Buprenorphine loaded PLGA microparticles: Characterization of a sustained-release formulation

Abstract

Buprenorphine is a short-acting analgesic drug. Its use in veterinary medicine requires several injections per day to alleviate pain in animals. We, therefore, designed a poly-lactic-co-glycolic acid (PLGA) based depot formulation of the opioid to prolong the analgesic effect. We characterized our novel microparticulate depot formulation with emphasis on a potential future product development in the present work.Microparticles showed low residual moisture levels and did meet bacterial endotoxin requirements defined by the European Pharmacopeia. Depot formulation showed physicochemical stability over 6 months at 4 °C, indicating sufficient shelf life. Reconstituted formulation stored at 4 °C showed unchanged release properties for 24 h. Terminal sterilization by x-rays with a dose of 30 kGy revealed the sensitivity of buprenorphine towards radiation, resulting in substantial drug degradation. However, microparticle properties were not affected. Our experiments indicate that sterilization of the final product is not possible, therefore requiring aseptic manufacturing protocols.In conclusion, our novel buprenorphine depot formulation based on PLGA microparticles can be stored for at least 6 month as a lyophilisate and can be used for at least 24 h after reconstitution. Pilot experiments suggest that scale-up and a future aseptic production should be feasible. We conclude that the novel depot formulation shows promising attributes, a prerequisite for future industrial production and commercialization.