The inhibition effect of high storage temperature on the recrystallization rate during dissolution of nimodipine-Kollidon VA64 solid dispersions (NM-SD) prepared by hot-melt extrusion.

摘要

Nimodipine (NM) solid dispersions (SD) were prepared by hot-melt extrusion with polyvinylpyrrolidone/vinyl acetate copolymer (PVP-VA; Kollidon VA64) as the carrier, then the extrudate was stored at different temperatures (20 degrees C, 40 degrees C, 60 degrees C) after milling. Conventional differential scanning calorimetry and powder X-ray diffraction revealed that the drug was present as an amorphous state in the carrier. The dissolution curves of NM from SD at 37 degrees C in water showed that the rate of recrystallization for NM from SD stored at high temperatures was slower than that from room temperature. The single glass transition temperature (T(g) ) measured by modulated temperature DSC remained constant around 89 degrees C and indicated that the amorphous state of the compound was not altered by heating. However, the C=O vibration of the amide function of Kollidon VA64 increased from 1658 to 1675 cm(-1) was observed in infrared spectra and implied the weakness of H-bonding between the compound and the polymer. The above-mentioned experiments clued to us that suitable postcooking for a short time is good for SD; however, the mechanisms of the changes were still not clear and need further investigation.