Development and validation of a Level A in-vitro in-vivo correlation for tofacitinib modified-release tablets using extrudable core system osmotic delivery technology.

PURPOSE: To determine if a validated Level A in-vitro in-vivo correlation (IVIVC) could be achieved with the extrudable core system (ECS) osmotic tablet platform. Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis.

METHODS

Fast-, medium-, and slow-release modified-release formulations of 11 mg tofacitinib ECS tablets, and one formulation of 22 mg tofacitinib ECS tablet, were manufactured. In vitro dissolution of the tofacitinib ECS tablets was performed using USP Apparatus 2 (paddles) and in vivo pharmacokinetic (PK) data were obtained from a Phase 1 study in healthy volunteers. A 5 mg immediate-release formulation tablet was included to support deconvolution of the tofacitinib ECS PK tablet data to obtain the in vivo absorption profiles. A linear, piecewise correlation and a simple linear correlation were used to build and validate two IVIVC models.

RESULTS

The prediction errors (PEs) for the linear, piecewise correlation met the Food and Drug Administration's criteria for establishing a Level A IVIVC, with a maximum absolute individual internal PE of 4.6%, a maximum absolute average internal PE of 3.9%, and a maximum absolute external PE of 8.4% obtained.

CONCLUSIONS

This study demonstrates that the tofacitinib ECS osmotic tablet platform can achieve a Level A IVIVC, similar to other osmotic delivery systems.