Synthesis of medical grade PLLA, PDLLA, and PLGA by a reactive extrusion polymerisation

Abstract Due to their biodegradability and biocompatibility, aliphatic polyesters received a considerable attention for a wide range of applications, in particular in medical and pharmaceutical fields. Aliphatic polyesters are usually synthesized by ring opening polymerization in a batch mode. In this work, a reactive extrusion polymerization was optimized to synthesize in a continuous way poly-L-lactide, poly-D,L-lactide, and poly-D,L-lactide-co-glycolide 50:50. A lab scale co-rotating twin screw extruder adapted for pharmaceutical products and medical devices was used after optimizing the geometry of screws and barrel. Polymerization was conducted in the presence of tin (II) 2-ethylhexanoate as catalyst and a monohydroxylated polyethylene glycol as initiator. The optimized procedure allowed producing high molecular weight polyesters (Mn in the range [15-100 kDa]) in a controlled way on a time scale of some minutes, with a capacity of at least 100 g/h and with monomer residues lower than 5 %. Comparison of macromolecular features and thermal properties of the resulting polyesters of different Mn with those prepared in a batch process allowed concluding to the similarity of these materials. Reactive extrusion polymerization represents therefore a very attractive methodology to produce in a continuous, rapid and robust way aliphatic polyesters suitable for a wide range of pharmaceutical, medical or nowadays applications.