Expanding Precision Particle Fabrication Technology for the Widespread Control of

扩展精密粒子制造技术以实现广泛控制

• 批准号: 8589942
• 负责人: Nathan H Dormer
• 金额: $ 56.76万
• 依托单位: ORBIS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8589942
• 关键词: Address; Biological Availability; Caliber; Characteristics; Chemicals; Clinical; Collection; Complement; Cyclic GMP; Development; Devices; Drug Delivery Systems; Drug Formulations; Drug Industry; Eating; Elements; Engineering; Equipment; Funding; Future; Goals; Grant; Heating; Ibuprofen; Individual; Investments; Licensing; Liquid substance; Manuals; Marketing; Mechanics; Mediating; Methods; Metric; Microspheres; Modeling; Monitor; Oral; Outcome; Particle Size; Performance; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Process; Production; Research; Shapes; Site; Small Business Innovation Research Grant; Staging; Suspension substance; Suspensions; System; Tars; Techniques; Technology; Temperature; Testing; Touch sensation; Variant; Water; clinical efficacy; compliance behavior; controlled release; cost; cost effective; design; dosage; drug market; drug production; flexibility; graphical user interface; improved; in vivo; industry partner; innovation; meetings; melting; novel; particle; preference; pressure; programs; prototype; public health relevance; research and development; scale up; water solubility

DESCRIPTION (provided by applicant): A critical need currently exists in the pharmaceutical market for microparticles that can accurately and effectively control the release of poorly water-soluble compounds. Although these poorly water-soluble drugs are projected to have high clinical efficacy, they are often rejected in the early stages of research because of the high cost and technical difficulties of formulating and delivering molecules with poor water-solubility. Orbis Biosciences' novel Precision Particle Fabrication (PPF) technology has the potential to address this drug formulation dilemma by allowing flexible, cost-effective, single-step encapsulation of poorly water- soluble drugs, while also providing precise control over particle size, shape, composition, and release profiles. Our long-term goal is the application of a commercial-scale multi-nozzle PPF system for the production of drug-loaded particles with precisely engineered physical characteristics. Under SBIR Phase I Lab-to-Marketplace funding, we designed and optimized a multi-nozzle unit consisting of 12 individual nozzles capable of producing uniform, poorly water-soluble drug-containing microparticles of defined size and release characteristics. With this multi-nozzle unit design, we succeeded in our Phase I goal of establishing the feasibility of improving PPF production rate for encapsulation of poorly soluble drugs. The objective of this SBIR Phase II proposal is to incorporate 4 of these multi-nozzle units into a cGMP-ready, electronically controlled and monitored PPF processing device that will be capable of producing homogenously distributed 100 mm microparticles at a pilot scale production rate of 1 kg/hr and will be compatible with poorly water-soluble drugs. We will design, assemble, and fully test the mechanical subsystems of this PPF system (Aim 1). In parallel, we will also design, assemble, and test a fully integrated electrical system with a graphical user interface (GUI) that will control the mechanical subsystems and regulate key process parameters, including critical temperatures and pressures (Aim 2). Finally, we will integrate the mechanical and electrical components and optimize the system to achieve target performance metrics and particle specifications (Aim 3). Development of such a system will demonstrate the feasibility of scaling the multi-nozzle PPF system for full commercial scale production and derisk outside investment in the technology thereby enabling companies to partner in the co-development of PPF-enabled products. This proposal lays the groundwork for a platform to produce aseptic (but non-sterile) drug intermediates with release rates determined by the design of the microparticles themselves, not the final dosage format; thus, they may be processed into a variety of oral delivery formats without altering the drug release characteristics. This enables large degree of format flexibility in the development of pharmaceutical products - minimizing development costs and improving patient compliance.

描述（由申请人提供）：目前医药市场迫切需要能够准确有效地控制水溶性差的化合物释放的微粒。尽管这些水溶性差的药物预计具有较高的临床疗效，但由于成本高昂，它们在研究的早期阶段经常被拒绝 以及配制和递送水溶性差的分子的技术困难。 Orbis Biosciences 的新型精密颗粒制造 (PPF) 技术有潜力解决这一药物配方难题，它允许灵活、经济高效、一步封装水溶性差的药物，同时还提供对颗粒大小、形状、成分和释放曲线的精确控制。我们的长期目标是应用商业规模的多喷嘴 PPF 系统来生产具有精确设计的物理特性的载药颗粒。 在 SBIR 第一阶段实验室到市场资助下，我们设计并优化了一个多喷嘴装置，该装置由 12 个单独的喷嘴组成，能够生产具有规定尺寸和释放特性的均匀、水溶性差的含药微粒。通过这种多喷嘴装置设计，我们成功实现了第一阶段的目标，即提高难溶性药物封装的 PPF 生产率的可行性。 SBIR II 期提案的目标是将 4 个多喷嘴装置合并到符合 cGMP、电子控制和监控的 PPF 处理装置中，该装置能够以 1 kg/hr 的中试规模生产速率生产均匀分布的 100 mm 微粒，并且与水溶性差的药物兼容。我们将设计、组装并全面测试该 PPF 系统的机械子系统（目标 1）。与此同时，我们还将设计、组装和测试带有图形用户界面 (GUI) 的完全集成电气系统，该系统将控制机械子系统并调节关键工艺参数，包括临界温度和压力（目标 2）。最后，我们将集成机械和电气组件并优化系统，以实现目标性能指标和颗粒规格（目标 3）。这种系统的开发将证明扩展多喷嘴 PPF 系统以实现全面商业规模生产的可行性，并消除对该技术的外部投资风险，从而使公司能够合作共同开发支持 PPF 的产品。该提案为生产无菌（但非无菌）药物中间体的平台奠定了基础，其释放速率由微粒本身的设计决定，而不是最终剂量形式；因此，它们可以加工成多种口服给药形式，而不改变药物释放特性。这使得药品开发具有很大程度的灵活性——最大限度地降低开发成本并提高患者的依从性。