生物学的同等性とバイオアベイラビリティのジャーナル

概要

Application of Assumed IVIVC in Product Life Cycle Management: A Case Study of Trimetazidine Dihydrochloride Extended Release Tablet

Varinder Kumar, Lalit Kumar Khurana, Shavej Ahmad and Romi Barat Singh

The purpose of this study was to utilize IVIVC tool in the development of oral controlled release formulation of a BCS class I model drug Trimetazidine dihydrochloride (TMZ). Commercial products of TMZ are taken two to three times a day to achieve therapeutic benefit. Hence, development of once daily tablet was initiated with the development of “Assumed IVIVC”. The assumed IVIVC was developed by obtaining in vivo data of single dose IR formulation (Vastarel® 20 mg) from literature and generating in vitro and in vivo data for Preductal® MR 35 mg modified release tablet (Reference) and TMZ extended release tablet 70 mg (Test) in house. In vitro dissolution ER tablet was conducted by evaluating effect of pH. The in vitro profile as a surrogate to in vivo absorption was generated in 0.1 N HCl medium. The in vivo absorption was calculated using deconvolution approach using the IR data for unit impulse response. A linear model with a time-scaling factor clarified the relationship between the in vitro and the in vivo data. The predictability of the final model was consistent based on internal validation. Average percent prediction errors for pharmacokinetic parameters were within ± 10% and individual values for all formulations were within ± 15%. Same model was used as a target to develop OD tablet using software WinNonlin® IVIVC toolkit™ that would be bioequivalent to 35 mg modified release reference product. The assumed IVIVC was then utilized for “Retrospective IVIVC” development and pharmacokinetic parameters of desired formulations were predicted through the IVIVC model. Predicted results for formulation F4 and F5, projected them as the most suitable for once daily use. In this work, it was demonstrated that the IVIVC can be used in the development of new dosage forms to reduce the number of human studies in product life cycle management.