马来酸噻吗洛尔磷脂复合物的制备及性质表征

Preparation and characterization of timolol maleate phospholipid complex

目的:制备马来酸噻吗洛尔磷脂复合物,以提高复合马来酸噻吗洛尔脂溶性。方法:采用溶剂挥发法制备磷脂复合物;以复合率为指标,采用单因素试验对物料比、复合时间、复合温度等进行优化筛选;并对最优处方制备的磷脂复合物用差示扫描量热法、傅里叶红外光谱、紫外光谱进行验证及性质表征。同时测定并比较马来酸噻吗洛尔及其磷脂复合物在蒸馏水及三氯甲烷中的溶解性。结果:以10 mL四氢呋喃为复合溶剂,马来酸噻吗洛尔与磷脂摩尔比为1∶2.5,水浴温度40℃,复合时间为3 h条件下,制备的马来酸噻吗洛尔磷脂复合物复合率最高,达(96.54±2.46)%。溶解度测定结果显示马来酸噻吗洛尔磷脂复合物在蒸馏水中溶解度明显低于马来酸噻吗洛尔,在三氯甲烷中溶解度明显高于马来酸噻吗洛尔(P<0.01)。结论:该实验将马来酸噻吗洛尔制备成磷脂复合物,增加了其脂溶性,有利于增加药物在皮肤黏膜的停留时间,延长药效。

Objective:To prepare the timolol maleate phospholipid complex for improving the liposolubility of timolol maleate.Methods:The timolol maleate phospholipid complex was prepared using solvent evaporation method.According to the recombination rate,the ratio of timolol maleate and soybean phosphatide,formation temperature and time were optimized and screened using single-factor experiment.The phospholipid complex prepared by optimal prescription was verified using differential scanning calorimetry,Fourier infrared spectroscopy and ultraviolet spectroscopy,and its property characterization was investigated.The dissolubilities of timolol maleate and its phospholipid complex in distilled water or chloroform were determined and compared.Results:The 10 mL tetrahydrofuran acted as the solvent,the molar ratio of timolol maleate to phospholipid was 1∶2.5,the water bath temperature was 40℃,and the formation time was 3 h,the recombination rate of timolol maleate phospholipid complex was the highest,which arrived at(96.54±2.46)%.The solubility test results showed that the solubility of timolol maleate phospholipid complex in distilled water was significantly lower than that of timolol maleate,and the solubility of timolol maleate phospholipid complex in chloroform was significantly higher than that of timolol maleate(P<0.01).Conclusions:Timolol maleate is prepared into phospholipid complex,which improves its lipid solubility,and is beneficial to increase the drugs residence time in skin and mucosa,and prolongs the efficacy.