Department of Pharmaceutical Engineering, Catholic University of Daegu, Hayang-Ro 13-13, Hayang-Eup, Gyeongsan 38430, Korea.
Molecules. 2022 Apr 29;27(9):2828. doi: 10.3390/molecules27092828.
Tianeptine tablets are currently marketed to be designed for immediate-release tablets. The tianeptine has a short half-life, making it difficult to design for sustained-release tablets and achieve bioequivalence with the tianeptine immediate-release tablet (Stablon). We established the in vitro-in vivo correlation (IVIVC) of three formulations of tianeptine sustained-release tablets according to their granule size. To evaluate sustained drug release, in vitro tests were performed in pH 1.2 media for 24 h. In vivo pharmacokinetic analysis was performed following oral administration of reference drug and test drug to beagle dogs. The dissolution profile revealed delayed release as the size of the granules increased. The dissolution results were confirmed in pharmacokinetic analysis, showing that the half-life was delayed as granule size increased. The final formulation and reference drug showed an equivalent area under the curve (AUC). Through this, IVIVC was established according to the size of the tianeptine sodium granules, which is the purpose of this study, and was used to predict in vivo pharmacokinetics from the formulation composition. This approach may be useful for determining optimal formulation compositions to achieve the desired pharmacokinetics when developing new formulations.
甲硫苯丙胺片目前市售的设计为速释片。甲硫苯丙胺的半衰期较短，因此难以设计为缓释片，并实现与甲硫苯丙胺速释片（Stablon）的生物等效性。我们根据颗粒大小建立了三种甲硫苯丙胺缓释片的体外-体内相关性（IVIVC）。为了评估药物的持续释放，在 pH 1.2 的介质中进行了 24 小时的体外试验。在口服参比药物和受试药物后，对比格犬进行了体内药代动力学分析。溶解曲线显示随着颗粒尺寸的增加而延迟释放。药代动力学分析结果证实了这一点，表明半衰期随着颗粒尺寸的增加而延迟。最终的配方和参比药物显示出等效的曲线下面积（AUC）。通过这种方式，根据甲硫苯丙胺钠颗粒的大小建立了 IVIVC，这是本研究的目的，并用于从制剂组成预测体内药代动力学。当开发新制剂时，这种方法可能有助于确定最佳的制剂组成以实现所需的药代动力学。
