Application of a novel PhysioCell apparatus for biopredictive dissolution tests of oral immediate release formulations – A case study workflow for in vitro-in vivo predictions

• Published in: International journal of pharmaceutics 2023-06, Vol.641, p.123061-123061, Article 123061
• Main Authors: Romański, Michał, Staniszewska, Marcela, Paszkowska, Jadwiga, Dobosz, Justyna, Romanova, Svitlana, Pieczuro, Jarosław, Kątny, Michał, Roznerska, Dagmara, Szczepański, Janusz, Schraube, Michał, Renn-Hojan, Monika, Puk, Ewa, Hrem, Oksana, Garbacz, Grzegorz, Danielak, Dorota
• Format: Article
• Language: English
• Subjects: Administration; Biological; Chemistry; Drug liberation; In vitro techniques; Oral; Pharmaceutical/methods; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.123061

[Display omitted] •First application of PhysioCell in the model-informed generic product’s development.•Simulated gastric pressure waves differently impacted the tested formulations.•Tablet disintegration found as a drug dissolution rate-limiting factor.•Stress-related disintegration enhancement involved in the mechanistic modeling.•In vitro-in vivo predictions agreed with the reported drug concentrations in plasma. Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tablets: the originator (Brintellix) and generic product candidates (VORTIO). The dissolved drug was monitored in the gastric (StressCell) and intestinal (Collection Vessel) compartments that contained biorelevant media. Simulated intermittent gastric stress at 15 min and “housekeeping wave” at 30 min increased the dissolution of Brintellix formulations only. A mechanistic model that best described the observations involved the first-order tablet disintegration with a stress-induced enhancement for Brintellix, dissolution of solid particles in the StressCell, and drug transfer to the Collection Vessel. Then, a semi-mechanistic pharmacokinetic model with dissolution parameters as inputs simulated vortioxetine plasma concentrations in healthy volunteers after single and multiple dosing of Brintellix. Despite different dissolution characteristics, VORTIO provided similar concentration profiles to the originator. In conclusion, PhysioCell dissolution tests, combined with semi-mechanistic IVIVP, can be successfully used to develop IR dosage forms exhibiting gastric stress-related effects.