to consistently release drug faster than the phytanyl glycerate matrix, despite both matrices being based on H-Iota Iota phase. To further demonstrate the potential utility of these materials as drug depot delivery systems, an injectable precursor formulation for octreotide was also prepared and demonstrated to provide controlled release for the peptide. The stability of the H-Iota Iota phase to likely in vivo breakdown products was also assessed. (c) 2005 Elsevier B.V. All rights reserved.