Poly (glycolic acid-co- dl-lactic acid): diffusion or degradation controlled drug delivery?

Abstract

The mechanism of release of drugs from poly(glycolic acid-co- dl-lactic acid), PGLA, was reinvestigated. Films of a 1:1 copolymer were either solvent-cast or prepared by compression of micronized powders. The water content, glass transition temperature, hydrolytic chain scission, and weight loss of PGLA were measured as a function of time in deionized (DI) water and phosphate-buffered saline (PBS), pH 7.4, at 37°C. Changes in these properties were compared with the rates of release of testosterone and bovine serum albumin (BSA) from PGLA films in order to establish their contribution to the delivery mechanism. Rates of release were initially slow, but exhibited a characteristic acceleration between 10 and 15 days. The rates were largely independent of the medium, DI-water or PBS, and the method of device fabrication. There was no correlation of the change in drug release kinetics with the glass transition temperature, which in water decreased from 45°C (dry state) to 30°C within 1 h and to 10°C after 2 weeks. The water content of PGLA increased with time and depended on the medium; values greater than 20% were the result of pores formed by polymer dissolution within the polymer bulk. The decrease in the molecular weight with time exhibited the semi-logarithmic relationship characteristic of the hydrolytic chain scission of other aliphatic polyesters. Polymer weight loss was not observed until the M n had decreased to several hundred, and coincided with the onset of more rapid drug release. Microscopy suggested that polymer weight loss was a bulk process. This was confirmed by the rate of drug release, which was identical to the rate of polymer weight loss but independent of its surface-to-volume ratio.