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Dissolution of Nimodipine in Aqueous Solutions of Hydroxyethyl-β-cyclodextrin and theSurvey of Nimodipine Solubilization with Cyclodextrins


Authors: F. Kopecký;  B. Kopecká 1;  P. Kaclík
Authors‘ workplace: Katedra fyzikálnej chémie liečiv Farmaceutickej fakulty Univerzity Komenského, Bratislava 1Katedra farmaceutickej analýzy a nukleárnej farmácie Farmaceutickej fakulty Univerzity Komenského, Bratislava
Published in: Čes. slov. Farm., 2003; , 33-38
Category:

Overview

The results of a comprehensive study of the dissolution of the calcium antagonist nimodipine inaqueous 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 dissolutionwas 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 diagramsof nimodipine solubility in the cyclodextrin solutions were observed. From them we derived thestability constants of the inclusions complexes nimodipine – cyclodextrin (1:1) as well as theempirical linear equations for the calculation of the saturated nimodipine concentration at a givencyclodextrin concentration. The most efficient solubiliser of nimodipine was M-β-CD, a good solubilizingefficiency 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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