Two-step in vitro-in vivo correlations: Deconvolution and convolution methods, which one gives the best predictability? Comparison with one-step approach

Abstract

Finding predictive dissolution tests and valid IVIVCs are essential activities in generic industry, as they can be used as substitutes of human bioequivalence studies. IVIVCs can be developed by two different strategies: a one-step approach or a two-step approach. The objectives of this work were to compare different deconvolution and convolution methods used in the development of two-step level A IVIVCs and to study if the relationship between the in vitro dissolution rate and the in vivo dissolution rate should guide the decision between using a two-step approach or a one-step approach during the development of a new IVIVC. When the in vitro and the in vivo dissolution rates had a linear relationship, valid and biopredictive two-step IVIVCs were obtained, although there was not a combination of deconvolution and convolution methods that could be named as the best one, as long as all the prediction errors for any combination were within the limits. It was not possible to obtain a valid two-step IVIVC when the relationship between dissolution rates was non-linear, but the one-step approach was able to overcome this fact and it gave valid IVIVCs regardless of whether the relationship between dissolution rates was linear or non-linear.

Keywords: BCS; Bioequivalence; IVIVC; One-step; Predictive in vivo-dissolution; Two-step.