Summary:
The results of a comprehensive study of the dissolution of the calcium antagonist nimodipine in
aqueous solutions of nine cyclodextrins are reported. The used cyclodextrins were native β-cyclodextrin
(β-CD), its derivatives hydroxyethyl-β-CD (HE-β-CD), three hydroxypropyl-β-CD (HP-β-CD)
with various degree of substitution and methyl-β-CD (M-β-CD), native α-cyclodextrin (α-CD),
hydroxypropyl-α-CD (HP-α-CD) and hydroxypropyl-γ-CD (HP-γ-CD). The nimodipine dissolution
was studied as a function of time (up to 14 days) and cyclodextrin concentration up to 0.07 mol/l,
excepting the less soluble β-CD. In this range of cyclodextrin concentration, linear phase diagrams
of nimodipine solubility in the cyclodextrin solutions were observed. From them we derived the
stability constants of the inclusions complexes nimodipine – cyclodextrin (1:1) as well as the
empirical linear equations for the calculation of the saturated nimodipine concentration at a given
cyclodextrin concentration. The most efficient solubiliser of nimodipine was M-β-CD, a good solubilizing
efficiency was also shown by HE-β-CD and HP-β-CDs (with a low degree of substitution),
which may be acceptable for the preparation of parenteral nimodipine solutions.
Key words:
nimodipine – calcium antagonist – cyclodextrins – inclusion complexes –
solubilization – dissolution
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