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PBPK Modeling in Lieu of Clinical Endpoint Bioequivalence Study for Generic Tazarotene Cream 0.05%

Tazarotene is a novel synthetic retinoid prodrug, with tazarotenic acid being an active metabolite, that can be used for treating psoriasis and acne.​A generic product equivalent to Tazorac Cream, 0.05% has been developed and thoroughly characterized for qualitative (Q1), quantitative (Q2) and physiochemical and structural (Q3) equivalence. In lieu of conducting a clinical endpoint study, a PBPK model was developed. ​The goal was to assess bioequivalence at the site of application and systemic compartments, overcoming the limitations associated with clinical endpoint studies. ​

Simcyp® Simulator multi-phase and multi-layer (MPML) mechanistic dermal absorption (MechDermA) model was used for this investigation.

Bioequivalence of generic tazarotene cream was demonstrated through extensive Q3 characterization coupled with IVPT and systemic absorption/distribution profiles using a validated PBPK model, supporting the FDA approval of a generic product.

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