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

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 synthesise 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.