(612b) Precipitation and Stabilization of Sub-Micron Particles of Poorly Water Soluble Drug Fenofibrate by RESOLV

RESOLV, rapid expansion of supercritical solutions into a liquid solvent, has been employed to precipitate and stabilize micron and sub-micron particles of a poorly water soluble drug, Fenofibrate (FNB). In this process, FNB is dissolved in the supercritical fluid (SCF, in this case, Carbon Dioxide). During the rapid expansion of FNB solution in SCF, the solubility of FNB drops and supersaturation is generated, potentially leading to precipitation of ultrafine particles. However, the particle size and its distribution (PSD) is affected greatly by growth and agglomeration of particles, hence the purpose of this study is to employ suitable stabilization approach to curtail the particle size growth.

In order to control particle size, supercritical solutions of FNB prepared at 200 bar and 333 K, were expanded in water (instead of air) with and without stabilizers. Stabilizers such as Sodium Dodecyl Sulphate (SDS), Tween 80, Pluronic F-68, Poloxamer-188, Hydroxypropyl Methyl Cellulose (HPMC), and Sodium Alginate (SA) were used. Co-precipitation of FNB with Poly(lactide-co-glycolide) (PLGA) was also attempted to minimize particle growth and prevent agglomeration. Electrostatic stabilization compared to steric stabilization was found to be more effective in controlling the PSD. It was observed that FNB particles with sizes from 500 nm to 5 µm can be precipitated as a function of type and the amount of stabilizer used. Higher particle concentrations of FNB in aqueous suspensions could be achieved through multiple expansions of supercritical solutions of FNB in to a single collected suspension.