Abstract
This paper focuses on coprecipitation of pyrazinamide (PZA) with polyvinylpyrrolidone (PVP) using gas antisolvent (GAS) process. Solutions of PZA/polymer in solvent mixtures (acetone and ethanol) with an overall concentration of 20 mg/ml were prepared. The process parameters: pressure, temperature, antisolvent addition rate, solvent composition, and polymer-drug ratio were manipulated to simplify the obtainability of controlled morphology and particle size distribution. Solvent-free particles with reduced crystallinity were precipitated having mean sizes between 311 and 1474 nm. Furthermore, the operating pressure and polymer-drug ratio stood as key parameters affecting the PVP/PZA particle size. The knowledge of the particle characteristics was the main objective in order to identify the crystalline phase and physicochemical properties of the final product. The drug release analyses revealed that by tuning the operating parameters, dissolution rate of PVP/PZA particles could reach near 90%, which was 2.5 times faster than the unprocessed PZA and thus facilitated drug assimilation through the organism.
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