Expanding Precision Particle Fabrication Technology for the Widespread Control of

描述(由申请人提供)：这个项目的总体目标是开发一种可扩展的工艺，用于制造具有统一尺寸和物理特性的油包覆颗粒，其中包含油作为输送疏水药物的载体。难于溶于水的活性药物成分(API)占制药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，这意味着它们在体内的生物利用度和有效性低和/或可变。溶解性问题也会降低市场上相当一部分产品的疗效，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，用于制造尺寸和物理化学特性可调的含油颗粒，从而改进对药物封装和释放的控制。我们假设，这项技术的规模化版本将以至少10公斤/分钟的速度生产干燥的、充满油的微胶囊(尺寸为100 5米)，足以满足行业需求。第一阶段研究将论证扩大PPF技术供制药公司广泛使用的可行性。我们的研究团队将开发现有PPF技术的几个规模化原型，以满足一系列不同的微胶囊规格(目标1)。我们还将把这项技术与FDA提供的当前良好制造规范指南(目标2)相结合，并为该过程设计一个监测机制和液体回收，以减少材料浪费(目标3)。用于药物输送的PPF技术的成功扩展将改善现有药物产品的生物学性能，并能够使用以前在药物开发过程中丢弃的原料药生产新的治疗解决方案。 与公共卫生相关：发展有效的药品输送机制与治疗疾病的药物本身同样重要。然而，制药公司还没有发现一种可靠的、可扩展的工艺，可以始终如一地制造具有受控物理性质和释放曲线的药物颗粒。该项目旨在测试将一种新的方法从实验室环境扩展到更广泛的市场的可行性，该方法可用于制造具有明确定义和可调性质的颗粒，方法是利用胶囊油作为难溶药物的输送载体。

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.