Supercritical AntiSolvent micronization of PVA by semi-continuous and batch processing

The biocompatible polymer polyvinyl alcohol (PVA) was successfully micronized by Supercritical AntiSolvent technique in batch (GAS) and semi-continuous (SAS) mode. Using the GAS technique, submicro- and microparticles with mean sizes between 0.4 and 2 mu m, depending on the pressurization rate, were obtained. Using SAS technique nanoparticles, microparticles, balloons and filaments were produced. Nanoparticles presented size distributions as small as about 50-250 nm, microparticles were perfectly spherical, with diameter ranging between 1 and 20 mu m, empty balloons showed diameters up to several tenth of microns and filaments had a length of several hundreds of microns. The reproducibility of the process on different plants was verified: SAS showed immediate reproducibility, GAS for different precipitator volumes requires a control of pressurization times. We also studied the correlation among phase equilibria, jet-break up and morphology of the particles produced by SAS with the aid of the direct visual observation of the process in a windowed precipitator. The observation of the fluid during the precipitation confirmed that nanoparticles were formed in supercritical conditions, microparticles at near critical conditions, and balloons were formed at subcritical single phase conditions. The windowed precipitator also allowed to study the expansion of the liquid phase in the case of the batch process. (c) 2007 Elsevier B.V. All rights reserved.