Suitability of the z-Factor for Dissolution Simulation of Solid Oral Dosage Forms: Potential Pitfalls and Refinements

Abstract

Parameterization of dissolution profiles for subsequent use in in silico modeling and simulation is a crucial element for the success of extrapolating in vitro to in vivo release from solid oral dosage forms. The z-factor dissolution model is an option that can be utilized in commercial software such as GastroPlus™ to simulate the release from solid oral dosage forms. However, several aspects that can confound particle dissolution, such as disintegration and coning, are currently not taken into consideration in this model. To promote a more comprehensive use of the z-factor dissolution model, we discuss the scope of the model in its current modus operandi, highlight problems associated with the current approach and present potential solutions. Taking into account disintegration of dosage forms together with a calculation of the theoretical mass available for dissolution allows for a more realistic z-factor estimate that considers the dissolution process in terms of its two core components, dosage form disintegration and particle dissolution, independently. It is shown that separating these two elements allows for more flexible evaluation and use of the z-factor approach in modeling softwares, as both elements can then be scaled independently to describe the behavior in a range of simulated physiological environments.

Keywords: Disintegration; Dissolution; IR SODF; Modeling and simulation; z-Factor.