CHEMICAL INTERACTIONS BETWEEN DRUGS CONTAINING REACTIVE AMINES WITH HYDROLYZABLE INSOLUBLE BIOPOLYMERS IN AQUEOUS-SOLUTIONS

Chemical reactions between drugs containing reactive amines with hydro lyzable polymers in buffer solutions were investigated. Phenylalkylami nes with increasing nucleophilic reactivity were used as model drugs. Solutions of phenylalkylamines were reacted heterogeneously with repre sentative biodegradable polyanhydride and polyester powders in various pH solutions, and the recovery of the amines from the solutions was d etermined. Poly(sebacic acid), a reactive polyanhydride, reacted by am ide formation with the tested amines and their respective HCl salts wh en exposed to physiologic pH (pH 7.4). However, at pH 5.0 no interacti on occurred. The aromatic polyanhydride, PCPP, and the polyesters base d on lactic acid and caprolactone did react with the amine derivatives at pH 7.4, but at a slower rate. The reaction can be avoided with app ropriate salt derivatives of the amines.