Expanding Precision Particle Fabrication Technology for the Widespread Control of

描述（由申请人提供）：目前在医药市场中存在对能够准确和有效地控制水溶性差的化合物的释放的微粒的迫切需要。尽管这些水溶性差的药物预计具有很高的临床疗效，但由于成本高，它们往往在研究的早期阶段被拒绝 以及水溶性差的分子配制和递送的技术困难。 Orbis Biosciences的新型精密颗粒制造（PPF）技术有可能解决这种药物制剂的困境，它允许灵活、具有成本效益的单步封装水溶性差的药物，同时还提供对颗粒大小、形状、组成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系统生产具有精确设计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，能够生产具有确定尺寸和释放特性的均匀的、水溶性差的含药物微粒。通过这种多喷嘴单元设计，我们成功地实现了我们的第一阶段目标，即确定提高用于封装难溶性药物的PPF生产率的可行性。该SBIR第II阶段提案的目的是将这些多喷嘴单元中的4个并入cGMP就绪、电子控制和监测的PPF处理装置中，该装置将能够以1 kg/hr的中试规模生产速率生产均匀分布的100 mm微粒，并且将与水溶性差的药物相容。我们将设计、组装和全面测试PPF系统的机械子系统（目标1）。同时，我们还将设计、组装和测试一个完全集成的电气系统，该系统具有图形用户界面（GUI），可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大多喷嘴PPF系统的完全商业规模生产的可行性，并降低外部对该技术的投资风险，从而使公司能够合作开发PPF产品。该提议为生产无菌（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，而不是最终的剂型;因此，它们可以被加工成各种口服递送形式而不改变药物释放特性。这使得在药品开发中具有很大程度的格式灵活性-最大限度地降低开发成本并提高患者依从性。

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.