Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, MD, USA.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1300-9. doi: 10.1016/j.ejpb.2013.06.006. Epub 2013 Jun 22.
The aim of present research was to design and evaluate orally disintegrating tablet (ODT) of novel lamotrigine-cyclamate salt. Box-Behnken response surface methodology was selected to design the optimized formulation. The independent factors selected were tablet hardness (X1), disintegrant (X2) and lubricant (X3) levels, and responses chosen were disintegration time (DT, Y1), friability (Y2), T50 (Y3), and T90 (Y4). The tablets were also characterized for drug uniformity by near infrared chemical imaging (NIR-CI) and taste masking evaluation by electronic tongue. All the selected independent variables were statistically (p<0.05) effect the Y1 while Y2, Y3, and Y4 affected only by X2. The optimized ODT was found to meet the regulatory requirement of DT and friability specification. The NIR-CI images indicated uniform distribution of active and inactive ingredients within the tablets. The electronic tongue results were analyzed by principle component analysis (PCA). It indicated that novel salt of lamotrigine and its ODT formulation have a taste similar to cyclamic acid which is indicated by close proximity on PCA score plot, lower Euclidean distance, and high discrimination index values. Furthermore, these parameters were very close to ODT placebo formulation. On the other hand, lamotrigine, its ODT, and placebo formulation were far from each other. In summary, lamotrigine salt provides another avenue for pediatric friendly formulation for children and will enhance patience compliance.
本研究旨在设计和评估新型拉莫三嗪-环氨酸盐的口腔崩解片（ODT）。选用 Box-Behnken 响应面法设计优化配方。选择的独立因素为片剂硬度（X1）、崩解剂（X2）和润滑剂（X3）水平，选择的响应为崩解时间（DT，Y1）、脆碎度（Y2）、T50（Y3）和 T90（Y4）。还通过近红外化学成像（NIR-CI）对片剂进行药物均匀性特征分析，并通过电子舌进行掩味评价。所有选定的独立变量均对 Y1 具有统计学意义（p<0.05），而 Y2、Y3 和 Y4 仅受 X2 影响。优化的 ODT 被发现符合 DT 和脆碎度规格的监管要求。NIR-CI 图像表明活性和非活性成分在片剂内均匀分布。通过主成分分析（PCA）分析电子舌结果。结果表明，拉莫三嗪新型盐及其 ODT 制剂的味道与环己氨酸相似，这一点在 PCA 得分图上接近、欧几里得距离低和高判别指数值上均有所体现。此外，这些参数与 ODT 安慰剂制剂非常接近。另一方面，拉莫三嗪、其 ODT 和安慰剂制剂彼此相距甚远。总之，拉莫三嗪盐为儿童提供了另一种适合儿童的友好型制剂途径，将提高患者的顺应性。
