Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles.

A biorelevant in vitro release/permeation system for oral transmucosal dosage forms.

This research describes the development and validation of a biorelevant in vitro release/permeation system to predict the in vivo performance of oral transmucosal dosage forms. The system is a biorelevant bidirectional transmucosal apparatus which allows better simulation of oral cavity physiological variables in comparison to compendial dissolution apparatuses and therefore may be a better predictor of in vivo behavior. The feasibility of the bidirectional apparatus was studied using smokeless tobacco (snus) as a model oral transmucosal product.