EFFECT OF CHLORIDE ON THE RELEASE OF CHLORHEXIDINE SALTS FROM METHYL-METHACRYLATE - 2-HYDROXYETHYL METHACRYLATE COPOLYMER RESERVOIR DEVICES

Syntheses of copolymers of methyl methacrylate (MMA) and 2-hydroxyethy l methacrylate (HEMA) were carried out in solution without the additio n of external covalent crosslinkers. Devices were formulated as coated matrices: 80% (w/w) chlorhexidine diacetate was incorporated in a cor e of 50:50 mole ratio HEMA:MMA copolymer and this matrix was then coat ed with 30:70 mole ratio HEMA:MMA copolymer. Coated devices released c hlorhexidine into water for months with zero-order kinetics. In an ino rganic saliva simulate, release rates were significantly lower than th ose 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 externa l chloride on the release rates was due to the conversion within the c ore of the acetate salt of chlorhexidine (solubility similar to 23 mg/ ml at 37 degrees C) to the chloride salt (solubility similar to 1 mg/m l at 37 degrees C) and the consequent lower solubility. Addition of so dium chloride to a core formulation of chlorhexidine diacetate also re sulted in lower release rates and presents as a facile method for rele ase rate adjustment. For external chloride to diffuse into the core re quires bulk water in the polymers for chloride transport. Differential scanning calorimetric studies indicated that each of the copolymers c ontained a significant amount of bulk water and hence a pathway for ch loride transport from the external environment into the device core.