Drug release from and sterilization of in situ cubic phase forming monoglyceride drug delivery systems

作者：Ahmed Abid Riaz^*; Dashevsky Andrei; Bodmeier Roland

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2010, 75(3): 375-380.

DOI：10.1016/j.ejpb.2010.04.004

• Controlled drug release
• In situ cubic phase
• Monoglyceride
• Oligonucleotide
• Sterilization

Since a monoglyceride-based cubic phase is too viscous to be injected parenterally, mixtures of monoglyceride, water and water-miscible cosolvents were investigated as low viscosity injectable in situ cubic phase-forming formulations. Upon contact with the release medium, a highly viscous cubic phase formed rapidly and served as an extended release matrix for the oligonucleotide drug. Extended drug release was obtained with all formulations. The drug release followed the square root of time relationship indicating a diffusion-controlled release mechanism. The release depended on the type of cosolvent and followed the order of ethanol > PEG 300 > 2-pyrrolidone > DMSO. Higher water or monoglycerides contents decreased the drug release because of an increased viscosity and increased swollen matrix thickness. The bioburden of different commercially available monoglycerides and of the prepared in situ cubic phase-forming formulations met USP XXIII requirements. Monoglycerides can be successfully sterilized by gamma irradiation or by autoclaving and the in situ cubic phase-forming formulations by autoclaving and aseptic filtration. The monoglycerides and in situ cubic phase-forming formulations retained their phase behaviour and release properties after sterilization.

• 出版日期2010-8