PLGA–PEG microspheres of teverelix: influence of polymer type on microsphere characteristics and on teverelix in vitro release

Abstract

Teverelix microspheres were produced by coacervation using a new type of poly(ester-carbonates) made of block copolymers of poly(lactic-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Five different PLGA–PEG copolymers and one PLGA were used. The ‘stability window’ has been determined for all polymers. It varied depending on the molecular weight and the weight percentage of PEG. With increasing core loading (from 9.4 to 34.2%), the microparticle size increased from 10–50 to 5–1000 μm. The core loading did not have any influence on encapsulation yield, which remained above 80%. The influence of polymer type on microsphere characteristics was studied at two different core loadings: 9.4 and 28%. At a low core loading, the nature of the polymer had no influence on microsphere characteristics whereas at 28%, only PLGA–PEG copolymers gave acceptable microparticles in term of particle size. At 28%, the glass transition temperature ( T g) of loaded particles was 1–8 °C higher than the T g of the corresponding polymer. Increasing the core loading increased teverelix release whereas polymer degradation was decreased. All microparticles made of PLGA–PEG copolymers showed a faster release of teverelix than PLGA-based microspheres, whatever the core loading. One PLGA–PEG was selected on the basis of in vitro release rate for further in vivo investigations.