Sridevi S, Chauhan A S, Chalasani K B, Jain A K, Diwan P V
Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad, India.
Pharmazie. 2003 Nov;58(11):807-10.
The virtual insolubility of gliquidone in water results in poor wettability and dissolution characteristics, which may lead to a variation in bioavailability. To improve these characteristics of gliquidone, binary systems with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were prepared by classical methods such as physical mixing, kneading, co-evaporation and co-lyophilization. The solid state interaction between the drug and HP-beta-CD was assessed by evaluating the binary systems with X-ray diffraction, differential scanning calorimetry and IR- spectroscopy. The results establish the molecular encapsulation and amorphization of gliquidone. The phase solubility profile of gliquidone in aqueous HP-beta-CD vehicle resulted in an A(L) type curve with a stability constant of 1625 M(-1). The dissolution rate of binary systems was greater than that of pure drug and was significantly higher in the case of co-lyophilized and co-evaporated systems. Upon oral administration, [AUC]-alpha was significantly higher in case of co-lyophilized (2 times) and co-evaporated systems (1.5 times) compared to pure drug suspension while other binary systems showed only a marginal improvement. The study ascertained the utility of HP-beta-CD in enhancing the oral bioavailability of gliquidone, and points towards a strong influence of the preparation method on the physicochemical properties.
格列喹酮在水中实际上不溶，导致其润湿性和溶解特性较差，这可能会导致生物利用度的变化。为改善格列喹酮的这些特性，采用物理混合、捏合、共蒸发和共冻干等经典方法制备了与羟丙基-β-环糊精（HP-β-CD）的二元体系。通过X射线衍射、差示扫描量热法和红外光谱法对二元体系进行评估，以确定药物与HP-β-CD之间的固态相互作用。结果证实了格列喹酮的分子包封和无定形化。格列喹酮在HP-β-CD水性载体中的相溶解度曲线呈现A(L)型，稳定常数为1625 M(-1)。二元体系的溶解速率大于纯药物，在共冻干和共蒸发体系中显著更高。口服给药后，与纯药物混悬液相比，共冻干体系（2倍）和共蒸发体系（1.5倍）的[AUC]-α显著更高，而其他二元体系仅显示出轻微改善。该研究确定了HP-β-CD在提高格列喹酮口服生物利用度方面的效用，并指出制备方法对物理化学性质有很大影响。
