Relationship between rheological properties, in vitro release and in vivo equivalency of topical formulations of diclofenac

Publication date: Available online 9 November 2019Source: International Journal of PharmaceuticsAuthor(s): María Pleguezuelos-Villa, Matilde Merino-Sanjuán, Mª Jesús Hernández, Amparo Nácher, Daniel Peris, Irene Hidalgo, Lluís Soler, Marta Sallan, Virginia MerinoAbstractDetermination of bioequivalence remains a challenge in generic topical drug development. To support pharmacokinetic studies, strategies to demonstrate microstructure sameness of the products being compared include in vitro evaluations, such as the comparison of rheological properties, droplet size and in vitro release rates. Nevertheless, defining the appropriate acceptance range to consider equivalence between test and reference formulation is complex.To shed more light into this issue, in vitro release and rheological properties were compared to in vivo bioequivalence data (systemic blood measurements within a clinical trial) after topical application of a single dose. Test and reference formulations of diclofenac diethylamine emulgels were evaluated. While the test formulation met the requirements for equivalence in both the in vivo bioequivalence and in vitro release study, the rheological properties were considered equivalent depending on the criteria used. The 90% confidence interval of the ratios between geometric mean values of both formulations were within the limits of 75-133%, but outside the 90-111% limit under discussion in the scientific community. Altogether these data indicate that diffe...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research