UROP Research Mentor Project Submission Portal: Submission #895

Overall Research Project Description Synopsis
An undergraduate project is available for students in chemistry or physics that are interested in the use of ultra-high magnetic field nuclear magnetic resonance (NMR) spectroscopy to characterize solid forms of active pharmaceutical ingredients (APIs). Required background: undergraduate chemistry or physics students, completed 2 years of study minimum. Locations: NMR spectroscopy at MagLab; Synthesis, X-ray, Computation at FSU

Experience and benefits to the student
Undergraduate researchers will learn techniques in solid-state mechanochemical synthesis (ball milling and related solid-state methods), multinuclear solid-state NMR (SSNMR) spectroscopy (1H, 2H, 13C, 14N, 15N, 17O, 23Na, 35Cl, and others), powder X-ray diffraction (pXRD), and basic quantum computational methods like density functional theory (DFT) as applied to NMR crystallography. This introductory research project will provide strong grounding in solid-state chemistry and/or physics, with a flexible set of project options available.

Project details
Most drug products, or active pharmaceutical ingredients (APIs), are synthesized, manufactured as dosage forms, stored, and ingested as solid materials. Of these, the majority are formulated as hydrochloride (HCl) salts, for purposes of increasing solubility, stability, and bioavailability. Numerous structural forms of the same drug, known as polymorphs, can have markedly different properties, and also represent unique intellectual property. Furthermore, new solid forms, produced as multi-component crystals, are currently of great interest in the pharmaceutical and crystal engineering communities, due to the possibility of tuning the materials to have desirable pharmaceutical properties. Paramount to the successful crystal engineering is our ability to characterize molecular level structure, and also to predict molecular structure using spectroscopic, diffraction, and computational methods. Undergraduate researchers will work under the supervision of the PI and senior graduate students/post-docs on this project.

In the proposed undergraduate research project, mechanochemical ball milling will be used to synthesize an array of multi-component cocrystals that involve HCl salts of several APIs and pharmaceutically acceptable coformers. Careful consideration in the crystal engineering of these systems will be undertaken. Starting reagents and final products will be characterized with SSNMR and pXRD. This experimental data will be used in a plane-wave DFT framework to solve the crystal structures of these systems. Aspects of this work will involve collaborations with other scientists from around the world, and several major pharmaceutical companies.