Inhibition of crystallization and growth of celecoxib nanoparticles formed from volatile microemulsions

The inhibitory effect of ammonium glycyrrhizinate (AG) on crystallization of celecoxib (CXB) nanoparticles in aqueous medium was studied. CXB nanoparticles in powder form were prepared by rapid evaporation of all solvents from a volatile oil-in-water microemulsion. A powder containing 13 wt % CXB was obtained by immediate conversion of microemulsion droplets into nanoparticles by spray drying. CXB was amorphous in this powder, which could be easily dispersed 1 wt % in water as nanoparticles. However, these particles crystallized rapidly upon dispersion, and a significant particle growth was observed. The natural surfactant, AG, which is US Food and Drug Administration approved for oral administration, inhibited crystallization of CXB, enabling a stable dispersion of nanoparticles with average size of 14 nm. Molecular dynamics simulations revealed rapid attachment of glycyrrhizinate to the growing CXB crystal and suggested that crystallization inhibition is due to interactions between the hydrophobic part of glycyrrhizinate and the phenyl moieties of CXB.