羟丙基-β-环糊精对兰索拉唑的增溶作用及其包合物的制备

Solubilization of lansoprazole using hydroxypropyl-β-cyclodextrin and preparation of their inclusion complexes

目的研究羟丙基-β-环糊精(HP--βCD)对难溶性药物兰索拉唑(LPZ)的包合作用。方法绘制相溶解度图,考察pH变化、碳酸氢钠的加入对LPZ的增溶作用。采用共蒸发法(CE)和喷雾干燥法(SD)按照LPZ∶HP--βCD量比为1∶1或1.0∶1.5的比例制备LPZ/HP--βCD包合物,测定其溶出度,并利用差示扫描量热法(DSC)和傅立叶红外光谱法(FTIR)对SD法制备的包合物进行结构表征。结果在pH 11条件下,HP-β-CD与NaHCO3对LPZ的协同增溶效果最好。体外溶出实验表明:CE法和SD法制备的包合物溶出均优于LPZ与HP-β-CD的物理混合物。结论HP--βCD能明显提高LPZ的溶解度和溶出度。

Objective To investigate the complexation of lansoprazole （LPZ） with hydroxylpropyl-β-cyclo- dextrin（ HP-β-CD）. Methods The phase solubility diagrams of LPZ versus HP-β-CD were plotted for analy- sing the influence of buffer pH and the presence of NaHCO3 on HP-β-CD complexation of LPZ. Solid inclu- sion complexes of LPZ/HP-β-CD were prepared in 1： 1 or 1.0：1.5 mole ratios with the addition of NaHCO3 by the co-evaporating method（CE） and spray drying method（ SD）, the characteristics of which were studied preliminarily by in vitro dissolution test, differential scanning calorimetry （DSC）and fourier transform infrared（FTIR） spectroscopy. Results Total drug solubility was evidently enhanced under pH 11 by combined using HP-β-CD and NaHCO3. In vitro study, the complexes prepared by CE or SD both enhanced the dissolution rate and accumulate dissolution of LPZ in pH 6.8 buffer solution comparing with LPZ and the physical mixture of LPZ and HP-β-CD. Conclusions The solubility and dissolution rate of LPZ are improved by HP-β-CD complexation obviously.