Injectable 3-month buprenorphine PLGA microparticle formulation

可注射 3 个月丁丙诺啡 PLGA 微粒制剂

• 批准号: 10682808
• 负责人: Haesun Park
• 金额: $ 32万
• 依托单位: AKINA, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10682808
• 关键词: Buprenorphine; Businesses; Canis familiaris; Clinical; Clinical Research; Data; Development; Drug Kinetics; Esters; Excision; Formulation; Glycolic-Lactic Acid Polyester; Goals; Implant; In Situ; In Vitro; Indiana; Injectable; Injections; Kinetics; Knowledge; Laboratories; Molecular Structure; Molecular Weight; Monitor; Naltrexone; Operative Surgical Procedures; Organic solvent product; Outcome; Pharmaceutical Preparations; Phase; Polymers; Preparation; Price; Process; Property; Rattus; Residual state; Sales; Small Business Innovation Research Grant; Solubility; Solvents; Structure; Technology; Therapeutic; United States Food and Drug Administration; canine model; compliance behavior; cost; crystallinity; dalton; design; in vivo; innovation; manufacture; manufacturing process; manufacturing scale-up; opioid use disorder; particle; patient retention; phase 1 study; phase 2 study

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.

项目摘要 该I期研究的目的是开发一种3个月递送丁丙诺啡制剂，用于治疗 阿片类药物使用障碍（OUD）。开发一种长效注射丁丙诺啡制剂是当务之急 这是治疗OUD所必需的。目前，只有两种1个月丁丙诺啡注射制剂， 和Brixadi®已获得美国食品和药物管理局（FDA）批准。Probuphine®，6个月 丁丙诺啡植入物需要手术放置和移除，于2020年在美国停产。 Akina在过去的十年中积累了制作长效（1~6）的知识和技术， 月）的基于可生物降解的聚（丙交酯-共-乙交酯）（PLGA）的可注射微粒制剂。的 该I期研究的目的是开发3个月可注射的丁丙诺啡PLGA微粒制剂。 具体目的1：制备并表征3个月作用的300 mg丁丙诺啡注射制剂。 具体目标2：确定控制最终配方属性的关键材料和工艺因素。 3个月可注射丁丙诺啡微粒制剂的开发将使用 Akina的技术和诀窍。本研究第一阶段的创新之处在于利用Akina的能力， 用于控制丁丙诺啡释放而没有初始突释的合适的PLGA聚合物和溶剂。 存在不同的PLGA聚合物，其丙交酯：乙交酯（L：G）比率、分子量、分子量和分子量分布不同。 结构和端基。这里的创新是选择L：G比为85：15的PLGA， 重量≤ 100，000道尔顿，线性PLGA结构和酯端基，基于我们对 PLGA性质。与试错法相比，它大大减少了设计空间。 第一阶段研究的成功完成将使我们进入一个有希望的第二阶段研究，其中一个3- 将大规模（约300 g/批）生产一个月制剂，用于体内丁丙诺啡释放 使用老鼠和狗的研究。最终，Akina将推出一种为期3个月的可注射丁丙诺啡制剂 用于临床研究和FDA的批准。