The conventional oral dosage forms are not effective in dealing with chronopathological conditions, such as nocturnal asthma. Therefore, there is an unmet need to develop a delivery system that can deliver drug as per the chronopharmacology of the diseases. The purpose of the study is to use quality by design (QbD) technique and pulsatile principles for the development of Eudragit-coated dual release bilayer tablets. The dual layer consists of immediate release layer of fexofenadine HCl and sustained release layer of montelukast sodium. The quality target product profile of the formulation was developed, and the critical quality attributes were identified. Three-level, three-factor Box-Behnken design was used for the optimization of the bilayer tablets. Based on the design, a total of 13 formulation combinations (F1–F13 and M1–M13) were made having acceptable micromeritic properties. The developed immediate and sustained release layers were evaluated for physicochemical properties. Depending upon the value of the diffusion exponent, the Fickian diffusion mechanism is dominant among immediate and sustained release tablet layers. Response curve for immediate release layer showed that concentrations of sodium starch glycolate and sodium bicarbonate had a negative effect on disintegration time and a positive effect on drug release. For sustained release tablet layer, concentrations of HPMC E 5 LV and magnesium stearate had a significant effect on drug release. The ANOVA and diagnostic plots confirmed the significance and goodness of fit of the used model. Based on desirability plot values, optimized formulation was developed and coated with Eudragit coat. The coated bilayer tablet showed met the requirement of providing an immediate release during the first hour and a sustained release action for a period of more than 8 h after passing the gastric region. The formulation can be fruitful in curbing the menace of nocturnal asthma and providing a high degree of patient compliance as the patient will not have to wake up at night to take the medication.

中文翻译：

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非索非那定和孟鲁司特的优化调时双重释放双层片剂：设计，开发和体外评估的质量

传统的口服剂型不能有效地治疗诸如夜间哮喘的时间病理状况。因此，迫切需要开发一种可以按照疾病的时间药理学来输送药物的输送系统。这项研究的目的是利用设计质量（QbD）技术和搏动原理开发Eudragit包衣的双释放双层片剂。双层层由盐酸非索非那定的立即释放层和孟鲁司特钠的持续释放层组成。开发了制剂的质量目标产品概况，并确定了关键的质量属性。三级，三因素Box-Behnken设计用于优化双层片剂。根据设计，总共13种配方组合（F1-F13和M1-M13）具有可接受的微团性质。评价所形成的立即释放层和持续释放层的理化性质。根据扩散指数的值，菲克扩散机制在速释和缓释片剂层中占主导地位。速释层的响应曲线表明，乙醇酸淀粉钠和碳酸氢钠的浓度对崩解时间有负面影响，对药物释放有正面影响。对于缓释片剂层，HPMC E 5 LV和硬脂酸镁的浓度对药物释放具有显着影响。方差分析和诊断图证实了所用模型的拟合意义和良好性。根据期望图值，开发了优化配方并用Eudragit涂层涂覆。包衣的双层片剂显示满足在通过胃区域后的第一小时内立即释放和持续释放作用超过8小时的要求。该制剂可以有效地遏制夜间哮喘的威胁，并提供高度的患者依从性，因为患者不必在晚上醒来服用药物。