Controlled release of a luteinizing hormone-releasing hormone analogue from poly(d,l-lactide-co-glycolide) microspheres.

The performance in vivo of nafarelin acetate, a potent analogue of luteinizing hormone-releasing hormone, microencapsulated in poly(d,l-lactide-co-glycolide), was evaluated. The influence of polymer composition and molecular weight on the estrus-suppressing activity of the microspheres in female rats was determined. Compound release was shown to be effected by polymer erosion rather than by diffusion. A triphasic release of compound was observed, which was adjusted by altering the critical parameters of the polymer. A mechanism for the release of the compound was proposed. The primary release phase was compound loss by diffusion from the surface of the microspheres. The secondary phase of subeffective rates of release occurred concomitantly with polymer hydrolysis and a decrease in its molecular weight, although it remained insoluble. Dissolution of low-molecular weight fragments and erosion of the bulk of the polymer then initiated the tertiary phase of release of compound.