星点设计-效应面法优化盐酸普萘洛尔凝胶的处方及透皮吸收研究

Formulation optimization of propranolol hydrochloride gels by central composite design-response surface methodology and in vitro transdermal absorption test

目的:制备用于治疗婴幼儿血管瘤的新制剂盐酸普萘洛尔凝胶,并对其处方进行优化。方法:以泊洛沙姆P407为凝胶基质,以氮酮、丙二醇为促透剂,制备盐酸普萘洛尔凝胶。采用Franz扩散池对凝胶进行体外透皮试验,以体外累积透皮渗透量为指标,采用星点设计-效应面法优选处方中氮酮和丙二醇的最佳配比,并对最优处方进行验证。结果:盐酸普萘洛尔凝胶促透剂的最优配比为氮酮4%,丙二醇5%,12 h的累积透皮渗透量为1 377.81μg·cm-2。结论:通过星点设计-效应面法优选得到的盐酸普萘洛尔凝胶处方,性质稳定,质量可控,可为该药治疗婴幼儿血管瘤提供一种新的给药途径。

Objective： To optimize the formulation of propranolol hydrochloride gels for the treatment of infantile hemangioma. Methods： Poloxamer P407 was used as gel matrix with azone and propylene glycol as transdermal permeation enhancers for the preparation of propranolol hydrochloride gels. Central composite designresponse surface methodology was applied to optimize the proportions of azone and propylene glycol in the prescription according to the cumulative amount of permeation in vitro measured by Franz diffusion. The optimal prescription was verified finally. Results： 4% azone and 5% propylene glycol were the optimal transdermal permeation enhancers of propranolol hydrochloride gels. The cumulative amount of permeation in vitro at 12 h was up to 1 377. 81 μg·cm-2.Conclusion： The prescription of propranolol hydrochloride gels optimized by central composite design-response surface methodology is stable and the quality of the product is controllable. So it can provide a new administration route of propranolol in the treatment of infantile hemangiomat.