Cao Feng, Guo Jianxin, Ping Qineng
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P.R. China.
Drug Dev Ind Pharm. 2005 Sep;31(8):747-56. doi: 10.1080/03639040500216220.
In an effort to improve the solubility of the insoluble drug scutellarin, a novel complexation of scutellarin with beta-cyclodextrin (beta-CD) was studied. Tetracomponent freeze-dried complex was prepared with scutellarin, beta-CD, Hydroxypropyl Methylcellulose (HPMC), and triethanolamine. To confirm complex formation, complex was characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction, and differential scanning calorimetry (DSC). Phase-solubility analysis suggested the soluble complexes having 1:1 stoichiometry. The beta-CD solubilization of scutellarin could be improved significantly by combining water-soluble polymer and pH adjuster. Comparing the binary, ternary solid systems with tetrary systems, tetracomponent freeze-dried complex showed the best effect of solubilization. A maximal solubility of scutellarin (23.65 mg/ml) was achieved with tetracomponent freeze-dried complex, up to 148-fold increase over scutellarin solubility in water, and the solubility of scutellarin is 15.35 microg/ml (up to 6-fold) in simulated gastric fluid.
为提高难溶性药物灯盏花素的溶解度,研究了灯盏花素与β-环糊精(β-CD)的新型络合物。用灯盏花素、β-CD、羟丙基甲基纤维素(HPMC)和三乙醇胺制备了四组分冻干复合物。为确认络合物的形成,通过傅里叶变换红外光谱(FT-IR)、粉末X射线衍射和差示扫描量热法(DSC)对络合物进行了表征。相溶解度分析表明形成的可溶性络合物化学计量比为1:1。通过结合水溶性聚合物和pH调节剂,灯盏花素的β-CD增溶作用可得到显著改善。将二元、三元固体系统与四元系统进行比较,四组分冻干复合物显示出最佳的增溶效果。四组分冻干复合物使灯盏花素的最大溶解度达到23.65 mg/ml,比灯盏花素在水中的溶解度提高了148倍,在模拟胃液中灯盏花素的溶解度为15.35 μg/ml(提高了6倍)。