Once chemical agents are identified as potential drug candidates, pharmaceutical development relies on the ability to manufacture a stable formulation with predictable and reproducible properties. Crystalline pills have been the primary target product for therapeutic use, but expansion of drug discovery methods has resulted in a massive number of drug candidates, many of which do not possess the desired physical properties for an efficacious product, despite a very strong therapeutic response.
The use of complex pharmaceutical formulations is highly desirable to overcome barriers such as low bioavailability and insufficient solubility or permeability. Such formulations include amorphous phases, nanoparticles, and mixtures with molecular or polymeric excipients. Such products can not typically be studied by the methods used for crystals, and so new analytical methods must be utilized to better understand these materials.
We are developing pair distribution function (PDF) methodology for studying the structure and properties of complex pharmaceutical formulations and molecular materials. Targets include identification and fingerprinting of active pharmaceutical ingredients (APIs), product uniformity, stability, phase quantification, and IP protection. On a deeper level, we are interested in understanding how molecules behave in the amorphous state: why and how different synthesis routes can produce variation in local molecular ordering, and how this ordering impacts the development of crystalline phases.