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

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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.