Production of pure indinavir free base nanoparticles by a supercritical anti-solvent (SAS) method.

Julieta C Imperiale, Gabriela Bevilacqua, Paulo de Tarso Vieira E Rosa, Alejandro Sosnik

Index: Drug Dev. Ind. Pharm. 40(12) , 1607-15, (2014)

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Abstract

This work investigated the production of pure indinavir free base nanoparticles by a supercritical anti-solvent method to improve the drug dissolution in intestine-like medium.To increase the dissolution of the drug by means of a supercritical fluid processing method.Acetone was used as solvent and supercritical CO2 as antisolvent. Products were characterized by dynamic light scattering (size, size distribution), scanning electron microscopy (morphology), differential scanning calorimetry (thermal behaviour) and X-rays diffraction (crystallinity).Processed indinavir resulted in particles of significantly smaller size than the original drug. Particles showed at least one dimension at the nanometer scale with needle or rod-like morphology. Results of X-rays powder diffraction suggested the formation of a mixture of polymorphs. Differential scanning calorimetry analysis showed a main melting endotherm at 152 °C. Less prominent transitions due to the presence of small amounts of bound water (in the raw drug) or an unstable polymorph (in processed IDV) were also visible. Finally, drug particle size reduction significantly increased the dissolution rate with respect to the raw drug. Conversely, the slight increase of the intrinsic solubility of the nanoparticles was not significant.A supercritical anti-solvent method enabled the nanonization of indinavir free base in one single step with high yield. The processing led to faster dissolution that would improve the oral bioavailability of the drug.