Multiplexed Nucleation Approaches for Enhanced High Throughput Screening of Co-Crystals

DESCRIPTION provided by applicant Poor water solubility of active pharmaceutical ingredients APIs increasingly poses challenges to drug development with andgt of new APIs suffering from this issue Co crystallization is a novel strategy for overcoming these challenges particularly for those APIs that are not readily derivatized with hydrophilic groups Improvements to high throughput screening HTS for co crystallization will expand the number of readily soluble new chemical entities for API formulation and will give Public Health benefit deriving from new safer and more bioavailable pharmaceuticals The goal of this Phase I grant is to develop improved methods for API co crystal screening that incorporate complementary crystallization approaches multiplexed mechanochemical solid state compression with shear and HTS compatible solution crystallization technologies that use surface chemistry modifications to give nucleation enhancements that improve crystallization outcomes By incorporating these orthogonal crystal nucleation approaches into a unified workflow the probability and speed of co crystal formation in HTS screening efforts can be improved DeNovX will demonstrate the utility of both multiplexed direct compression solid synthesis and mini drop solution crystallization using innovative surface assisted nucleation in well HTS plates Objectives for Phase II include quantitation of the integrated workflow efficiencies using and well HTS and an emphasis on more diverse synthons with the goal of using HTS handling and analytical methods to generate new co crystal compositions that are relevant to unmet needs in pediatric and select orphan indications PUBLIC HEALTH RELEVANCE The impact to Public Health will derive from an acceleration in the discovery and characterization of new pharmaceutical co crystal compositions using high throughput screening in expanding this knowledge base to support regulatory decision making and in the application of these co crystallization technologies to overcoming the water solubilit issues that plague andgt of drugs in development Advances in co crystal discovery and use ultimately will result in pharmaceuticals for the patient that have better bioavailability efficac and safety Co crystallization may be particularly beneficial for APIs that are intractable to standard solubility derivations or in orphan and pediatric indications where the lack of blockbuster revenue potential has limited the investment in solubility enhancements