This Small Business Innovation Research (SBIR) Phase I Project will develop a manufacturing process using electrospray for reliably producing nano-suspensions as well as a novel solid oral dosage form for poorly water soluble drugs. Poor water solubility is especially limiting for oral dosage forms, which must be in solution at the site of absorption in the gastrointestinal tract. There is a significant unmet need for new formulation methods for delivering poorly soluble drugs. The electrospray process not only reduces particle size to the nanoscale, but offers some unique manufacturing benefits that include: particle uniformity at the nanoscale; process flexibility with a broad range of chemical and biological agents and solvents and excipients ; single-step engineering of nanocomposite drug/excipient particles or core-shell coated drug particles; particle delivery into liquids or onto solid surfaces. The primary objectives of this proposal are (1) to define key process conditions and electrospray device configurations for generating stable nanoparticle formulations of hard-to-dissolve model drug agents and (2) to develop a novel oral solid dosage form consisting of a rapidly dissolving polymer sheet coated with stablized nanoparticles. Commercially, the knowledge generated by the proposed research will add significantly to our understanding of how this enabling electronanospray manufacturing technology may be used to nanoformulate drugs and how combinations of materials affect nanoparticle stability and ability to be transformed into standard oral dosage forms. Although new high throughput drug screening methods have greatly accelerated the identification of potentially useful drug candidates, compounds identified tend to have a higher molecular weight and chemical features that lead to poorer solubility than traditional drug discovery methods. Therefore, the manufacturing innovation to be developed in this proposal has broad applicability for improving the return on the costly investments required for drug discovery, both because of the simplicity of its use as a potential tool for rapidly determining if solubility improvement could improve performance of insoluble new drug "hits," but also as a means of formulating high value but problematic individual drugs candidates for continued clinical development. In addition, improved solubility leads to improved bioavailability and predicted clinical response; thus, the technical innovation from this project has the potential to fulfill unmet clinical needs for improved drug treatments for difficult-to-treat diseases
