赖诺普利迟释型缓释片的制备及其体外释放研究

Study on Preparation and in vitro Release Rate of Lisinopril Delayed-onset Sustained-release Tablet

目的:制备赖诺普利迟释型缓释片,并对其体外释放度进行测定。方法:以羟丙甲纤维素(HPMC)为片芯骨架材料,乙基纤维素为阻滞材料,聚乙二醇(PEG)为致孔剂,利用包衣技术制备赖诺普利迟释型缓释片。以6、10、16、22 h的累积释放度(Q6 h、Q10 h、Q16 h、Q22 h)为指标,采用正交试验优化HPMC型号、用量和PEG用量,并进行验证。比较自制赖诺普利迟释型缓释片、自制赖诺普利缓释片芯和市售赖诺普利片在0.1 mol/L盐酸溶液中22 h内的Q。结果:最优处方为HPMC型号为K100M,占片芯质量比例为35%,PEG比例为40%,即600片赖诺普利迟释型缓释片中含赖诺普利18 g、乳糖54 g、HPMC(K100M)48 g、PEG 1.6 g、10%聚维酮乙醇溶液适量、硬脂酸镁1%、微粉硅胶1%、乙基纤维素2.4 g;所制3批赖诺普利迟释型缓释片的Q6 h、Q10 h、Q16 h、Q12 h的均值分别为11.17%、29.55%、62.38%、82.63%。自制赖诺普利缓释片芯Q10 h达80%以上,Q14 h为95.60%;市售赖诺普利片的Q5 min即达80%以上,Q1 h为97.95%;自制赖诺普利迟释型缓释片Q6 h仅为13.97%,Q22 h为84.12%,其释放特征符合零级动力学模型。结论:成功制得体外延迟4 h释放药物,并可缓慢释放22 h的赖诺普利迟释型缓释片。

OBJECTIVE： To prepare Lisinopril delayed-onset sustained-release tablet, and to determine the in vitro release rate. METHODS： Lisinopril delayed-onset sustained-release tablet was prepared by coating technology using hydroxypropyl methyl cellulose （HPMC） as matrix material, ethyl cellulose as retarding material and polyethylene glycol （PEG） as porous agent. With 6, 10, 16 and 22 h accumulative release rate （Q6h, Q10h, Q16h, Q22h） as index, the orthogonal test was used to optimize the type and the amount of HPMC and the amount of PEG, and the test was used to verify the preparation process. Self-made Lisinopril delayed-on- set sustained-release tablet, self-made Lisinopril sustained-release tablet core and commercially available Lisinopril tablet were compared about Q22h in 0.1 mol/L HC1. RESULTS： The optimized technology was HPMC K100M with ratio in tablet core quality of 35% and polyethylene glycol of 40%, that was 600 tablets contained lisinopril 18 g, lactose 54 g, HPMC （K100M） 48 g, PEG 1.6 g, appropriate amount of clcoholic solution of 10% polyvinylpyrrolidone, magnesium stearate 1%, gum acacia 1%, ethyl cellulose 2.4 g. The average value of Q6 h, Ql0 h, Q16h, Q22h of 3 batches of Lisinopril delayed-onset sustained-release tablets were respectively 11.17 %, 29.55 %, 62.38 %, 82.63 %. Q10h of self-made Lisinopril sustained-release tablet core was more than 80 %, and Q14h of it was 95.60% ; Q5 mia of commercially available Lisinopril tablet was more than 80% and Q1h of it was 97.95% ; Q6h of self-made Lisinopril delayed-onset sustained-release tablet was just 13.97%, and Q22h of it was 84.12%. Its release characteristics conformed to zero-order kinetic model. CONCLUSIONS： Lisinopril delayed-onset sustained-release tablet, which can delay drug release for 4 h and release slowly for 22 h, is prepared successfully.