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Recently, the United States Food and Drug Administration published a series of product-specific guidance for the development of topical drugs, with in vitro options consisting of qualitative sameness (Q1) and quantitative sameness (Q2) assessment of formulations, physiochemical and structural characterization of formulations (Q3), and, potentially, in vitro drug release and permeation tests. In these tests, the topical semisolid product's critical quality attributes (CQAs), such as rheological properties, thermodynamic activity, particle size, globule size, and rate/extent of drug release/permeation, are evaluated to ensure the desired product quality. However, alterations in these CQAs of the drug products may occur under 'in use' conditions because of various metamorphosis events, such as evaporation that leads to supersaturation and crystallization, which may eventually result in specific failure modes of semisolid products. Under 'in use' conditions, a limited amount of formulation is applied to the skin, where physicochemical characteristics of the formulation are substantially altered from primary state to secondary and, eventually, tertiary state on the skin. There is an urgent need to understand the behavior of topical semisolid products under 'in use' conditions. In this review, we attempt to cover a series of metamorphosis events and their impact on CQAs (Q3 attributes), such as viscosity, drug activity, particle size, globule size, and drug release/permeation of topical semisolid products.
Jin et al. (Thu,) studied this question.