Re-evaluating the presumed superiority of amorphous nanoparticles over amorphous microscale solid dispersion in solubility enhancement of poorly soluble drugs

摘要

Abstract The solubility enhancement afforded by amorphous drug nanoparticles was demonstrated in several studies to be superior to the traditional amorphization approach by microscale amorphous solid dispersion (or micro ASD in short). A closer look at these studies, however, revealed that they were performed using a very limited number of poorly-soluble drug models (i.e. itraconazole and cefuroxime). Herein we aimed to re-examine the solubility enhancement and physical stability of amorphous nanoparticles relative to that of the micro ASD using a different poorly-soluble drug model, i.e. ciprofloxacin (CIP). Two types of amorphous CIP nanoparticles, i.e. CIP nanorod prepared by pH-shift precipitation and CIP nanoplex prepared by drug-polyelectrolyte complexation, were compared with CIP micro ASD prepared by spray drying with hydroxypropylmethylcellulose (HPMC). The results showed that (1) the solubility enhancement of amorphous drug nanoparticles was not necessarily superior to that of the micro ASD, particularly in their dry-powder form, and (2) the amorphization strategy of drug nanoparticles significantly influenced their solubility enhancement and physical stability. In short, the solubility enhancement was in the order of CIP micro ASD>CIP nanorod>CIP nanoplex, whereas the amorphous state stability during storage was in the order of CIP nanoplex>CIP micro ASD>CIP nanorod. A trade-off thus existed between the solubility enhancement and physical stability of amorphous CIP particles. The present work concluded that the superior solubility enhancement of amorphous drug nanoparticles was not drug independent. Graphical abstract Display Omitted