盐酸曲美他嗪脉冲释放片治疗晨发性心绞痛症状：双重优化、特征描述和药代动力学评价。
Trimetazidine Dihydrochloride Pulsatile-Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation.
机构信息
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr City, Po. Box 11829, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Po. Box 11562, Cairo, Egypt.
出版信息
Curr Drug Deliv. 2021;18(8):1182-1196. doi: 10.2174/1567201818666210212095932.
OBJECTIVE
This research work aimed to target the early morning peak symptoms of chronic stable angina through formulating antianginal drug, Trimetazidine (TMZ) in a pulsatile-release tablet.
METHODS
The core formulae were optimized using 22 .31 factorial design to minimize disintegration time (DT) and maximize drug release after 5 minutes (Q5min). Different ratios of Eudragit S100 and Eudragit L100 were used as a coating mixture for the selected core with or without a second coating layer of hydroxypropyl methylcellulose (HPMC E50). The different formulation variables were statistically optimized for their effect on lag time and drug release after 7 hours (Q7h) using BoxBehnken design. The optimized formula (PO) was subjected to stability study and pharmacokinetic assessment on New Zealand rabbits.
RESULTS
The optimal core (F8) was found to have 1.76 min disintegration time and 61.45% Q5min PO showed a lag time of 6.17 h with 94.80% Q7h and retained good stability over three months. The pharmacokinetics study confirmed the pulsatile-release pattern with Cmax of 206.19 ng/ml at 5.33 h (Tmax) and 95.85% relative bioavailability compared to TMZ solution.
CONCLUSION
Overall pulsatile-release tablets of TMZ successfully released the drug after a desirable lag time, providing a promising approach for early morning anginal symptoms relief.
目的
通过将抗心绞痛药物曲美他嗪（TMZ）制成脉冲释放片剂，靶向治疗慢性稳定性心绞痛的清晨高峰症状。
方法
采用 22.31 析因设计优化核心配方，以最小化崩解时间（DT）并最大化 5 分钟后药物释放（Q5min）。使用不同比例的 Eudragit S100 和 Eudragit L100 作为所选核心的包衣混合物，或在其外部再包一层羟丙甲纤维素（HPMC E50）。使用 BoxBehnken 设计对不同的配方变量进行统计学优化，以研究其对 7 小时后滞后时间和药物释放（Q7h）的影响。对优化的配方（PO）进行了稳定性研究和新西兰兔的药代动力学评估。
结果
发现最优核心（F8）的崩解时间为 1.76 分钟，PO 的 Q5min 达到 61.45%。PO 显示滞后时间为 6.17 小时，Q7h 为 94.80%，在三个月内保持良好的稳定性。药代动力学研究证实了脉冲释放模式，Cmax 为 206.19ng/ml，达峰时间（Tmax）为 5.33 小时，与 TMZ 溶液相比具有 95.85%的相对生物利用度。
结论
TMZ 的脉冲释放片剂在理想的滞后时间后成功释放药物，为缓解清晨心绞痛症状提供了一种有前途的方法。
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