Conventional vs Mechanistic IVIVC: A Comparative Study in Establishing Dissolution Safe Space for Extended Release Formulations.

The use of in vitro-in vivo correlation (IVIVC) for extended release oral dosage forms is an important technique that can avoid potential clinical studies. IVIVC has been a topic of discussion over the past two decades since the inception of USFDA guidance. It has been routinely used for biowaivers, establishment of dissolution safe space and clinically relevant dissolution specifications, for supporting site transfers, scale-up and post approval changes.

Physiologically based pharmacokinetic modelling to predict drug-drug interactions for encorafenib. Part I. Model building, validation, and prospective predictions with enzyme inhibitors, inducers, and transporter inhibitors.

Encorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses potential for enzyme-transporter related interactions. Clinically, its drug-drug interactions (DDIs) with CYP3A4 inhibitors (posaconazole, diltiazem) were reported and hence there is a necessity to study DDIs with multiple enzyme inhibitors, inducers, and P-gp inhibitors.

Physiologically based pharmacokinetic modeling (PBPK) to predict drug-drug interactions for encorafenib. Part II. Prospective predictions in hepatic and renal impaired populations with clinical inhibitors and inducers.

Encorafenib, a potent BRAF kinase inhibitor gets significantly metabolised by CYP3A4 (83%) and CYP2C19 (16%) and is a substrate for P-glycoprotein (P-gp). Due to significant metabolism by CYP3A4, encorafenib exposure can increase in hepatic and renal impairment and may lead to altered magnitude of drug-drug interactions (DDI). Hence, it is necessary to assess the exposures & DDI's in impaired population.