Abstract:
Nifedupine solid dispersions in polyethylene glycols (PEG4000 and PEG6000), poloxamers (poloxamer188 poloxamer288 and poloxamer407), [beta]-cyclodextrin (BCD) and 2-hydroxypropyl-[beta]-cyclodextrin (HPBCD), at the drug:carrier ratio if 1:1, 1:3, 1:5, and 1:10 were investigated. The systems were prepared by melting, solvent and kneading method and compared to physical mixtures. It was found that the drug:carrier ratio of 1:10 and by melting and solvent methods showed most conspicuous dissolution rates in most systems (p<0.05). The most markedly improved rate was exhibited from the poloxamers. The prominently increased dissolution rates and the time for 80% drug dissolved of only 15 min were obtained in poloxamer 188 and poloxamer 407 from melting method at the 1:3, 1:5, 1:10 ratios. PEG 4000 and PEG 6000 exhibited a very close dissolution rates when compared within the same method and ratio. Whereas BCD and HPBCD showed only a slightly increase of dissolution rate constants. Physicochemical characterizations showed that the possible key mechanism for fast release was the amorphous transformation of nifedipine in carriers, which shown via X-ray diffraction and differential scanning calorimetry. The marked improved wettability and solubility of nifedipine also gave beneficial effects. The intermolecular H-bonding between nifedipine and carriers was exhibited from the infrared spectral analyses.
