Validated correlation of mass loss and drug release in vitro and in healthy subjects for sugared and sugar-free cetylpyridinium chloride (CPC) and benzocaine (1.4 mg/10 mg) lozenges supports in vitro mass loss and corresponding drug release as a surrogate for local bioequivalence

• Published in: Journal of drug delivery science and technology Vol. 77; p. 103822
• Main Authors: Cardot, Jean-Michel, Savania, Nina, Targett, Darren, Freeman, Ben, Gray, Helen, Stahl, Tessa, Kästner, Uta, Kulasekaran, Anuradha
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2022
• Subjects: Benzocaine; Biopredictive model; Biowaivers; Cetylpyridinium chloride; In vitro–in vivo correlation; Lozenges; Oropharyngeal cavity; BCa; CRO; DE; Biopredictive model; IVIVC; Cetylpyridinium chloride; CI; Lozenges; Biowaivers; f2; AUC; Benzocaine; ANOVA; EMA; Oropharyngeal cavity; IRF; In vitro–in vivo correlation
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2022.103822

A clinical study was performed to determine the in vivo mass loss of both lozenges in 16 healthy volunteers. In vitro, mass loss over time was measured for both formulations and correlated to the release of CPC and benzocaine. In vivo, the oral mass loss profiles of both lozenges were similar, with a mean difference between the two curves, up to the first point greater than 85% of 3.2%, and a f2 similarity factor of 69%. In vitro, the mass loss of both lozenges was similar and a strong correlation between mass loss and release of CPC and benzocaine was observed, indicating that the active ingredients were homogeneously dispersed within the lozenges. Based on the results, it was possible to establish a link between the in vitro and in vivo drug release and mass losses using an in vitro–in vivo correlation (IVIVC). In vivo release profiles of benzocaine and CPC were calculated and found to be similar for the sugar-free and sugared lozenges; more than 85% of the active ingredients were released in 186 and 209 s, respectively. These results suggest that in vitro mass loss and corresponding drug release is an adequate surrogate for bioequivalence studies, waiving their need for lozenges with excipient changes, and that the clinical risk–benefit profile of sugar-free CPC/benzocaine (1.4 mg/10 mg) lozenges is unlikely to differ from sugared lozenges. [Display omitted]