茶碱缓释片的制备及与参比制剂的体外溶出相似性评价

黎德南 韦伟宁

[摘要]目的阐述茶碱缓释片的制备方法及与参比制剂的释放度相似性评价。方法本研究以茶碱为原料，以羟乙基纤维素为骨架材料、十六十八醇为阻滞剂、聚维酮 K30为粘合剂，滑石粉、硬脂酸镁为润滑剂，采用湿法制粒后压片的工艺，制得茶碱缓释片。参照 JP 中茶碱缓释片溶出度项下的检测方法，分别以4种溶出介质，检测自研制剂与参比制剂的释放度，以评价其体外溶出相似性。结果自研制剂的体外释放速度恒定，与参比制剂比较，溶出曲线相似因子 f2>50，具有体外溶出相似性。结论自研制剂处方、工艺对确保茶碱缓释片与参比制剂生物等效有重大意义，可提高茶碱缓释片临床用药的安全性与有效性。

[关键词]茶碱;缓释片;参比制剂;释放度;生物等效性

[中图分类号] R284.1  [文献标识码] A   [文章编号]2095-0616（2021）23-0082-04

Preparation  of theophylline  extended -release  tablets  and evaluation of in vitro dissolution similarity with the reference preparation

LI  De'nan    WEI  Weining

1. College of Pharmacy， Guilin Life and Health Career Technical College， Guangxi， Guilin 541100， China;2. Guangxi Hongshantang Biotechnology Co.， Ltd.， Guangxi， Nanning 530000， China

[Abstract] Objective To describe the preparation method of theophylline extended-release tablets and the evaluation of dissolution similarity with the reference preparation. Methods This research described that the theophylline extended-release tablets were prepared by taking theophylline as raw material， hydroxyethyl cellulose as the backbone material， cetostearyl alcohol as the blocking agent， povidone K30 as the binder， talc and magnesium stearate as the lubricant， and adopting the process of wet granulation followed by tablet compression. With reference to the testing method under the Dissolution of theophylline extended-release tablets in JP， the in vitro dissolution similarity was evaluated by testing the dissolution rate of the self-made preparation and the reference preparation using four dissolution media， respectively. Results The in vitro dissolution rate of the self-made preparation remains constant. The dissolution curve similarity factor f2 between the reference preparation and the self-made preparation was more than 50， with similar in vitro dissolution. Conclusion The prescription and process of the self-made preparation are of great significance to ensure the bioequivalence of theophylline extended-release tablets and the reference preparation， and can improve the safety and effectiveness of clinical medication of theophylline extended-release tablets.

[Key words] Theophylline; Extended-release tablets; Reference preparation; Dissolution rate; Bioequivalence

茶堿（theophylline）是一种平滑肌松弛药。临床上主要用于治疗哮喘和哮喘性支气管炎。成人用药后半衰期为5～6 h，儿童平均为3.5 h。茶碱治疗血药浓度较窄（5～20μg/ml），个体差异较大，清除率和半衰期也因人而异。普通茶碱片给药后血药浓度容易出现“峰谷”现象，引起头痛、恶心、失眠、抽筋及过敏等毒副作用，茶碱缓释片可减少给药次数，有效避免血药浓度的“峰谷”现象，减轻给药后的毒副作用[1]。

部分已上市口服固体仿制制剂安全无效[2-3]，甚至有的制剂发生安全事件，故2016年3月国家正式开启仿制药质量与疗效一致性评价工作[4]。目前，上市的国产茶碱缓释片仿制药的批准文号有40个[5]，均有待进行一致性评价。本……