AIR Option 1: Technology Translation - Proof-of-concept testing and technology translation for engineered nanocomposites

这个PFI：空气技术转换项目专注于将创新的表面修饰科学与沸腾床涂层技术相结合，用于生产精细的药物纳米复合颗粒，以填补目前缺乏可扩展和经济可行的方法来生产高度生物利用性、没有砂砾口感的药物复合颗粒的技术空白，这对吞咽障碍患者来说是不可取的。转化为科学的技术具有以下独特特点：即使对难溶的药物也具有非常快的溶出速度，尺寸小到足以并入口腔崩解剂量，以及出色的流动性和搬运性能，使用传统稳健的加工方法提供了典范的性能，与领先的竞争技术如喷雾干燥和热熔融挤压以提高生物利用度，或冷冻干燥快速崩解剂型在该市场领域相比，这些方法导致了高效、可扩展和具有成本效益的生产。该项目通过结合表面科学的基本方面来实现这一目标，以降低载体颗粒的凝聚力并稳定纳米药物颗粒，这些纳米药物颗粒的直径小于人类头发直径的300倍，以保持其较大的表面积，从而产生一种概念验证的高度生物利用的药物复合颗粒，该颗粒带有味道，小于50微米，即小于人类头发的直径。这一合作关系与合同制造商Catalent Pharma Solutions及其制药公司客户合作，在口腔崩解剂型的技术和监管方面以及与将基于科学的技术转化为可能导致竞争性商业现实的道路相关的其他方面提供指导，如可专利性、市场研究、融资和商业化。商业化的最终成果是一个强大的制造平台，适用于任何难于溶于水的药物，并形成快速溶解的药物复合小颗粒，可用于咀嚼片、糖浆、薄膜或含片，针对有吞咽障碍的患者，从而提高患者的依从性。作为参考，大多数新发现的药物几乎不溶于水；而仅吞咽困难一项的市场目前就超过30亿美元/年。预计在未来五到十五年内，潜在的经济影响将远远超过每年1亿美元，这将有助于提高美国在制药行业的竞争力，因为纳米结构颗粒是通过具有可扩展性、可重复性、低成本和高产量的方法生产的，而且产品将具有更好的生物利用度，更小，是下一代制药制造的重要组成部分。同样，它也会对其他行业产生影响，例如食品、农用化学品、养分输送、化妆品以及牙科和生物材料。从长远来看，社会影响将体现在强大的制造平台上，该平台将导致产品提供更好的患者舒适性，从而提高合规性，并使用简单、具有成本效益的工艺来改善性能，并通过减少与工厂工人的相关暴露而降低使用纳米颗粒的风险。

This PFI: AIR Technology Translation project focuses on translating innovative surface modification science with fluid-bed coating technology for producing fine drug nano-composite particles to fill current technology gap of lack of scalable and economically feasible methods to produce highly bioavailable drug composite particles that do not have a gritty mouth-feel, which is undesirable for patients with swallowing disorders. The translated science-based technology has the following unique features: very fast dissolution even for poorly water soluble drugs, a size small enough for incorporation into orally disintegrating dosages, and excellent flow and handing properties that provide exemplary performance using conventional robust processing methods that lead to efficient, scalable and cost-effective manufacturing when compared to the leading competing technologies such as spray drying and hot-melt extrusion for bioavailability enhancement, or freeze-dried fast disintegrating dosage forms in this market space. The project accomplishes this goal by combining fundamental aspects of surface science to reduce cohesion of carrier particles and to stabilize nano-drug particles, which are 300 times smaller than the diameter of human hair, to preserve their large surface area resulting in a proof-of-concept highly bioavailable drug composite particle that is taste-masked, and is less than 50 microns, i.e., smaller than the diameter of human hair. The partnership engages Catalent Pharma Solutions, a contract manufacturer, along with their pharmaceutical company clients to provide guidance in the technological as well as regulatory aspects of orally disintegrating dosage forms and other aspects such as patentability, market research, financing, and commercialization as they pertain to the potential to translate the science based technology along a path that may result in a competitive commercial reality. The final output of the commercialization is a robust manufacturing platform that is applicable to any poorly water soluble drug and forming fast dissolving drug-composite small particles that can be used in chewable tablets, syrups, strip-films or lozenges, targeting patients having swallowing disorders, thus increasing patient compliance. As a reference, the majority of newly discovered drugs are almost insoluble in water; while the market for dysphagia alone is currently over $3B/year. The potential economic impact is expected to be well over $100M/year in the next five to fifteen years, which will contribute to the U.S. competitiveness in the pharmaceutical sector, since nanostructured particulates are produced via methods that have scalability, reproducibility, low cost, and high-yield, and the products will have better bioavailability, are smaller and are essential components of next generation pharmaceutical manufacturing. Similarly, it can have an impact on other industries; such as; food, agrochemical, nutrient delivery, cosmetics, as well as dental and bio-materials. The societal impact, long term, will be in robust manufacturing platform that leads to products that provide improved patient comfort, hence compliance, and improved performance using simple, cost-effective processes, as well as have the reduced-risk of using nano-particles through lack of associated exposure to factory workers.