Possible utility of hydroxyalkylated β-cyclodextrin (β-CyD) derivatives as parenteral drug carriers was investigated, using nimodipine, a dihydropyridine derivative with calcium antagonistic action, as a model drug. The aqueous solubility of nimodipine increased linearly with increase in the concentration of hydroxyalkylated β-CyDs, showing as AL-type phase solubility diagram. The stability constant of nimodipine-hydroxyalkylated β-CyD complexes was in the order of 2, 3-dihydroxypropyl-β-CyD<β-CyD<2-hydroxyethyl-β-CyD<3-hydroxypropyl-β-CyD<2-hydroxypropyl-β-CyD, and the solubilizing ability of the β-CyDs was also taht order. The results of powder X-ray diffractometry and thermal analysis suggested 1 : 3 (guest : host) complex formation of nimodipine with 2-hydroxypropyl-β-CyD in the solid state. The dissolution rate of nimodipine-2-hydroxypropyl-β-CyD complex was much faster than that of the drug alone. Nimodipine-2-hydroxypropyl-β-CyD complex gave higher plasma levels of the drug after intramuscular administration to rabbits, i.e., the area under the plasma concentration-time curve and the maximum plasma concentration of the complex were about 2.5 times higher than those of the drug alone. The muscular damage after the injection of nimodipine was reduced by the administration of the complexed form.
The Pharmaceutical Society of Japan