This paper concerns optimization and experimental validation of coprecipitation process parameters for preparing particles of Pyrazinamide and Polyvinylpyrrolidone using gas anti-solvent supercritical method. Mixtures of organic solvents (acetone and ethanol) were selected with various combinations of the drug and the polymer. The central composite design (CCD) was adopted to explore the effect of temperature, pressure, antisolvent addition rate, polymer fraction, and ethanol fraction on particle size distribution (PSD) and solubility. The strong likelihood models were developed for all the responses using Design-Expert software. Polymer fraction was the most important (p<0.0001) factor influencing PSD while pressure and interaction between temperature and polymer fraction significantly affected solubility. The optimal condition was specified at temperature of 50°C, pressure of 120bar, antisolvent rate of 16bar/min, polymer fraction of 30%, and ethanol fraction of 50%. The model was then validated experimentally under the optimal condition and compared with pure PZA and particles obtained from the physical mixture. According to DLS, XRD, FTIR, and FESEM analyses, the crystallinity of PZA-PVP particles was reduced in optimum conditions, leading to higher solubility. Also, the results suggest that it is feasible to produce coprecipitated particles with narrower size distribution by optimized GAS process.

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