经鼻用盐酸苯海索脂质体的处方工艺研究

Investigation on Formulation and Preparation Process of Trihexyphenidyl Hydrochloride Liposomes for Nasal Administration

首先以包封率、粒径及ζ电位为指标筛选经鼻用盐酸苯海索脂质体的制备方法;再通过单因素试验和星点设计-效应面法,以包封率为指标优化脂质体的处方工艺。结果显示,优化脂质体采用乙醇注入法制备,处方中卵磷脂与胆固醇质量比为6.02、卵磷脂与药物比为41.96、有机相与水相比例为1∶1,成膜温度为50 ℃,30 ℃保温30 min。所得优化脂质体的粒径(73.23±0.98)nm,ζ电位(6.29±0.60)mV,包封率为(91.49±2.77)%,载药量(1.69±0.08)%。在pH 7.4磷酸盐缓冲液中12 h累积释放率达(84.1±1.9)%,符合Higuchi模型。

In this paper,the preparation methods for trihexyphenidyl hydrochloride liposomes for nasal administration were firstly screened with encapsulation efficiency,particle size and ζ potential as the indexes,then the formulation and process of the liposomes were optimized by single factor test and central composite design-response surface methodology with encapsulation efficiency as the index.The results showed that the optimal liposomes were prepared at film forming temperature of 50 ℃ and incubated at hydration temperature of 30 ℃ for 30 min by ethanol injection method with the mass ratio of lecithin to cholesterol of 6.02,the lecithin-to-drug ratio of 41.96,and organic-water phase volume ratio of 1∶1.The particle size,ζ potential,encapsulation efficiency and drug loading of the prepared liposomes were (73.23±0.98)nm,(6.29±0.60)mV,(91.49±2.77)% and (1.69±0.08)%,respectively.The cumulative release at 12 h of trihexyphenidyl hydrochloride from the liposomes was (84.1±1.9)% in pH 7.4 phosphate buffer.The release data fit well to a Higuchi model.