In vitro and in vivo evaluation of an amylobarbitone/hydroxypropyl-beta-cyclodextrin complex prepared by a freeze-drying method.

摘要

The complex formation of amylobarbitone (AMB) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated in aqueous solution and in the solid state. The apparent stability constant for complex formation (Kc) calculated by phase solubility and spectral shift methods was 524 M-1 and 568 M-1, respectively. The stoichiometric molar ratio of the complex was estimated to be 1:1 and the solubility of AMB in water was increased about 3 fold. The solid dispersion system of AMB/HP-beta-CD in 1:1 molar ratio was prepared by a freeze-drying method. Differential scanning calorimetry (DSC), x-ray diffractometry, (IR) and 1H NMR spectroscopy were used to confirm that inclusion between the drug and HP-beta-CD occurred. The dissolution behavior of the drug as a physical mixture as well as the prepared complex, showed enhanced drug dissolution properties of the prepared complex compared to the physical mixture or the drug alone. The dissolution rate appeared in the first 2 min, 25 times greater for the complex than for the drug alone. Furthermore, in-vivo study revealed that the duration and hypnotic activity of AMB after its oral administration to mice were improved by inclusion.