The main objective of the present study was to develop and optimize an effervescent tablet of levetiracetam, an antiepileptic drug, using central composite design with response surface methodology (RSM).The present investigation helps to overcome the problem associated with levetiracetam tablets and liquid dosage forms with children and elderly people like bad taste and swallowing difficulties. It also facilitates as an alternative manufacturing process for advanced patented technology like 3D printing process employed in SPRITAM® tablet. Levetiracetam effervescent tablets were prepared by dry granulation (roll compaction) method using water-soluble excipients and optimized by central composite rotatable design (CCRD) using two variables (citric acid and effersoda) at two levels (high and low). Overall, fourteen formulation trials were generated through statistical software Minitab 17.3.0 placing 6 center points, 4 cube points, and 4 axial points. All formulations were subjected to compression using single punch machine. Quality attributes of compressed tablets were evaluated using various compendial and non-compendial tests. RSM was used to observe the responses like effervescent time, hardness, and friability of the prepared tablet batches for different levels of all the variables. Polynomial equations were developed, and model plots (contour plot and 3-dimensional model surface plots) were generated to study the impact of acid-base couple on the responses. Finally, the optimized formulation was selected on the basis of desired effervescent time, hardness, friability, percent drug release, and drug content. From the studied RSM design, it was observed that small changes in the independent variables (citric acid and effersoda) correlate with shifts in the dependent variables, i.e., the desired responses. The study reveals that all the independent variables (citric acid and effersoda) and dependent variables (effervescent time, hardness, and friability) have a good correlation as indicated by good linear regression coefficient of 0.9808, 0.9939, and 0.9892 for effervescent time, hardness, and friability respectively. Levetiracetam effervescent tablets are satisfactorily prepared by dry granulation (roll compaction) approach. All desired critical quality attributes were found to be satisfactory. The applicability of RSM with desirability function in optimizing the levetiracetam formulation has made it possible to identify the impact of various independent variables and explore their effect on required responses.

中文翻译：

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响应面法（RSM）在抗癫痫药左乙拉西坦患者依从性泡腾片制剂的统计优化和药物表征中的应用

本研究的主要目的是使用响应表面方法（RSM）的中心复合设计开发和优化抗癫痫药物左乙拉西坦的泡腾片。本研究有助于克服与​​左乙拉西坦片和液体剂型有关的问题与儿童和老人一样，口味差和吞咽困难。它还有利于替代先进的专利技术制造工艺，例如SPRITAM®平板电脑中采用的3D打印工艺。左乙拉西坦泡腾片采用水溶性赋形剂通过干法制粒（压实法）制备，并通过中央复合旋转设计（CCRD）进行优化，使用两个变量（柠檬酸和effersoda）在两个水平（高和低）下进行。总体，通过统计软件Minitab 17.3.0生成了14个配方试验，其中放置了6个中心点，4个立方体点和4个轴向点。使用单冲床对所有制剂进行压缩。使用各种药典和非药典测试来评估压制片剂的质量属性。对于所有变量的不同水平，使用RSM观察制备的片剂批次的起泡时间，硬度和脆性等响应。开发了多项式方程，并生成了模型图（轮廓图和3维模型表面图）以研究酸碱耦合对响应的影响。最后，根据所需的起泡时间，硬度，易碎性，药物释放百分数和药物含量选择最佳配方。根据研究的RSM设计，据观察，自变量（柠檬酸和艾弗索达）的细微变化与因变量（即所需的响应）的变化相关。研究表明，所有独立变量（柠檬酸和effersoda）和因变量（泡腾时间，硬度和脆性）都具有良好的相关性，泡腾时间，硬度，和易碎性。左乙拉西坦泡腾片通过干法制粒（辊压）法令人满意地制备。发现所有所需的关键质量属性均令人满意。