Study of drying processes combined with homogenization to produce amorphous nanoparticles

Abstract

This study aimed to produce nanoparticles with reduced crystallinity by using a combination method. The effect of solid-state transition (different drying processes) coupled with particle size reduction (homogenization) on drug dissolution was systematically investigated. Meloxicam, indomethacin and naproxen with different X-ray diffraction crystal intensity (relative high, medium and low) were selected as models. All drugs were first processed with and without polyvinylpyrrolidone (PVP) to obtain solid dispersions and then high pressure homogenization was used to produce nanosuspensions. Changes of particle morphology might be an important factor to improve the nanosizing efficiency. The smallest particle size (188 nm) could be obtained by using freeze-dried naproxen coupled with PVP after 20 homogenization cycles. Dissolution rates of processed indomethacin and meloxicam without PVP were found similar to their raw drugs. However, significant dissolution improvements were found after homogenization (higher than nanocrystals). Dissolution values of three drug nanoparticle achieved by using PVP dispersions were all higher than 83%. For naproxen, although nanosized solid dispersion possessed the smallest size and amorphous state, its dissolution curve was comparable to the larger sized nanocrystals. It was inferred that the relatively low crystal intensity of the initial compound could be the reason. Nanosuspensions of indomethacin and meloxicam prepared by using the two-step method showed optimized dissolution compared to their nanocrystals and amorphous solid dispersions.