PDF(Pubmed)
Abstract：
The main goal of the study was to improve the compliance and convenience of patients by designing and development of an immediate release (IR) fixed-dose combination (Clopidogrel bisulphate and Aspirin) tablets. The proposed combination product utilizes Clopidogrel to protect the moisture-sensitive aspirin component, enhancing its stability against atmospheric conditions. Response-surface approach (Design Expert vs. 13) was used to generate this IR tablet by calculating the right composition of independent variables such as Microcrystalline cellulose 102, pregelatinized starch and Hydroxypropyl cellulose. 32 factorial design was used to estimate the effects of these independent variables on the responses of dependent variables (disintegration & friability) and constructed a total of nine (9) formulations. Pre and Post formulation, quality control parameters were investigated as per pharmacopeia. A systematic approach was used for the optimization process and a prototype checkpoint batch (CPB) based on the better contrast of independent variables was prepared. In vitro analysis of formulations was carried out to estimate the responses. Friability was found in the range of 0.088-1.076%w/w, except F1 = 1.076 all are within limits (NMT 1.0%). Disintegration time was recorded 7.3 ± 1.20 as lower and 24.5 ± 1.63 min was the highest. The release of drugs from their dosage form was fast and rapid, for clopidogrel after 15min was 70.42-96.82% with SD ± 8.71 and aspirin was 69.88-91.49% in 15 min with SD ± 6.41, all the tablets were released more than 80% in 20 min. The stability outcomes of CPB tablets after 15 days of stress study (60 ± 2°C and 75 ± 5%) indicated good compatibility and stability of APIs with excipients. It was concluded that the direct compression method can be preferred to prepare a combination product with cost-effectiveness. It was also concluded that the proposed methodology could increase Aspirin\'s stability and allow for an aqueous coating system to finish the product with a film coating. By using Design Expert software, the best composition of the formulation can be selected and optimized in a short period of time with minimum trial and errors. The results also demonstrated that the use of a fixed-dose combination tablet instead of the individual is expected to be more convenient to patients and thus improves patient compliance and decreases the occurrence of adverse effects and side effects.
摘要：
该研究的主要目标是通过设计和开发速释（IR）固定剂量组合（硫酸氢氯吡格雷和阿司匹林）片剂来提高患者的依从性和便利性。拟议的组合产品利用氯吡格雷来保护对水分敏感的阿司匹林成分，增强其对大气条件的稳定性。响应面方法(设计专家与13)用于通过计算独立变量如微晶纤维素102、预糊化淀粉和羟丙基纤维素的正确组成来产生该IR片剂。使用32阶乘设计来估计这些自变量对因变量（崩解性和脆性）的响应的影响，并构造了总共九（9）个配方。制定前和制定后,质量控制参数按照药典进行研究。在优化过程中使用了系统方法，并根据自变量的更好对比准备了原型检查点批次（CPB）。进行制剂的体外分析以估计反应。脆性在0.088-1.076%w/w范围内，除F1=1.076外，均在限值范围内（NMT1.0%）。崩解时间较低为7.3±1.20，最高为24.5±1.63分钟。药物从它们的剂型中快速释放，氯吡格雷在15min后为70.42-96.82%，SD±8.71，阿司匹林在15min内为69.88-91.49%，SD±6.41，所有片剂在20min内释放超过80%。CPB片剂在压力研究15天后的稳定性结果(60±2°C和75±5%)表明API与赋形剂的良好相容性和稳定性。结论直接压片法可以优选制备具有成本效益的组合产品。还得出结论，所提出的方法可以提高阿司匹林的稳定性，并允许水性涂层系统用薄膜涂层完成产品。通过使用DesignExpert软件，可以在短时间内以最少的试验和错误选择和优化制剂的最佳组成。结果还表明,使用固定剂量的组合片剂代替个体预期对患者更方便,因此改善了患者的依从性并减少了不良作用和副作用的发生。
