Can the cavi-precipitation process be exploited to generate smaller size drug nanocrystal?

Abstract

Objective Cavi-precipitation has the potential to generate drug nanocrystals very efficiently. Achieving smaller than 100 nm particle size for organic drug substances still remained a challenge. The objective of this study was to demonstrate if cavi-precipitation technology can be used to generate smaller than 100 nm drug nanocrystal particle. Significance This study demonstrates that cavi-precipitation process can be used to generate drug nanocrystals of the model compound resveratrol (RVT) consists of crystallites of 30–50 nm size. Method RVT was dissolved in different organic solvents to prepare the solvent phase (S-phase). Several stabilizers were tested for the organic phase. A combination of SDS and PVP was used stabilizer system in the aqueous anti-solvent phase (AS-phase). The S-phase was added to the AS-phase inside the Emulsiflex C5 homogenizer. Nanosuspension was characterized by laser diffractometry (LD), photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). The solid state of the suspended particles was investigated by powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC). Results It was found that DMSO, alone or in combination with acetone in the S-Phase generated the smallest size RVT nanocrystals. The optimum solvent (S) antisolvent (AS) ratio (S:AS) was found to be 3.6:56.4 (v:v). Span 20 was identified as the best stabilizer for the organic phase at a ratio (w:w) of 1:3 (Span 20:RVT). The particles precipitated from different solvents were predominantly crystalline. Conclusions The best sample had a mean particle size (LD) of 167 nm [d(0.5)] which was composed of smaller crystallites having 30–50 nm size (SEM).