Effect of macromer molecular weight on in vitro ophthalmic drug release from photo-crosslinked matrices

Abstract

The objective of this study was to investigate the effect of poly(propylene fumarate) (PPF) molecular weight on the release kinetics of two ophthalmic model drugs, acetazolamide (AZ) and timolol maleate (TM), from matrices prepared by photo-induced copolymerization of PPF with N-vinyl pyrrolidone (NVP). PPF macromers of different number average molecular weight ( M n) and polydispersity index (PI) were used in the experiments. Photo-crosslinked matrices were loaded with 5 wt.% AZ or TM. The amounts of released drug and NVP were determined using high-performance liquid chromatography (HPLC). The release kinetics of both drugs was influenced by the molecular weight of the constituent PPF macromer. An increased M n led to an increased burst release and an accelerated drug release. Dependent on the PPF M n, the initial AZ loading was released within periods ranging from 35 days ( M n = 3670, PI = 1.9) to 220 days ( M n = 2050, PI = 1.5). TM-loaded matrices revealed similar release kinetics dependent on the PPF M n. The amount of released NVP from photo-crosslinked matrices during the course of a release experiment was independent of the PPF M n for both drugs. Matrix swelling and erosion were determined gravimetrically. The network structures of non-loaded matrices were further characterized by determining their crosslinking densities and the relative double bond conversions of fumaric acid (FAA) and NVP. Independent of PPF M n, PPF and NVP similarly participated in the formation of the PPF/polyNVP copolymer network. The observed differences in drug release might therefore be explained by differences in the microstructural organization of the copolymer networks. Overall, the results demonstrate that drug release kinetics from photo-crosslinked PPF/polyNVP matrices is strongly dependent on the M n of the PPF macromer.