盐酸普萘洛尔凝胶的制备与处方优化

Preparation and Formulation Optimization of Hydrochloride Propranolol Gel

目的：为了避免口服给药可能发生的肝脏首关效应及全身不良反应,制备盐酸普萘洛尔凝胶,并进行处方优化。方法：以水溶性氮酮为渗透促进剂,羟丙甲纤维素K4M为凝胶基质制备盐酸普萘洛尔凝胶。单因素考察法筛选盐酸普萘洛尔凝胶处方中的主药浓度、p H、保湿剂等;以8 h的累积渗透量和稳态渗透速率为指标,采用星点设计法对水溶性氮酮和羟丙甲纤维素K4M的浓度进行优化,并对最优处方进行验证。结果：最优处方为盐酸普萘洛尔3 g、水溶性氮酮1.64 g、丙二醇10 g、羟丙甲纤维素K4M2.61 g、甘油10 g、羟苯乙酯0.1 g,加水至100 g,p H为5.0-6.5;所制凝胶8 h的累积渗透量和稳态渗透速率分别为290.10μg/cm2、36.90μg/（cm2·h）。结论：成功制得渗透效果较好的盐酸普萘洛尔凝胶。

OBJECTIVE： To prepare Hydrochloride propranolol gel, and to optimal the formulation in order to aviod first pass effect and systemic ADR result from oral administration. METHODS： Hydrochloride propranolol gel was prepared using water-soluble azone as penetration enhancer and HPMC K4M as matrix. The concentration of hydrochloride propranolol, pH and moisturizing agents were screened by single factor investigation. The concentration of penetration enhancer water-soluble azone and HPMC K4M were optimized by central composite design using 8 h accumulative transdermal amount and steady penetration rate as index. The optimal formulation was validated. RESULTS： The optimal formulation was as follows： hydrochloride propranolol 3 g, water-soluble azone 1.64 g, propylene glycol 10 g, HPMC K4M 2.61 g, glycerol 10 g, ethyl hydroxybenzoate 0.1 g, add water to 100 g, pH 5.0-6.5. 8 h accumulative transdermal amount and steady penetration rate of prepared gel were 290.10 μg/cm2 and 36.90 μg/（cm2.h）. CONCLUSIONS ： Hydrochloride propranolol gel with good penetration propriety has been prepared successfully.