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: 7908631
• 负责人: Cory Berkland
• 金额: $ 34.95万
• 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 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908631
• 关键词: 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; Pain; 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个可扩展的过程，用于制造具有均匀尺寸和物理特征的油包装的颗粒，这些颗粒包含油作为输送疏水性药物的载体。水溶性不良的活性药物成分（API）占制药行业发现的所有新化学实体的40％，但是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提出，这转化为低和/或可变的生物利用度和可变的生物利用度和有效性。溶解度问题还降低了市场上大部分产品的功效，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，用于制造具有细调尺寸和物理化学特征的含油颗粒，可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的速度产生干燥的，充满油的微胶囊（尺寸<100 5m），足以满足行业需求。第一阶段的研究将证明将PPF技术扩展为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技术的几种规模的原型，以满足一系列不同的微胶囊规格（AIM 1）。我们还将将该技术与FDA（AIM 2）给出的当前良好制造实践指南相结合，并设计监测机制和流体回收，以减少材料浪费（AIM 3）。成功缩放PPF技术用于药物输送将改善现有药品的生物学性能，并使用先前在药物开发过程中丢弃的API生产新的治疗溶液。 公共卫生相关性：制定药品的有效递送机制与药物本身同样重要。但是，制药公司尚未发现一个可靠的，可扩展的过程，用于始终如一地制造具有受控物理特性和释放曲线的药物颗粒。该项目旨在测试扩展一种新型方法，该方法通过利用封装的油作为可溶性药物的递送工具来制造具有明确和可调性的颗粒的新方法。