Can in vitro/in silico tools improve colonic concentration estimations for oral extended-release formulations? A case study with upadacitinib.

Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution.

Digitalizing the TIM-1 Model using Computational Approaches-Part One: TIM-1 Data Explorer.

The TIM-1 gastrointestinal model is one of the most advanced in vitro systems currently available for biorelevant dissolution testing. This technology, the initial version of which was developed nearly 30 years ago and has been subject to a number of significant updates over this period, simulates the dynamic environment of the human gastrointestinal tract, including pH, transfer times, secretion of bile, enzymes, and electrolytes. In the pharmaceutical industry, the TIM-1 system is used to support drug product design and provide a biopredictive assessment of drug product performance.

Digitalizing the TIM-1 Model Using Computational Approaches─Part Two: Digital TIM-1 Model in GastroPlus.

A TIM-1 model is an gastrointestinal (GI) simulator considering crucial physiological parameters that will affect the drug release process. The outcome of these experiments can indicate the critical bioavailability attributes (CBAs) that will impact the fraction absorbed . The model is widely used in the nonclinical stage of drug product development to assess the bioaccessible fraction of drugs for numerous candidate formulations.

Investigating the relationship between periodontitis and specific memory processes in the search for cognitive markers of Alzheimer's disease risk.

The spontaneous retrieval deficit (SRD) hypothesis argues that individuals in the preclinical stages of Alzheimer's disease (AD) are particularly impaired in spontaneous retrieval, which manifests in reduced mind-wandering. Our main purpose was to provide novel evidence to support the SRD hypothesis by investigating, for the first time, the relationship between mind-wandering and periodontitis, the latter being the risk factor for AD. The second objective was to address the lack of deeper understanding of the relationship between oral health and specific cognitive abilities by investigating whether periodontitis would be primarily associated with memory.