Effect of dissolution media and additives on the drug release from cubic phase delivery systems

Abstract

Unsaturated monoglycerides such as monooleate or monolinoleate form a physically stable, highly viscous cubic phase in contact with excess aqueous medium. The swelling and release properties of drug-loaded monoglyceride matrices were evaluated with regard to the development of an oral sustained release delivery system. The swelling capacity of the amphiphilic monoglyceride matrix was higher in 0.1 M pH 7.4 phosphate buffer than in 0.1 N HCl. However, the drug release was opposite in trend, with propranolol HCl being released at a slower rate in pH 7.4 buffer. This was attributed to the presence of free fatty acids in the monoglyceride matrix, which were ionized at pH 7.4, but unionized in 0.1 N HCl. The formation of insoluble complexes with the cationic drug, propranolol HCl, at the higher pH explained the slower release. The incorporation of oleic acid in the monoglyceride matrices further confirmed the influence of fatty acids and was a tool to manipulate the release of cationic drugs. The inclusion of oleic acid and propranolol HCl resulted in the concentration- and pH-dependent formation of other mesophases besides the cubic phase. Varying the ionic strength of the dissolution medium had a minor effect on both swelling and drug release from the nonionic, amphiphilic monoglycerides. While the cubic phase stayed physically intact in enzyme-free simulated gastrointestinal fluids, the addition of bile salts to the pH 7.4 buffer resulted in the dispersion and disappearance of the swollen monoglyceride phase.