1. PROJECT SUMMARY: During the last few months, we have discovered that all recent experimental and modeling work on the production of valuable pharmaceutical powders (insulin, antibiotics, anti-virals, cortisones,..) was not exploiting or even taking into account a rather basic phenomenon that could lead to very significant future product/process improvements. Our preliminary calculations revealed that if sufficiently small solvent droplets could be sprayed into supercritical CO2 "anti-solvent?" the ensuing dilation rate would actually be large enough to dramatically reduce the coagulation rate constant and narrow the PSD of precipitating particles in this unusual particle processing environment! EAGER Program Objectives: The purpose of this 1-year Early Concept/Exploratory Research(EAGER) Grant application to NSF-CBET is to enable our immediate exploration/evaluation of this exciting new research direction. Not one of the many other groups worldwide (often affiliated with Chemistry departments) has even considered this interesting type of coupling [between homogeneous kinetics and fluid deformation rate], not to mention the possible practical implications for pharma particle production using more advanced injectors---ie, producing smaller solvent droplet diameters (ca. sub 10-micron) to exploit these predicted benefits. Intellectual Merit: Our brief initial quantitative account of this potentially transformative discovery, along with our preliminary calculations already demonstrating its remarkable PSD-consequences. This present EAGER Program will allow us to immediately develop this initial discovery into a more general process modeling approach, even enabling inclusion of the effects of other potentially important types of solvent non-uniformities (eg., spatial gradients) on coagulation rate constants, including the effects of net particle charge and fluid temperature non-uniformity. Uniqueness of Approach: Because of our unusual interdisciplinary backgrounds (embracing ChE, Fluid Physics, Mech E, and AeroE) we are in a unique position to investigate this exciting new class of possibilities, and then move on (via a 3-year follow-on NSF/CBET Grant) to improve the modeling of several other key aspects of the attractive supercritical fluid particle processing environment. Broader Impacts: The intellectual and economic impact of this work via its effect on future modeling efforts in the many SCF-based industries (pharma-, catalyst synthesis, energetic materials, food technologies,) already exploiting supercritical fluids is likely to be very significant especially as a result of our university lectures, talks at international conferences (2010 IAC, and AIChE) and universities, provisional patent disclosure, and, of course, our archival publications,
Late in the course of an earlier NSF program at Yale Prof. Daniel E. Rosner discovered that all recent experimental and modeling work on the production of valuable pharmaceutical powders (insulin, antibiotics, anti-virals, cortisones,……) was not exploiting (or even accounting for) rather basic phenomena that could lead to very significant future product/process improvements. His preliminary estimates revealed that if sufficiently small solvent droplets could be sprayed into supercritical CO2 "anti-solvent", the ensuing dilation rate would actually be large enough to dramatically reduce the coagulation rate constant, reduce the mean particle size, and narrow the PSD of precipitating particles in this unusual particle processing environment! He also identified other opportunities for process modifications, including the exploitation of "temperature contrast". This prospect has motivated our present studies* of how steep temperature gradients can modify coagulation rate dynamics. The present short-term EAGER Grant enabled us to extend our preliminary investigations in exciting new research directions------commencing the summer of 2010. It has lead to 4 archival publications and one provisional patent application. Not one of the many other groups worldwide (often affiliated with Chemistry departments) has even considered the promising issues we are studying------especially the interesting couplings between homogeneous kinetics and the non-equilibrium state of the carrier fluid. This fundamental work is expected to have practical implications for future pharmaceutical particle production by enabling more effective choices of processing conditions.
