Expanding Precision Particle Fabrication Technology for the Widespread Control of

描述（由申请人提供）：本项目的总体目标是开发一种可扩展的工艺，用于制造具有均匀尺寸和物理特性的油包封颗粒，该颗粒含有油作为递送疏水性药物的载体。水溶性差的活性药物成分（API）占制药行业发现的所有新化学实体的40%，但研究人员经常在研发阶段丢弃它们，因为它们的不溶性使它们难以配制，这意味着体内生物利用度和有效性低和/或可变。溶解度问题也降低了市场上很大一部分产品的功效，包括许多止痛药和抗生素。我们的新型精密颗粒制造（PPF）技术是一种灵活的单步工艺，用于制造具有微调尺寸和物理化学特性的含油颗粒，从而改善对药物包封和释放的控制。我们假设，该技术的缩放版本将以至少10 kg/min的速率生产干燥的充油微胶囊（尺寸<100 5 m），足以满足工业需求。第一阶段的研究将证明扩大PPF技术的可行性，供制药公司广泛使用。我们的研究团队将开发现有PPF技术的几个缩放原型，以满足一系列不同的微胶囊规格（目标1）。我们还将把该技术与FDA（目标2）给出的现行良好生产规范指南相结合，并为该过程设计一个监测机制和流体回收，以减少材料浪费（目标3）。PPF药物输送技术的成功规模化将提高现有药品的生物学性能，并能够使用以前在药物开发过程中丢弃的API生产新的治疗解决方案。 公共卫生相关性：开发药物产品的有效输送机制与药物本身治疗疾病同样重要。然而，制药公司尚未发现一种可靠的、可扩展的工艺，用于一致地制造具有受控物理性质和释放曲线的药物颗粒。该项目旨在通过利用封装油作为难溶性药物的递送载体，测试将用于制造具有明确定义和可调性质的颗粒的新方法从实验室环境扩展到更广泛市场的可行性。

DESCRIPTION (provided by applicant): This overall goal of this project is to develop a scalable process for fabricating oil encapsulated particles with uniform sizes and physical characteristics that contain oil as a vehicle for delivering hydrophobic drugs. Poorly water soluble active pharmaceutical ingredients (APIs) represent 40% of all new chemical entities discovered by the pharmaceutical industry, but investigators often discard them in the R&D phase because their insolubility renders them difficult to formulate, which translates to low and/or variable bioavailability and effectiveness in vivo. Solubility problems also decrease the efficacy of a significant portion of products on the market, including many pain relievers and antibiotics. Our novel Precision Particle Fabrication (PPF) technology is a flexible, single-step process for fabricating oil-containing particles with finely tuned sizes and physicochemical characteristics that enable improved control over drug encapsulation and release. We hypothesize that a scaled version of this technology will produce dried, oil-filled microcapsules (size <100 5m) at a rate of at least 10 kg/min, more than adequate for industry needs. Phase I research will demonstrate the feasibility of scaling PPF technology for broad use by pharmaceutical companies. Our research team will develop several scaled prototypes of the existing PPF technology to meet a range of varying microcapsule specifications (Aim 1). We will also integrate the technology with current Good Manufacturing Practice guidelines given by the FDA (Aim 2) and design a monitoring mechanism and fluid recycling for the process to decrease material waste (Aim 3). Successful scaling of the PPF technology for drug delivery will improve the biological performance of existing pharmaceutical products and enable production of new therapeutic solutions using APIs previously discarded in the drug development process. PUBLIC HEALTH RELEVANCE: Development of effective delivery mechanisms for pharmaceutical products is just as important as the drugs themselves for treatment of disease. However, pharmaceutical companies have yet to discover a reliable, scalable process for consistently fabricating drug particles with controlled physical properties and release profiles. This project aims to test the feasibility of expanding a novel method for fabricating particles with well-defined and tunable properties from the laboratory setting to the broader marketplace by leveraging encapsulated oil as a delivery vehicle for poorly- soluble drugs.