Injectable 3-month buprenorphine PLGA microparticle formulation

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PROJECT SUMMARY The objective of this Phase I study is to develop a 3-month delivery buprenorphine formulation for treating opioid use disorder (OUD). Developing a long-acting injectable buprenorphine formulation is urgently necessary for treating OUD. Currently, only two 1-month buprenorphine injectable formulations, Sublocade® and Brixadi®, are approved by the U.S. Food and Drug Administration (FDA). Probuphine®, a 6-month buprenorphine implant requiring surgical placement and removal, was discontinued in the U.S. in 2020. Akina has cumulated over the last decade the knowledge and technology for making long-acting (1~6 months) injectable microparticle formulations based on biodegradable poly(lactide-co-glycolide) (PLGA). The goal of this Phase I study is to develop a 3-month injectable buprenorphine PLGA microparticle formulation. Specific Aim 1: To prepare and characterize a 3-month-acting injectable 300 mg buprenorphine formulation. Specific Aim 2: To identify the key material and process factors that control the final formulation's attributes. Development of a 3-month injectable buprenorphine microparticle formulation will be prepared using Akina's technology and know-how. The innovation in this Phase I study is to utilize Akina's ability to select the suitable PLGA polymers and solvents for controlling the buprenorphine release without the initial burst release. There are diverse PLGA polymers differing in their lactide:glycolide (L:G) ratio, molecular weight, molecular structure, and end-group. The innovation here is to select PLGA with the L:G ratio of 85:15, the molecular weight of ≤100,000 Daltons, linear PLGA structure, and ester end-group based on our understanding of the PLGA properties. It drastically reduces the design space over the trial-and-error approach. The successful completion of the Phase I study will bring us into a promising Phase II study, in which a 3- month formulation will be manufactured on a large scale (~300 g/batch) for in vivo buprenorphine release studies using rats and dogs. Ultimately, Akina will introduce a 3-month injectable buprenorphine formulation for clinical studies and the approval by the FDA.