Nouh A T, Abd El-Gawad A H, Guda T K
Pharmaceutics Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Drug Discov Ther. 2010 Apr;4(2):93-9.
Controlled release tablets containing 50 mg diclofenac sodium (DS) and 40% mastic with other natural additives were prepared. Drug release was examined and stability was studied using non-isothermal and isothermal thermogravimetric analysis (TGA). The bioavailability of two controlled release tablet formulations was studied and compared to that of commercial tablets, and rabbit stomachs were also histologically examined 24 h after administration of the various tablets. Additives of pectin and sodium alginate indicated the controlled release profile of the drug. Non-isothermal TG revealed two stages of thermal decomposition for all formulations. Isothermal TG revealed that degradation of the drug in the tablet formulations follows first-order kinetics. The obtained degradation rate constants at various temperatures were plotted according to the Arrhenius equation. The degradation rate constant at 25°C was determined and used in estimation of shelf life. The obtained shelf lives of all formulations ranged from 3.38-4.92 years. In comparative studies with commercial tablets, the bioavailability of the drug from the two formulated tablets had no statistically significant difference in terms of the AUC and produced prolonged blood levels of DS with a delayed peak. The two controlled release tablet formulations resulted in no histological alterations in the stomach in terms of mucous surface cells and glands; in comparison, commercial tablets resulted in a disrupted mucous layer, necrotic ulcerations, hemorrhaging, and inflammatory cell infiltration along the base of the gastric glands.
制备了含有50毫克双氯芬酸钠（DS）和40%乳香以及其他天然添加剂的控释片。采用非等温及等温热重分析（TGA）对药物释放进行了检测，并对稳定性进行了研究。研究了两种控释片制剂的生物利用度，并与市售片剂进行比较，还在给予各种片剂24小时后对兔胃进行了组织学检查。果胶和海藻酸钠添加剂显示出药物的控释特性。非等温TG显示所有制剂均有两个热分解阶段。等温TG显示片剂制剂中药物的降解遵循一级动力学。根据Arrhenius方程绘制了不同温度下获得的降解速率常数。测定了25°C时的降解速率常数并用于估计保质期。所有制剂的保质期为3.38 - 4.92年。在与市售片剂的对比研究中，两种制剂片剂的药物生物利用度在AUC方面无统计学显著差异，且使DS血药浓度延长，峰期延迟。两种控释片制剂在胃黏膜表面细胞和腺体方面未导致组织学改变；相比之下，市售片剂导致黏液层破坏、坏死性溃疡、出血以及胃腺底部的炎性细胞浸润。
