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


OBJECTIVE
To increase the dissolution of the drug by means of a supercritical fluid processing method.


METHODS
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).


CONCLUSIONS
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.


CONCLUSIONS
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.
The Group of Biomaterials and Nanotechnology for Improved Medicines (BIONIMED), Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires , Buenos Aires , Argentina .
Julieta C
JC
Imperiale
Gabriela
G
Bevilacqua
Paulo de Tarso Vieira E
Pde T
Rosa
Alejandro
A
Sosnik
D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D019469:Indinavir / Q000138:chemical synthesis*; D053758:Nanoparticles / Q000737:chemistry*; D012997:Solvents; D014961:X-Ray Diffraction
D012997:Solvents; D019469:Indinavir
Drug dissolution; HIV; drug solubility; indinavir free base; pure drug nanoparticles; supercritical anti-solvent method