PARENTERAL DEPOT-SYSTEMS ON THE BASIS OF BIODEGRADABLE POLYESTERS

Parenteral depot systems such as implants and microspheres from biodegradable polyesters have shown deviations from an ideal infusion-like profile. Although the origins of this biphasic behavior are still being discussed controversially, it seems that two release mechanisms from biodegradable parenteral depot systems have to be taken into account namely: pore-diffusion and matrix erosion. To overcome the problem of biphasic release profiles we have synthesized novel biodegradable terpolymers from various core-molecules by grafting PLG on appropriate functionalities. These polymers have physico-chemical and degradation properties differing from linear PLG. Using these terpolymers we obtained bromocriptine microspheres which did not show biphasic release profiles in vivo. The PLG-GLU was used for the development of a parenteral depot formulation of Parlodel(R) on the basis of microspheres. Data on biodegradation and tissue compatibility were generated. Results from ongoing clinical studies will be discussed.