Long-Acting injectable buprenorphine PLGA microparticle formulation

Opioid use disorder (OUD) continues to be a major cause of morbidity and mortality globally. Medications for opioid use disorder have shown promise in reducing the illicit use of opioids, resulting in reduced overdose deaths and healthcare costs. Buprenorphine is a widely used drug for treating OUD with attributes favorable for long-acting formulations. The goal of this study was to develop a 3-month long-acting injectable buprenorphine microparticle formulation for treating OUD. The target product profile of the buprenorphine formulation consisted of a loading of 35-40 % and in vivo drug release for ≥3 months. To achieve this goal, we utilized a solid-in-oil-in-water (S/O/W) emulsion technique and defined the critical material attributes of PLGA (85:15, MW = 108 kDa) at 15.2 % w/v in oil phase and critical processing parameters including the use of ethyl acetate as the oil phase solvent and post-particle formation treatment using a 25 % ethanolic solution for 8 h. A pharmacokinetic (PK) study in the rat model shows that the buprenorphine concentration was ≥ 2 ng/mL for over 60 days and then ≥ 1 ng/mL for another 40 days, maintaining the buprenorphine concentration above 1 ng/mL; equivalent to the levels observed in other commercially available formulations for a longer-release time. Our study has shown the feasibility of making long-acting PLGA microparticles for buprenorphine release for ≥3 months using the S/O/W emulsion method.