Development and Validation of 'Level A' In Vitro - In Vivo Correlation for Extended Release Tablets of Lamotrigine

Title:Development and Validation of 'Level A' In Vitro - In Vivo Correlation for Extended Release Tablets of Lamotrigine

Volume: 12 Issue: 4

Author(s): Rakesh Jain, Sunil S. Iyer, Praveen Radhakrishnan, Sudershan Kumar, Arshad H. Khuroo and Tausif Monif

Affiliation:

Keywords: Lamotrigine, extended release, dissolution, de-convolution, ivivc, validation, bioequivalence.

Abstract: Background: A quantitative and reliable relationship between in vitro drug release and in vivo absorption is desirable for rational development and optimization of extended release (ER) dosage forms. This article describes the development and validation of an in vitro - in vivo correlation (IVIVC) for ER tablets of Lamotrigine.

Methods: Two prototype extended release tablets of lamotrigine were formulated. Predictive in vitro dissolution method with changing pH of media from acidic to basic condition in Dissolution Apparatus Type II (United State Pharmacopoeia) was developed and the two formulations were evaluated to obtain in vitro data for the development of IVIVC. The in vivo dataset for development of IVIVC (plasma concentration data) was obtained from the two arms of a three-way, crossover study in 12 healthy volunteers after administration of the developed ER tablets. The third arm was a reference formulation for external validation.

Results: An in-house mean plasma concentration data of an immediate release formulation was used to compute the in vivo weighting function. The fraction of drug absorbed was computed using numerical deconvolution and a linear correlation model was developed between fraction absorbed and fraction dissolved from the two formulations. Internal and external validation of the developed model was carried out based on prediction error of pharmacokinetic parameter estimates.

Conclusion: Prediction error was less than 10% for both internal and external validations, demonstrating the validity of the developed model. Hence, the model can be used for comparison and selection of formulations for pivotal bioequivalence study.

Cite this article as:

Jain Rakesh, Iyer S. Sunil, Radhakrishnan Praveen, Kumar Sudershan, Khuroo H. Arshad and Monif Tausif, Development and Validation of 'Level A' In Vitro - In Vivo Correlation for Extended Release Tablets of Lamotrigine, Current Bioactive Compounds 2016; 12 (4) . https://dx.doi.org/10.2174/1573407212666160609130033