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. 2022 Apr 29;27(9):2828.
doi: 10.3390/molecules27092828.

In Vitro-In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets

Ye-Ji Lee  1 , Joo-Eun Kim  1
Affiliations

In Vitro-In Vivo Correlation of Tianeptine Sodium Sustained-Release Dual-Layer Tablets

Ye-Ji Lee et al. Molecules. .

Abstract

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.

Keywords: daily administration; in vitro dissolution study; in vitro–in vivo correlation; in vivo pharmacokinetics study; sustained-release tablet; tianeptine sodium.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Morphology of (A) F1, (B) F2, (C) F3 particle observed through stereo binocular microscopy/(D) F1, (E) F2, (F) F3 particle observed through scanning electron microscope (scale bar = 1 mm).
Figure 2
Figure 2
Dissolution profile of tianeptine sodium (TS) from reference drug and (A) F1, (B) F2, and (C) F3 test drug at pH 1.2. Each value represents the mean ± SD (n = 6). The reference drug, Stablon® tablets (tianeptine sodium immediate-release tablet/taken three times per day); test drug, TSR tablets (tianeptine sodium sustained-release tablet/taken once per day).
Figure 3
Figure 3
Plasma concentration-time profiles of (A) F1 (B) F2, and (C) F3 of TSR tablets (37.5 mg/head [QD]) and Stablon® tablets (12.5 mg/head [TID]). Each value represents the mean ± SD (n = 6). Stablon® tablets, tianeptine sodium immediate-release tablets taken three times per day; TSR tablets, tianeptine sodium sustained-release tablets taken once per day.
Figure 4
Figure 4
Manufacturing process of the TSR Tablet.
See this image and copyright information in PMC

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