Effect of HPMCAS on recrystallization inhibition of nimodipine solid dispersions prepared by hot-melt extrusion and dissolution enhancement of nimodipine tablets.

Abstract

In current study, a novel nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) with Hypromellose methylcellulose acetate succinate (H type and fine grades, HPMCAS-HF) for its excellent recrystallization inhibition effects. NM was confirmed to exist as an amorphous state in NM-SD by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and scanning electron micrographs (SEM). FT-IR analysis illustrated hydrogen bond interaction between drugs and excipients in NM-SD. The release behavior of NM-SD tablets was investigated in the dissolution medium of pH 6.8 for the in vitro study, which showed that the release of nimodipine could be realized in vitro without recrystallization within two hours. The in vivo pharmacokinetic profiles study in Sprague-Dawley rats was also determined. It was obvious that the Cmax value of NM-SD tablets made by dry granulation was slightly higher than Nimotop®, while the area under the curve, AUC(0-t) exhibited no significant difference between them. In conclusion, the solubility of NM and dissolution rate of NM-SD tablets were greatly improved by HME due to the recrystallization inhibition characteristic of HPMCAS-HF.