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

The complex formation of amylobarbitone (AMB) with 2-hydroxypropyl-beta-cyc lodextrin (HP-beta-CD) was investigated in aqueous solution and in the soli d state. The apparent stability constant for complex formation (K-c) calcul ated 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. T he solid dispersion system of AMB/HP-beta-CD in 1:1 molar ratio was prepare d by a freeze-drying method. Differential scanning calorimetry (DSC), x-ray diffractometry, (IR) and H-1 NMR spectroscopy were used to confirm that in clusion 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 e nhanced drug dissolution properties of the prepared complex compared to the physical mixture or the drug alone. The dissolution rate appeared in the f irst 2 min, 25 times greater for the complex than for the drug alone. Furth ermore, in-vivo study revealed that the duration and hypnotic activity of A MB after its oral administration to mice were improved by inclusion.