那格列奈—2-羟丙基-β-环糊精包合物的制备及其理化性质

目的考察2-羟丙基-β-环糊精(HPCD)对那格列奈的增溶作用;研究那格列奈-HPCD包合物的制备工艺;考察包合物的光谱表征及包合物胶囊的体外释放行为。方法考察不同pH值、不同浓度的HPCD对那格列奈的增溶作用;通过研磨法和冷冻干燥法制备包合物;采用X-射线衍射及差示扫描热量法2种技术手段确证包合物的形成;在不同介质中考察不同方法制备的包合物的溶出度。比较不同环糊精用量比例的包合物、混合物及普通原料药的溶出度。结果不同pH条件下HPCD对那格列奈的增溶作用不同;差热分析及X-射线衍射证明了那格列奈与HPCD形成了包合物;那格列奈-HPCD包合物的水溶性好,在水介质中溶出度较高,在那格列奈与HPCD摩尔比为1∶2的情况下,冷冻干燥法制备的包合物,在pH 1.0的条件下体外溶出度达到100%,研磨法制备的包合物溶出度大于85%,而原料药溶出度仅为20%,显示出了那格列奈包合后的优势。结论包合物的光谱表征同那格列奈有明显不同;经包合后那格列奈的溶解度明显增大;用包合物制的胶囊体外溶出速度快,溶出度高。

Preparation and physico-chemical property of nateglinide-HPCD inclusion complexes

Objective To investigate the solubilization of nateglinide by HPCD, prepare its HPCD inclusion complexes and study the apparent characteristics of their spectrum and in vitro release profile. Methods Solubilization of nateglinide was investigated in different concentration of HPCD phosphate buffer with various pH. The nateglinide-HPCD inclusion complexes were prepared by using grinding and freeze-drying methods and evaluated by X-ray and differential scanning calorimetry. The dissolution rates of inclusion complexes were determined in different medium. Results Solubilization of nateglinide by HPCD was different in various pH conditions. Nateg linide was proved to be inclusived by HPCD since the characteristic peaks of nateglinide were disappeared through the measurement of X-ray diffraction and differential scanning calorimetry. Nateglinide-HPCD inclusion complexes have considerable water-solubility and the water dissolution rate was very high. The dissolution rate of nateglinide by the method of freeze drying was 100 % in the medium of the pH 1.0 buffer, and the dissolution rate of nateglinide by grinding was more than 85 96. Howerer, the dissolution of free nateglinide was less than 20 %. Conclusions The solubility and dissolution of nateglinide were increased throngh the formation of inclusion complex with HPCD.