In vitro controlled release kinetics of local anaesthetics from poly(D, L-lactide) and poly(lactide-co-glycolide) microspheres

Poly(D, L)lactide and polylactide-co-glycolide drug-loaded microspheres were prepared with lipophilic (bupivacaine and etidocaine) and hydrophilic (mepivacaine and lidocaine) local anaesthetics. Formulations of drug-loaded microspheres were characterized by the drug content, the in-vitro release kinetics and by the physical state of the drug within the microspheres. Release rates of the local anaesthetics from the microspheres were different and could not be accounted for by the intrinsic dissolution rates of the drugs. The encapsulation efficiency was highly dependent on the lipophilicity of the drugs, reaching the maximum for the lipophilic drugs and the poly(lactide-co-glycolide) polymers. The influence of the molecular weight of the poly(lactide-co-glycolide) polymers on the release rate and on the release mechanism depended on the drug studied and its physical state within the polymeric matrices. Diffusion-controlled release was evidenced in various formulations as a result of the linearity of the release as a function of the square root of time.