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龙世玉, 刘秀, 秦杰峰, 王玲兰, 任超, 刘文龙.利格列汀片的制备及体内外评价[J].湖南中医药大学学报,2025,45(5):856-861[点击复制] |
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| 利格列汀片的制备及体内外评价 |
| 龙世玉,刘秀,秦杰峰,王玲兰,任超,刘文龙 |
| (湖南中医药大学药学院, 湖南 长沙 410208;株洲千金药业股份有限公司, 湖南 株洲 412000;湖南千金协力药业有限公司, 湖南 株洲 412000) |
| 摘要: |
| 目的 研制与原研制剂体外溶出一致、体内生物等效的利格列汀片仿制药。方法 制备利格列汀片，通过建立利格列汀片体外溶出高效液相色谱法检测方法，分别在pH 1.0盐酸溶液、pH 4.5醋酸钠盐缓冲溶液、pH 6.8磷酸二氢钾盐缓冲溶液、水介质中，测定利格列汀片自制制剂与原研制剂的累积溶出情况，采用非模型依赖方法（f2相似因子）计算自制制剂与原研制剂的溶出相似性；同时在健康成年受试者中进行单剂量、两制剂、两序列、两周期交叉试验设计的药代动力学研究，检测空腹及高脂餐后两种状态下受试者的血药浓度，计算药代动力学参数。结果 在4种溶出介质中，自制制剂与原研制剂的累积溶出曲线相似；药代动力学研究显示，空腹及餐后状态下，自制制剂与原研制剂的药代参数Cmax、AUC0-t的几何均值比值及其90%置信区间均在80.00%~125.00%范围内。结论 自制制剂与原研制剂体外溶出相似，且在药代动力学上生物等效。 |
| 关键词: 利格列汀片 溶出曲线 原研制剂 生物等效 高效液相色谱法 |
| DOI：10.3969/j.issn.1674-070X.2025.05.010 |
| 投稿时间：2025-02-16 |
| 基金项目:国家自然科学基金项目（81874344）；湖南省自然科学基金项目（2022JJ80048）。 |
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| Preparation and in vitro/in vivo evaluation of linagliptin tablets |
| LONG Shiyu, LIU Xiu, QIN Jiefeng, WANG Linglan, REN Chao, LIU Wenlong |
| (School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Zhuzhou Qianjin Pharmaceutical Co., Ltd., Zhuzhou, Hunan 412000, China;Hunan Qianjin Xieli Pharmaceutical Co., Ltd., Zhuzhou, Hunan 412000, China) |
| Abstract: |
| Objective To develop a generic linagliptin tablet with consistent in vitro dissolution and in vivo bioequivalence to the reference preparation. Methods Linagliptin tablets were prepared. A high performance liquid chromatography (HPLC)-based in vitro dissolution testing method was established to determine the cumulative dissolution of both the test and the reference preparations in four media: pH 1.0 hydrochloric acid solution, pH 4.5 sodium acetate buffer, pH 6.8 potassium dihydrogen phosphate buffer, and water. The dissolution similarity between the preparations was assessed using the model-independent approach (f2similarity factor). Concurrently, a single-dose, two-preparation, two-sequence, two-period crossover pharmacokinetic study was conducted in healthy adult subjects, with blood concentrations of linagliptin measured under fasting and high-fat post-meal conditions. Pharmacokinetic parameters were calculated. Results The cumulative dissolution profiles of the test and reference preparations were similar in all four dissolution media. Pharmacokinetic analysis revealed that under both fasting and fed conditions, the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for Cmax and AUC0-tt of the test preparation relative to the reference preparation fell entirely within the acceptance range of 80.00%-125.00%. Conclusion The test preparation of linagliptin tablets exhibited similar in vitro dissolution and pharmacokinetic bioequivalence to the reference preparation. |
| Key words: linagliptin tablets dissolution profile reference preparation bioequivalence high performance liquid chromatography |
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