Fabrication, characterization, stability and in vitro evaluation of nitrendipine nanocrystals by media milling

摘要

Nanocrystal is one of the classic formulation strategies for poorly water-soluble drugs. In this study, nitrendipine (NTD) nanocrystals were prepared using a media milling method for the first time. Comprehensive physical characterizations of NTD nanocrystals were carried out including hydrodynamic diameter, polydispersity index, zeta potential, transmission electron microscope, scanning electron microscope, differential scanning calorimetry, powder X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and optical microscope. The optimized nanocrystals stabilized by 1.25% (w/v) HPMC-E5 and 0.4% (w/v) SDS were oblong-shaped with a particle size of 256.5 +/- 6.6 nm. The crystal structure of NTD nanocrystals was maintained during the milling process. but a portion of crystal was transformed to amorphous state. No obvious interaction was detected between the drug and stabilizers. In addition, the physical stability and in vitro dissolution were assessed. NTD nanocrystals were physically stable during the storage at 25 +/- 2 degrees C for 30 days. In the dissolution test, for NTD nanocrystals, the accumulative release after 20 min was over 80% in the media of 0.3% SDS, which was 4-fold higher than those of physical mixture and commercial tablets. The results indicated that NTD nanocrystals exhibited superior dissolution due to the reduced particle size. In conclusion, drug nanocrystal produced by wet media milling is a promising strategy for improving the solubility and dissolution rate for NTD. (C) 2018 Elsevier B.V. All rights reserved.