화학공학소재연구정보센터
Industrial & Engineering Chemistry Research, Vol.54, No.42, 10383-10400, 2015
Idealized Mathematical Model for Pharmaceutical Powder "Micronization" Using Compressed Gas Antisolvent (Re-)Precipitation (GASP): Predicted Performance for the Model Ternary System: Phenanthrene/Toluene/CO2
We consider pharma-motivated processes in which compressed gas (here, COD is employed as an "anti-solvent" (AS), causing drug particle (re)precipitation from an injected presaturated organic solvent microdroplet assumed to be molecularly well-mixed at each instant. It is shown that conditions leading to appreciable homogeneous particle nucleation in this "expanded supersaturated liquid" environment can be sufficiently short-lived that they preclude appreciable particle growth because of encounters with solute molecules or other precipitate particles. This leads to relatively narrow predicted precipitated particle size distributions (PSDs), with a characteristic particle size determined by the typical critical nucleation size. Our mathematical techniques, which exploit the method of characteristics (MOC), make no presumption about PSD-shape and our numerical simulations employ realistic thermophysical properties for the previously studied model system: phenanthrene (surrogate "active pharmaceutical ingredient" [solute], toluene [solvent, S], and compressed CO, [AS]). We explicitly consider initial solvent droplet diameters in the micrometer range and CO, pressures of 52-64 bar and demonstrate the necessity of relaxing frequently made approximations (e.g., nucleation with constant surface energy, negligible Gibbs-Kelvin-Ostwald solubility corrections, solute diluteness,...). Our new methods/parametrizations/performance results for this mathematical model should already help select optimal GASP/SASP operating conditions, and, with suitable extensions, ultimately lead to the development of nearly equally tractable yet sufficiently complete process models.