Dholariya Yatin N, Bansod Yogesh B, Vora Rahul M, Mittal Sandeep S, Shirsat Ajinath Eknath, Bhingare Chandrashekhar L
QAT Department, Marathwada Mitra Mandal's College of Pharmacy, Thergaon, Kalewadi, Pune, Maharashtra, India.
QA Department, Shri Ravatpura Sarkar Institute of Pharmacy, Kumhari, Raipur, Chhattisgarh, India.
Int J Pharm Investig. 2014 Apr;4(2):93-101. doi: 10.4103/2230-973X.133058.
The aim of the present study is to develop an optimize bilayered tablet using Hydrochlorothiazide (HCTZ) as a model drug candidate using quality by design (QbD) approach.
The bilayered tablet gives biphasic drug release through loading dose; prepared using croscarmellose sodium a superdisintegrant and maintenance dose using several viscosity grades of hydrophilic polymers. The fundamental principle of QbD is to demonstrate understanding and control of pharmaceutical processes so as to deliver high quality pharmaceutical products with wide opportunities for continuous improvement. Risk assessment was carried out and subsequently 2(2) factorial designs in duplicate was selected to carry out design of experimentation (DOE) for evaluating the interactions and effects of the design factors on critical quality attribute. The design space was obtained by applying DOE and multivariate analysis, so as to ensure desired disintegration time (DT) and drug release is achieved. Bilayered tablet were evaluated for hardness, thickness, friability, drug content uniformity and in vitro drug dissolution.
Optimized formulation obtained from the design space exhibits DT of around 70 s, while DR T95% (time required to release 95% of the drug) was about 720 min. Kinetic studies of formulations revealed that erosion is the predominant mechanism for drug release.
From the obtained results; it was concluded that independent variables have a significant effect over the dependent responses, which can be deduced from half normal plots, pareto charts and surface response graphs. The predicted values matched well with the experimental values and the result demonstrates the feasibility of the design model in the development and optimization of HCTZ bilayered tablet.
本研究的目的是采用质量源于设计（QbD）方法，以氢氯噻嗪（HCTZ）作为模型候选药物开发一种优化的双层片。
双层片通过负荷剂量实现双相药物释放；使用交联羧甲基纤维素钠（一种超级崩解剂）制备负荷剂量，并使用几种不同粘度等级的亲水性聚合物制备维持剂量。QbD的基本原理是证明对制药工艺的理解和控制，以便生产出具有持续改进广泛机会的高质量药品。进行了风险评估，随后选择重复的2（2）析因设计来进行实验设计（DOE），以评估设计因素对关键质量属性的相互作用和影响。通过应用DOE和多变量分析获得设计空间，以确保实现所需的崩解时间（DT）和药物释放。对双层片进行了硬度、厚度、脆碎度、药物含量均匀度和体外药物溶出度评估。
从设计空间获得的优化制剂的DT约为70秒，而药物释放T95%（释放95%药物所需的时间）约为720分钟。制剂的动力学研究表明，溶蚀是药物释放的主要机制。
从获得的结果得出结论，自变量对因变量反应有显著影响，这可以从半正态图、帕累托图和表面响应图中推断出来。预测值与实验值匹配良好，结果证明了设计模型在HCTZ双层片开发和优化中的可行性。
