用混合粉碎法制备晶体药物与β-环糊精包合物

目的制备晶体药物与β-环糊精的包合物;分析包合物中药物的分散状态;考察最佳粉碎时间及形成包合物的适宜贮存湿度。方法采用混合粉碎法制备包合物;根据红外图谱、粉末X-射线衍射验证包合物的形成及最佳粉碎时间;通过升华失重确定包合物中药物分子的分散状态;变换贮存湿度考察包合物的聚结稳定性。结果制成的包合物为无定形结构,药物分子进入β-环糊精空穴中通过分子间氢键结合;包合物的分散度和粉碎时间有关,本系统的最佳粉碎时间为10 min;包合物中药物分子的状态受贮存时相对湿度的影响,在相对湿度低于75%下贮存时,包合物的分散状态未发生明显变化。结论采用混合粉碎法制备包合物,具有较好的稳定性;将晶体难溶性药物与β-环糊精混合粉碎可得到非晶质包合物,能有效地提高难溶性药物的溶解度。

Preparation of inclusion complex of crystalline drug with β-cyclodextrin by co-grinding

Objective To prepare inclusion complex of crystalline drug with β-cyclodextrin(β-CD) by co-grinding using benzoic acid as model drug and β-CD as inclusion carrier,explain the disperse state of the drug,and examine the effects of grinding time and suitable humidity of the storage on the formation of the inclusion complex.Methods The inclusion complex was prepared by co-grinding method.The formation and the best grinding time of the inclusion complex was confirmed according to infrared spectrum and power X-ray diffraction,the disperse state of the drug was determined by weightlessness,and the stability of inclusion complex was examined by changing storage humidity.Results After being co-grinded,the inclusion complex was in amorphous,drug was included in β-CD cavity,where the hydrogen bonds between the drug and β-CD might be formed.The dispersity of the inclusion complex in water was related to grinding time,optimal grinding time was 10 min.The movement state of the drug in the inclusion complex was influenced by storage humidity,and the disperse state has not change storing in relative humidity less than 75%.Conclusions The method for the preparation of inclusion complex using co-grinding method is effective and simple.The stabilities of the inclusion complexes are well.