Tanaka M, Takahashi M, Kuwahara E, Koyama O, Ohkubo K, Yotsuyanagi T
Research Laboratories, Bristol-Myers Squibb K. K., Saitama, Japan.
Chem Pharm Bull (Tokyo). 1992 Jun;40(6):1559-62. doi: 10.1248/cpb.40.1559.
The effects of dipotassium glycyrrhizinate (GLYK) on the dissolution behavior and bioavailability of amphotericin B (AMB) were investigated. The mixtures of AMB and GLYK were prepared at different molar ratios by lyophilization. Lyophilization resulted in amorphous AMB either alone or in the mixture. Dissolution rates of AMB of the mixtures were markedly faster than that of lyophilized AMB alone, which was followed by a decrease of dissolution. The initially-enhanced dissolution rate was likely to be due to the improvement of surface wettability of drug particles with GLYK rather than the amorphous state of AMB. A phase solubility study of AMB with GLYK indicated that the increasing solubility was caused by micellar solubilization. The in vitro release rate of AMB from suppositories containing the lyophilized mixtures was significantly accelerated by increasing the amount of GLYK. The rectal absorption of AMB from suppositories containing either the drug alone, a physical mixture or a lyophilized mixture was studied using rabbits. The absorption of the mixture (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum concentration-time curve (0-24 h) than that of lyophilized AMB alone. These results suggest that GLYK is useful for improving the dissolution property of AMB and the bioavailability of the drug incorporated in suppositories.
研究了甘草酸二钾（GLYK）对两性霉素B（AMB）溶解行为和生物利用度的影响。通过冻干法以不同摩尔比制备了AMB与GLYK的混合物。冻干后，AMB单独或在混合物中均呈无定形状态。混合物中AMB的溶解速率明显快于单独冻干的AMB，随后溶解速率下降。最初增强的溶解速率可能是由于GLYK改善了药物颗粒的表面润湿性，而非AMB的无定形状态。AMB与GLYK的相溶解度研究表明，溶解度的增加是由胶束增溶作用引起的。通过增加GLYK的量，显著加速了含冻干混合物栓剂中AMB的体外释放速率。使用兔子研究了含单独药物、物理混合物或冻干混合物的栓剂中AMB的直肠吸收情况。混合物（AMB/GLYK = 1/9）在血清浓度-时间曲线下面积（0 - 24小时）的吸收量比单独冻干的AMB约大35倍。这些结果表明，GLYK有助于改善AMB的溶解性能以及栓剂中药物的生物利用度。
