[Dissolution and signs of supersaturation of nimodipine in aqueous solutions of the cyclodextrins, alpha-CD, HP-alpha-CD, M-beta-CD and HP-gamma-CD].
The dissolution curves of the substance of the calcium antagonist nimodipine in aqueous solutions of four cyclodextrins were determined at ambient temperature in the course of 14 days. The used cyclodextrins were alpha-cyclodextrin (alpha-CD), hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), methyl-beta-cyclodextrin (M-beta-CD, random-methylated), and hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) and their respective concentrations were always 0.05 mol/l. According to the measured dissolution curves, M-beta-CD in aqueous medium was a highly efficient solubiliser, capable to dissolve otherwise sparingly soluble nimodipine into a time-stable aqueous solution, with the saturated concentration of nimodipine 5.15 x 10(-4) mol/l (21.5 mg/100 ml) under the given conditions. M-beta-CD thus appeared to be a more efficient solubiliser than the previously studied HP-beta-CD. The solubilising power of HP-alpha-CD and HP-gamma-CD was much lower and alpha-CD practically did not improve long-term solubility of nimodipine in water. However, in the presence of alpha-CD, HP-alpha-CD, and HP-gamma-CD, respectively, repeated shortterm episodes of formation of supersaturated solutions of nimodipine were observed on the dissolution curves, characterised by peaks of nimodipine concentration. Similar supersaturation episodes were previously observed in the presence of HP-beta-CD. Since the supersaturation caused by cyclodextrins reportedly substantially improved the biological availability of some drugs, the above-mentioned cyclodextrins, and especially natural alpha-CD, could be useful for the enhancement of the low availability of nimodipine from solid oral drug preparations.
Kopecký
F
F
Katedra fyzikálnej chémie lieciv, Farmaceutickej fakulty, Univerzity Komenského, Bratislava.
Kopecká
B
B
Kaclík
P
P
D002121:Calcium Channel Blockers / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D009553:Nimodipine / Q000737:chemistry*; D012995:Solubility; D012996:Solutions
D002121:Calcium Channel Blockers; D003505:Cyclodextrins; D012996:Solutions; D009553:Nimodipine