Bioequivalence of Topical Products: Elucidating the Thermodynamic and Functional Characteristics of Compositionally Different Topical Formulations

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Abstract The general requirements for generics to be considered are that the product is off-patent, contains an active ingredient in a previously approved medicine and is shown to be bioequivalent to that previously approved medicine. The fundamental forces governing the effects of topical drugs applied to the skin can be summed up in three distinct dimensions. 1. The interaction of the active pharmaceutical ingredient (API) with the excipients (formulation factors, solubility), 2. API with the skin (thermodynamic and pharmacodynamic activity) and 3. Excipient with the skin (penetration enhancement, diffusivity, irritancy). A thoughtful appreciation followed by a thorough understanding and then careful deliberations can help mitigate a number of failure modes that can arise from these three dimensions and result in disapproval of generic drug applications. However, there is an elusive fourth dimension, the psychorheology or the sensory/perceptive judgement of the rheological properties (and other organoleptic properties) that dictates the end user/consumers final acceptance of the product. Through this project we aim to develop meaningful risk mitigating methods and their scientific basis. These will encompass considering product behaviour during various stages of development/manufacturing, all the way to looking at the metamorphosing product as it is being applied to the treatment site on the skin. The development of generic topical products has been hampered by factors such as expensive clinical trials for BE assessment and application costs which get blown out due to the case by case assessment of applications. A burdensome application package is generally needed that wastes valuable resources and time on both sides of the coin. This project will ensure the much needed theoretical and practical framework that can enable a thorough yet efficient assessment of topical generic product applications.