Summary:
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 a-cyclodextrin (a-CD), hydroxypropyl-a-cyclodextrin (HP-a-CD), methyl-b-cy-
clodextrin (M-b-CD, random-methylated), and hydroxypropyl-g-cyclodextrin (HP-g-CD) and their
respective concentrations were always 0.05 mol/l. According to the measured dissolution curves,
M-b-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 5.15x10 -4 mol/l (21.5 mg/100 ml) under the given conditions. M- b-CD thus appeared
to be a more efficient solubiliser than the previously studied HP-b-CD. The solubilising power of
HP-a-CD and HP-g-CD was much lower and a-CD practically did not improve long-term solubility
of nimodipine in water. However, in the presence of a-CD, HP-a-CD, and HP-g-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 supersatu-
ration episodes were previously observed in the presence of HP-b-CD. Since the supersaturation
caused by cyclodextrins reportedly substantially improved the biological availability of some drugs,
the above-mentioned cyclodextrins, and especially natural a-CD, could be useful for the enhance-
ment of the low availability of nimodipine from solid oral drug preparations.
Key words:
nimodipine – calcium antagonist – cyclodextrins – solubilisation – supersaturated
solutions
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