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: 8921824
• 负责人: Nathan H Dormer
• 金额: $ 51.32万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921824
• 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; 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(申请人提供)：目前药品市场对能够准确和有效地控制难于溶于水的化合物的释放的微粒有迫切的需求。尽管这些难溶于水的药物被认为具有很高的临床疗效，但由于成本较高，它们在研究的早期阶段经常被拒绝。 以及配制和传递水溶性较差的分子的技术困难。奥比斯生物科学公司的新型精密颗粒制造(PPF)技术具有解决这一药物配方困境的潜力，它允许对难溶于水的药物进行灵活、经济高效的一步封装，同时还可以对颗粒大小、形状、组成和释放情况进行精确控制。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工程物理特性的载药颗粒。在SBIR第一阶段实验室到市场的资助下，我们设计和优化了一个由12个单独的喷嘴组成的多喷嘴单元，能够产生确定尺寸和释放特性的均匀的、难于溶于水的含药微粒。通过这种多喷嘴单元的设计，我们成功地实现了第一阶段的目标，即建立了提高难溶药物胶囊的PPF产率的可行性。SBIR第二阶段提案的目标是将这些多喷嘴装置中的4个纳入可用于cGMP的电子控制和监测的PPF处理装置，该装置将能够以1公斤/小时的中试生产速度生产均匀分布的100毫米微粒，并将与难溶于水的药物兼容。我们将设计、组装和全面测试该PPF系统的机械子系统(目标1)。同时，我们还将设计、组装和测试具有图形用户界面(GUI)的完全集成的电气系统，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，我们将整合机械和电气部件，并对系统进行优化，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大多喷嘴PPF系统用于全面商业规模生产的可行性，并降低对该技术的外部投资，从而使各公司能够合作共同开发具有PPF功能的产品。这一建议为平台生产无菌(但非无菌)药物中间体奠定了基础，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，它们可以加工成各种口服给药形式，而不会改变药物释放特性。这使得药物产品的开发具有很大程度的格式灵活性--将开发成本降至最低，并提高了患者的依从性。