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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics

Background:

• Tianeptine immediate-release tablets (Stablon®) have a short half-life, complicating sustained-release formulation development.
• Achieving bioequivalence for sustained-release tianeptine formulations presents significant challenges.

Purpose of the Study:

• To establish an in vitro-in vivo correlation (IVIVC) for tianeptine sustained-release tablets.
• To investigate the impact of tianeptine sodium granule size on drug release and pharmacokinetic profiles.
• To enable prediction of in vivo pharmacokinetics from formulation composition for optimized drug delivery.

Main Methods:

• In vitro dissolution testing of three tianeptine sustained-release tablet formulations in pH 1.2 media for 24 hours.
• In vivo pharmacokinetic analysis in beagle dogs following oral administration of reference and test drug formulations.
• Correlation of in vitro dissolution data with in vivo pharmacokinetic parameters, including half-life and area under the curve (AUC).

Main Results:

• Increased granule size of tianeptine sodium resulted in delayed in vitro drug release.
• Pharmacokinetic analysis confirmed delayed drug half-life with increasing granule size.
• The final tianeptine sustained-release formulation demonstrated an equivalent area under the curve (AUC) compared to the reference drug.

Conclusions:

• An IVIVC was successfully established for tianeptine sodium sustained-release tablets, directly linked to tianeptine sodium granule size.
• This IVIVC provides a predictive model for in vivo pharmacokinetics based on formulation characteristics.
• The findings support a formulation development approach to achieve desired pharmacokinetic profiles for new tianeptine formulations.