Rasool Fatima, Ahmad Mahmood, Murtaza Ghulam, Khan Haji M S, Khan Shujaat Ali
Faculty of Pharmacy and Alternative Medicines, Islamia University of Bahawalpur, Bahawalpur-63100, Pakistan.
Acta Pol Pharm. 2012 Mar-Apr;69(2):347-53.
Metoprolol, a cardioselective β-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency. Metoprolol tartrate loaded Eudragit FS microparticles were formulated using solvent evaporation technique by varying polymer contents and then compressing into tablets. The dissolution test was performed in simulated gastrointestinal fluid. All tabletted microparticles were tested for stability after storage in accelerated conditions. As a result of various analytical tests like FTIR, XRD and DSC analyses, drug was found stable in the microparticles. Metoprolol tartrate loaded Eudragit FS tabletted microparticles were stable in accelerated storage conditions. The release behavior of pH-dependent formulations was affected by the dissolution medium pH and the concentration of polymer used. There was a decrease in drug release rate with the increase in polymer concentration. In vitro drug release data (except test formulation F3) were best fitted to zero order model, which indicated the controlled release nature of formulation, while the Korsmeyer-Peppas model explored that drug release occurred according to case II relaxation transport mechanism (n > 0.89). Based on the results, it can be concluded that Eudragit FS is a suitable polymer to design pH dependent microparticles using solvent evaporation technique for the release of drug in colon and T2 can be considered as an optimum formulation on the basis of model independent (f2 test) kinetic interpretation of dissolution results (f2 < 50 for T2 versus reference).
美托洛尔是一种心脏选择性β受体阻滞剂，口服后在结肠中吸收良好，由于广泛的首过效应，平均消除半衰期为3小时，生物利用度为50%，因此旨在开发其缓释剂型以减少给药频率。采用溶剂蒸发技术，通过改变聚合物含量，制备了载有酒石酸美托洛尔的Eudragit FS微粒，然后压制成片剂。在模拟胃肠液中进行溶出试验。所有压制的微粒在加速条件下储存后进行稳定性测试。通过傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）和差示扫描量热法（DSC）等各种分析测试，发现药物在微粒中稳定。载有酒石酸美托洛尔的Eudragit FS压制微粒在加速储存条件下稳定。pH依赖性制剂的释放行为受溶出介质pH值和所用聚合物浓度的影响。随着聚合物浓度的增加，药物释放速率降低。体外药物释放数据（测试制剂F3除外）最符合零级模型，这表明制剂具有控释性质，而Korsmeyer-Peppas模型表明药物释放是根据II型松弛转运机制发生的（n>0.89）。根据结果可以得出结论，Eudragit FS是一种合适的聚合物，可采用溶剂蒸发技术设计pH依赖性微粒，用于结肠中药物的释放，基于溶出结果的模型无关（f2测试）动力学解释（T2与参比制剂相比f2<50），T2可被视为最佳制剂。
