Enchanced dissolution of nifedioine by solid dispersion

Abstract

Solid dispersion of nifedipine in various carriers namely, polyethylene glycols (PEG4000 and PEG6000), poloxamers (poloxamer 188, poloxamer288 and poloxamer 407) and cyclodextrins (β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin) at the drug-carrier ratio of 1:1, 1:3, 1:5 and 1:10 were investigated. The systems were prepared by four different methods which are physically mixed, melting .solvent and kneading methods. The highest improved dissolution rate of nifedipine was found when solid dispersed in poloxamers, followed by secondly PEGs and lastly cyclodextrins. Among poloxamers, the distinctive methods are melting and solvent techniques. In general, the improved dissolution rates were ranked from the most to the least as poloxamer 188, poloxamer288 and poloxamer407 systems respectively (p<0.05). PEG4000 and PEG6000 exhibited a very close value of dissolution rates when compared within the same method and ratio. Similarly to the poloxamers system, melting and solvent method are superior. β-Cyclodextrin and 2-hydroxypropyl-β-cyclodextrin did not form inclusion complex with nifedipine hence showed only a slightly increase of dissolution rate constants. It was found that the drug-carrier ratio of 1:10 showed most conspicuous rates in most cases. The highest dissolution rate was found in nifedipine-poloxamer 188 at the drug-carrier ratio of 1:3 prepared by the melting gave the time at 80% dissolution of only 15 minutes compared with 225 minutes of the pure drug. The possible key mechanisms for improvement of nifedipine dissolution rates in poloxamers could be solubilizing effect, increasing wettability and amorphous transformation which shown via X-ray diffraction and differential scanning calorimetry.