PFI-TT: Research and Development of a Novel Printer for Small Molecular-Based Medicines That Enhances Their Dissolution Properties and Cost-Effectiveness.

这个PFI项目的更广泛的影响/商业潜力将是提高药物研究、开发和制造的速度和成本效益，最终降低新型尖端药物的成本，并使人们更容易服用抗击某些疾病所需的药物组合。目前在药物发现和制造方面的许多做法都已有百年历史，导致质量差，患者依从性差，可扩展性差，许多药物稀缺。建议的方法与制药部门的现有做法完全不同，增强了药物中活性成分的性质，降低了临床前测试所需的溶剂量，从而减少了有毒化学废物，但与许多现有药物和剂型(如药丸、胶帽、贴片、注射剂等)兼容。如果成功，这项拟议的技术可能会将药物开发时间缩短几年，使将多种药物组合成为每个患者量身定做的单一药片或贴片变得更容易，并减少由于身体消除或未使用的处方药而浪费的宝贵有效成分的数量。拟议的项目具有重大的智力价值，因为它利用半导体行业和纳米技术的技术来解决制药科学、开发和制造中的长期问题。该项目的核心工艺可以精确和准确地打印活性药物成分(原料药)，同时还可以在不使用强或有毒溶剂的情况下增强其溶解能力。它将促进对药物化合物的热性质、分子结构和晶体结构之间的联系以及它对溶出性和生物利用度的影响的理解，这一点它得到了加强。虽然一些化合物已经显示了这些能力，但更广泛的制药研究界仍然无法获得这些能力。这一跨学科的项目将使分子化学家、生物学家和药理学家能够广泛使用这一能力，使他们能够将更多的时间用于优化小分子疗法的效力和特定部位的结合，而不会面临溶解瓶颈。拟议的工作承诺释放数百万已经合成的化合物的治疗潜力，这些化合物由于溶解性差而在材料库中萎靡不振，并创造出前所未有的复杂的组合疗法，将利用深度学习和数据驱动的医学科学。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this PFI project will be to enhance the rate and cost-effectiveness of pharmaceutical research, development and manufacturing, ultimately lowering the cost of new, sophisticated medicines, as well as making it easier for people to take combinations of medicines required to combat some diseases. Many current practices in drug discovery and manufacturing are century-old, resulting in poor quality, poor patient compliance, poor scalability, and scarcity of many medicines. The proposed approach differs radically from existing practices in the pharmaceutical sector, enhances the properties of active ingre-dients in medicines, drives down the amount of solvents required for pre-clinical testing and thus reducing toxic chemical waste, yet is compatible with many existing drugs and dosage forms (e.g. pills, gel caps, patches, injections, etc.). If successful, the proposed technology could short-en by several years the drug development timeline, make it easier to combine multiple med-icines into a single pill or patch tailored to each patient, and reduce the amount of precious active ingredient being wasted due to body elimination or unused prescription medicines. The proposed project has significant intellectual merit, in that it leverages techniques from the semiconductor industry and nanotechnology to address long-standing problems in pharmaceutical science, development, and manufacturing. The process at the core of this project can print active pharmaceutical ingredients (APIs) with precision and accuracy, while also enhancing their dissolution without resorting to strong or toxic solvents. It will advance understanding of thermal properties of pharmaceutical compounds, the link between molecular structure and crystal structure, and its influence on dissolution properties and bioa-vailability, which it enhances. While these capabilities have been shown for some compounds, they remain unavailable to the broader pharma research community. This multi-disciplinary project will make the capability widely available to molecular chemists, biologists, and pharmacologists, allowing them to devote more of their time to optimizing small molecular therapeutics for potency and site-specific binding, without facing solubility bottlenecks. The proposed work promises to unlock the therapeutic potential of millions of al-ready synthesized compounds that are languishing in material libraries due to their poor solubility, and to create combination therapies of unprecedented sophistication that will leverage deep learning- and data-driven medical science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.