Mechanisms of drug release in citrate buffered HPMC matrices

Abstract

Few studies report the effects of alkalizing buffers in HPMC matrices. These agents are incorporated to provide micro-environmental buffering, protection of acid-labile ingredients, or pH-independent release of weak acid drugs. In this study, the influence of sodium citrate on the release kinetics, gel layer formation, internal gel pH and drug release mechanism was investigated in HPMC 2910 and 2208 (Methocel E4M and K4M) matrices containing 10% felbinac 39% HPMC, dextrose and sodium citrate. Matrix dissolution at pH 1.2 and pH 7.5 resulted in complex release profiles. HPMC 2910 matrices exhibited biphasic release, with citrate increasing the immediate release phase (<60min) and reducing the extended release. HPMC 2208 matrices were accelerated, but without the loss of extended release characteristics. Studies of early gel layer formation suggested gel barrier disruption and enhanced liquid penetration. pH modification of the gel layer was transitory (<2h) and corresponded temporally with the immediate release phase. Results suggest that in HPMC 2910 matrices, high initial citrate concentrations within the gel layer suppress particle swelling, interfere with diffusion barrier integrity, but are lost rapidly whereupon drug solubility reduces and the diffusion barrier recovers. These Hofmeister or osmotic-mediated effects are better resisted by the less methoxylated HPMC 2208.