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: 8089561
• 负责人: Cory Berkland
• 金额: $ 34.57万
• 依托单位: ORBIS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2012-10-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089561
• 关键词: Analgesics; Antibiotics; Beds; Beverages; Biological; Biological Availability; Businesses; Characteristics; Chemicals; Childhood; Development; Disease; Dose; Drug Controls; Drug Delivery Systems; Drug Industry; Effectiveness; Encapsulated; Equipment; Failure; Filtration; Funding; Future; Gastrointestinal tract structure; Gel; Goals; Grant; Guidelines; Health; Human; Industry; Laboratories; Liquid substance; Manufacturer Name; Marketing; Masks; Mechanics; Methods; Microcapsules drug delivery system; Microencapsulations; Monitor; Morphology; Nutrient; Oils; Particle Size; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Positioning Attribute; Practice Guidelines; Process; Production; Property; Recycling; Research; Research Personnel; Solubility; Solutions; Solvents; Stream; Suction; System; Taste Perception; Technology; Testing; Translating; Validation; Vitamin E; Water; base; controlled release; cost; design; drug development; experience; flexibility; improved; in vivo; industry partner; innovation; meetings; novel; novel therapeutics; particle; physical property; product development; prototype; public health relevance; research and development; scale up; wasting

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.

描述（由申请人提供）：该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，这些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其难以配制，这意味着体内生物利用度和有效性较低和/或不稳定。溶解度问题还会降低市场上大部分产品的功效，包括许多止痛药和抗生素。我们新颖的精密颗粒制造 (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，从而改善对药物封装和释放的控制。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），足以满足行业需求。第一阶段研究将展示扩大 PPF 技术以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 技术的多个规模原型，以满足一系列不同的微胶囊规格（目标 1）。我们还将将该技术与 FDA 给出的现行良好生产规范指南（目标 2）相结合，并为该过程设计监控机制和流体回收，以减少材料浪费（目标 3）。成功扩展用于药物输送的 PPF 技术将提高现有药品的生物性能，并能够使用以前在药物开发过程中废弃的 API 生产新的治疗解决方案。 公共卫生相关性：开发药品的有效输送机制与药物本身对于治疗疾病同样重要。然而，制药公司尚未发现一种可靠、可扩展的工艺来持续制造具有受控物理特性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输送载体，测试将一种制造具有明确和可调特性的颗粒的新方法从实验室环境扩展到更广阔的市场的可行性。