LAUSR

Pharmacokinetic evaluations and modeling in order to correlate in vitro drug dissolution kinetics with their in vivo release and absorption kinetics, estimated from the deconvolution of their pharmacokinetic data, is known as IVIVC. IVIVC is a main tool in the development of new drug formulations, and is required by regulators in the case of extended-release drugs, following wellestablished procedures that have subsequently been tried in applications for immediate-release medicinal products (Emami, 2010; Cardot and Davit, 2012). Additionally, successful IVIVCs allow subsequent waivers of in vivo studies for bioequivalence (Karalis et al., 2010). In most cases, applications of such correlations for immediate release lipophilic drugs encounter difficulties due to slow and incomplete dissolution from dosage forms, extensive metabolism, distribution in deep compartments, and enterohepatic circulation (Chrenova et al., 2010). Recently, an alternative IVIVCmethod for such drugs has been proposed: the correlation between the dissolution kinetics of parent drugs in vitro and the plasma kinetics of their metabolites (Mircioiu et al., 2019), mainly due to the fact that metabolites have a simpler pharmacokinetic model (Marchidanu et al., 2013). On the other hand, the performance of IVIC is dependent on the results of in vitro dissolution methods. It is necessary to model the release kinetics and establish the most biorelevant method (Cardot and Davit, 2012; Preda et al., 2012; Paolino et al., 2019). The use of metabolites PK in the evaluation of bioequivalence is also a challenge. There are critical situations that cannot be solved without an evaluation of the metabolites if: 1) the parent drug levels in plasma are too low to allow accurate analytical measurements, 2) the parent drug is unstable in the biological matrix, 3) the parent drug is an inactive prodrug, 4) the formation of the metabolite occurs rapidly, or 5) the metabolite significantly contributes to the overall net activity. In the frame of this research topic, contributions have been received concerning:—Development of biorelevant in vitro dissolution tests