尼扎替丁胃漂浮缓释片的制备与体外评价

摘要

目的 制备尼扎替丁胃漂浮缓释片, 并评价其体外释放度.方法 使用失效模式效应分析工具鉴定影响尼扎替丁胃漂浮缓释片质量的潜在风险因素, 并通过Plackett-Burman实验设计筛选出关键性因素, 最终以羟丙甲纤维素 (HPMC K15M) 、山嵛酸甘油酯和碳酸氢钠用量作为考察因素, 以尼扎替丁胃漂浮缓释片的漂浮延迟时间和在不同时间点的药物释放度作为评价指标, 使用Box-Behnken实验设计优化处方, 并考察尼扎替丁胃漂浮缓释片的体外释药行为.结果 筛选实验结果表明碳酸氢钠用量可显著影响尼扎替丁胃漂浮缓释片的漂浮延迟时间, HPMC K15M和山嵛酸甘油酯用量可显著影响药物释放速率;最终得到尼扎替丁胃漂浮缓释片的处方设计空间;体外释放度实验显示, 制备的尼扎替丁胃漂浮缓释片漂浮延迟时间仅为0.89min, 在24h内药物释放平缓、完全.结论 本研究通过联合使用Plackett-Burman和Box-Behnken实验设计优化得到的尼扎替丁胃漂浮缓释片处方漂浮延迟时间较短, 药物释放符合质量要求, 可进一步进行放大研究.%Objective To prepare nizatidine gastro-retentive sustained release (Nizatidine-GRSR) tablets and evaluate their in vitro dissolution.Methods Failure Mode Effect Analysis (FMEA) was used to identify the potential risk factors that affected the quality of Nizatidine-GRSR tablets.The key factors were screened by Plackett-Burman experiment design.Finally, the amounts of sodium bicarbonate, hydroxypropyl methylcellulose (HPMC K15 M) and glyceryl behenate were used as investigation factors, while the floating lag time and drug dissolution at different time points were taken as evaluation indexes.The formulation of Nizatidine-GRSR tablets was optimized using Box-Behnken experiment design.The in vitro dissolution behavior of Nizatidine-GRSR tablets was evaluated.Results The Plackett-Burman experimentdesign showed that the amount of sodium bicarbonate significantly affected the floating lag time, while HPMC K15 Mand glyceryl behenate significantly affected the drug dissolution rate.The design space of Nizatidine-GRSRO tablets was determined by Box-Behnken experiment design.In vitro dissolution showed that the floating lag time of Nizatidine-GRSR tablets was only 1.5 min, and the drug was dissolved slowly and completely within 24 h.Conclusion The formulation of Nizatidine-GRSR tablets optimized by the combination of Plackett-Burman experiment design and Box-Behnken experiment design has a shorter floating lag time and the in vitro dissolution meets the quality requirements.More amplification studies need to be conducted.