Systematic investigation of the cavi-precipitation process for the production of ibuprofen nanocrystals.

Cavi-precipitation process is a combinative particle size reduction technology based on solvent-anti-solvent precipitation coupled high pressure homogenization (HPH). The cavi-precipitation can be used for the efficient production of drug nanocrystals (NC) with improved dissolution rate leading to better bioavailability. The work presented here demonstrates the advantage of cavi-precipitation process over the standard HPH processes and standard combination process (decoupled process) where precipitation is performed outside the homogenizer. The model compound ibuprofen (IBP) was solubilized in isopropanol (IPA) to constitute the solvent phase and mixed with the anti-solvent phase (0.1% (w/v) hydroxypropyl methylcellulose with 0.2% (w/v) sodium dodecyl sulphate) at different ratios to carry out the precipitation step. IBP-IPA-Water composition was selected from ternary diagram for a highly supersaturated zone to obtain smaller size particles. The mean particle size [d(0.5)] obtained by this process (300nm) was much smaller when compared to that obtained from the decoupled process (1.5μm). Optimization of the solvent-anti-solvent ratio and drug concentration was necessary to achieve a smaller particle size. PXRD and DSC results revealed that the solid state properties of the original IBP and the prepared NC samples by cavi-precipitation samples were similar.