Pilocarpine release from matrices of alkyl half-esters of poly(vinyl methyl ether/maleic anhydride)

Abstract

Alkyl half-esters of poly(vinyl methyl ether/maleic anhydride) (PVM/MA) have been suggested as possible matrix polymers for the erosion-controlled delivery of highly water-soluble drugs. Ethyl, propyl and butyl half-esters of PVM/MA were synthetized and solvent cast with and without a water-soluble drug, pilocarpine hydrochloride. Dissolution of the polymers and release of pilocarpine from the matrices were studied in 1.3 mM and in 66.7 mM phosphate buffers with initial pH of 7.4. Pilocarpine release and polymer dissolution were faster from matrices of ethyl half-esters than from propyl and butyl half-esters of PVM/MA, which were in this respect similar. The only exception was that pilocarpine was released faster from propyi than from butyl half-ester of PVM/MA in 1.3 mM phosphate buffer. The half-esters were dissolved from the matrices at a slower proportional rate than pilocarpine was. This caused a decrease in the drug concentration of the undissolved matrix portion. Pilocarpine was released at a constant rate from butyl half-ester matrices; but from ethyl and propyl half-esters, pilocarpine was released at decreasing rates. In drug release from half-ester matrices, diffusional leaching was significantly increased with increasing hydrophilicity of the matrix and decreasing size of the alkyl ester group. The constant rate of drug release from butyl half-ester matrices was probably due to Case II transport, i.e. drug release was controlled by the constant rate of solvent-induced polymer relaxations in the matrices. The rates of pilocarpine release and polymer dissolution were decreased by diminishing the concentration of phosphate buffer. At the same time diffusional leaching was increased.