Nanosizing Coamorphous Drugs Using Top-Down Approach: The Effect of Particle Size Reduction on Dissolution Improvement

Nanotechnology and coamorphous are both advanced technologies that can effectively improve the solubility of drugs. This study has been the first attempt to combine these two approaches to construct the coamorphous nanoparticles to improve the dissolution and investigated the effect of physical properties of coamorphous solid on the nanosizing process. Two types of coamorphous solid, i.e., curcumin-artemisinin and quercetin-lysine, were selected as models. Coamorphous curcumin-artemisinin could highly contribute to the size reduction during milling compared to the crystalline form, which might attribute to the change of crystallinity. Nanosized coamorphous curcumin-artemisinin showed higher dissolution than nanocrystals and single coamorphous sample. However, quercetin-lysine coamorphous nanoparticles did not reflect significant dissolution improvement compared with the microsized sample. The difference of initial dissolutions for both could be the main reason. The directly mixing and drying method was confirmed to be an effective and simple approach to maintain the dissolution of nanosized coamorphous sample.