More Than a Gut Feeling─A Combination of Physiologically Driven Dissolution and Pharmacokinetic Modeling as a Tool for Understanding Human Gastric Motility.

studies of formulation performance with and/or simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by combining biopredictive dissolution tests in an innovative apparatus with mechanistic physiology-based pharmacokinetic modeling. The methodology was based on the pharmacokinetic data from a large ( = 118) cohort of healthy volunteers who ingested a capsule containing a highly soluble and rapidly absorbed drug under fasted conditions.

Absence of SARS-CoV-2 in wildlife of northeastern Minnesota and Isle Royale National Park.

Aims: We investigated the presence of SARS-CoV-2 in free-ranging wildlife populations in Northeastern Minnesota on the Grand Portage Indian Reservation and Isle Royale National Park.

Methods And Results: One hundred twenty nasal samples were collected from white-tailed deer, moose, grey wolves and black bears monitored for conservation efforts during 2022-2023. Samples were tested for viral RNA by RT-qPCR using the CDC N1/N2 primer set.

Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug.

Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. In this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast.

Simulation of the Fasted Gastric Conditions and Their Variability to Elucidate Contrasting Properties of the Marketed Dabigatran Etexilate Pellet-Filled Capsules and Loose Pellets.

Variability of the gastrointestinal tract is rarely reflected in test protocols but often turns out to be crucial for the oral dosage form performance. In this study, we present a generation method of dissolution profiles accounting for the variability of fasted gastric conditions. The workflow featured 20 biopredictive tests within the physiological variability.

An extension of biorelevant fed-state dissolution tests to clinical pharmacokinetics - A study on gastrointestinal factors influencing rivaroxaban exposure and efficacy in atrial fibrillation patients.

A direct oral anticoagulant rivaroxaban fails to prevent stroke and systemic embolism in one-to-several percent of patients with nonvalvular atrial fibrillation (NVAF), but the reasons are unknown. The study used semi-mechanistic in vitro-in vivo prediction (IVIVP) modeling to explore the reasons for ineffective thrombosis prevention in NVAF patients. Steady-state drug concentrations in plasma were measured at 0 h (C), 3 h (C), and 12 h post-dosing in thirty-four patients treated with 20 mg rivaroxaban daily.