Effect of chloride on the release of chlorhexidine salts from methyl methacrylate: 2-hydroxyethyl methacrylate copolymer reservoir devices

Abstract

Syntheses of copolymers of methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA) were carried out in solution without the addition of external covalent crosslinkers. Devices were formulated as coated matrices: 80% (w/w) chlorhexidine diacetate was incorporated in a core of 50:50 mole ratio HEMA:MMA copolymer and this matrix was then coated with 30:70 mole ratio HEMA:MMA copolymer. Coated devices released chlorhexidine into water for months with zero-order kinetics. In an inorganic saliva simulate, release rates were significantly lower than those observed from devices into water. Release rates were decreased 36% and 85% in 2.2 mM and 10 mM sodium chloride solutions, respectively. Hydration, pH, and osmotic effects were minimal. The effect of external chloride on the release rates was due to the conversion within the core of the acetate salt of chlorhexidine (solubility ~ 23 mg/ml at 37 °C) to the chloride salt (solubility ~ 1 mg/ml at 37 °C) and the consequent lower solubility. Addition of sodium chloride to a core formulation of chlorhexidine diacetate also resulted in lower release rates and presents as a facile method for release rate adjustment. For external chloride to diffuse into the core requires bulk water in the polymers for chloride transport. Differential scanning calorimetric studies indicated that each of the copolymers contained a significant amount of bulk water and hence a pathway for chloride transport from the external environment into the device core.