[Dissolution of nimodipine in an aqueous solution of hydroxyethyl-beta-cyclodextrin and a review of solubility of nimodipine with cyclodextrins]

Abstract

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 beta-cyclodextrin (beta-CD), its derivatives hydroxyethyl-beta-CD (HE-beta-CD), three hydroxypropyl-beta-CD (HP-beta-CD) with various degree of substitution and methyl-beta-CD (M-beta-CD), native alpha-cyclodextrin (alpha-CD), hydroxypropyl-alpha-CD (HP-alpha-CD) and hydroxypropyl-gamma-CD (HP-gamma-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 beta-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-beta-CD, a good solubilizing efficiency was also shown by HE-beta-CD and HP-beta-CDs (with a low degree of substitution), which may be acceptable for the preparation of parenteral nimodipine solutions.