Kopecký F, Kopecká B, Kaclík P
Katedra fyzikálnej chémie lieciv Farmaceutickej fakulty Univerzity Komenského, Bratislava.
Ceska Slov Farm. 2003 Jan;52(1):33-8.
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.
报道了对钙拮抗剂尼莫地平在9种环糊精水溶液中溶解情况的综合研究结果。所使用的环糊精有天然β-环糊精（β-CD）、其衍生物羟乙基-β-环糊精（HE-β-CD）、三种不同取代度的羟丙基-β-环糊精（HP-β-CD）以及甲基-β-环糊精（M-β-CD）、天然α-环糊精（α-CD）、羟丙基-α-环糊精（HP-α-CD）和羟丙基-γ-环糊精（HP-γ-CD）。除了溶解性较差的β-CD外，研究了尼莫地平在长达14天的时间内以及环糊精浓度高达0.07 mol/l时的溶解情况。在该环糊精浓度范围内，观察到了尼莫地平在环糊精溶液中溶解度的线性相图。由此我们得出了尼莫地平-环糊精（1:1）包合物的稳定常数以及用于计算给定环糊精浓度下饱和尼莫地平浓度的经验线性方程。尼莫地平最有效的增溶剂是M-β-CD，HE-β-CD和HP-β-CD（低取代度）也显示出良好的增溶效率，这对于制备尼莫地平注射剂可能是可接受的。
