TIMOLOL RELEASE FROM MATRICES OF MONOESTERS OF POLY(VINYL METHYL ETHER-MALEIC ANHYDRIDE) - EFFECTS OF POLYMER MOLECULAR-WEIGHT AND A BASIC ADDITIVE

Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are acidic bioerodible polymers that have been used in cosmetics and tablet film coatings. They may be suitable for topical controlled-release applications since the polymeric backbone is not cleaved to smaller fragments that could be absorbed into the systemic circulation. The dissolution of these polymers depends on the length of the alkyl ester chain of the polymer and on the pH on the polymer surface. We studied the effect of the molecular weight of the polymer on in vitro release of timolol from matrices of n-propyl, n-butyl, and n-hexyl monoesters of PVM-MA. The effect of a basic additive, disodium phosphate, on timolol release from the polymers was also evaluated. The rate of timolol release decreased with increasing length of the alkyl side chain in the polymer. Drug release from the n-propyl and n-butyl monoesters followed zero-order release kinetics, but that from the n-hexyl monoester followed square root-of-time release kinetics. The molecular weight of the polymer did not affect drug release from the matrices without disodium phosphate. With the basic additive, the rate of timolol release increased with increasing molecular weight from the matrices of n-propyl and n-butyl monoesters of PVM-MA, but had only a very small effect on drug release from the n-hexyl monoester. Release of timolol from the n-propyl and n-butyl monoesters was controlled by polymer dissolution and, thus, it was affected by the basic additive in the matrix. Diffusion-controlled drug release from the n-hexyl ester was not affected by disodium phosphate.