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Contemporary pharmaceutical pipelines are often highly populated with poorly water-soluble drug candidates necessitating novel formulation technologies to provide dosage forms with appropriate biopharmaceutical properties. The configuration of supersaturating drug delivery systems (SDDS) is a promising concept to obtain adequate oral bioavailability. SDDS(More)
Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been(More)
It was the purpose of this study to investigate excipient-mediated precipitation inhibition upon induction of supersaturation of poorly water-soluble drugs in aspirated human intestinal fluids (HIF) representing both the fasted and fed state. Etravirine, ritonavir, loviride, danazol and fenofibrate were selected as model compounds. For comparative purposes,(More)
PURPOSE To explore the effect of the nutritional state on the solubilizing properties of human intestinal fluids (HIF) on a time-after-food administration basis. METHODS HIF were collected in fractions of 30 min from five volunteers in the fasted, fed and fat-enriched fed state. In vitro solubility of five BCS class II drugs (danazol, diazepam,(More)
The purpose of this paper is to collate all recently published solubility data of orally administered drugs in human intestinal fluids (HIF) that were aspirated from the upper small intestine (duodenum and jejunum). The data set comprises in total 102 solubility values in fasted state HIF and 37 solubility values in fed state HIF, covering 59 different(More)
The purpose of this study was to assess the effect of biorelevant apical conditions on intestinal permeability estimation in the Caco-2 system for amprenavir, a poorly water-soluble substrate of the efflux carrier P-glycoprotein (P-gp). To establish biorelevant conditions, human intestinal fluids (HIF) were aspirated from the duodenum and jejunum in fasted(More)
BACKGROUND AND OBJECTIVE Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and(More)
Supersaturating drug delivery systems (SDDS) hold the promise of enabling intestinal absorption for difficult-to-formulate, poorly soluble drug candidates based on a design approach that includes (1) converting the drug into a high energy or rapidly dissolving system which presents a supersaturated solution to the gastrointestinal environment and (2) dosage(More)
In the present study, we successfully downscaled, for the first time, the in situ intestinal perfusion technique with mesenteric blood sampling from rat to mouse. To evaluate the feasibility of this approach, we assessed the apparent permeability (P(app)) of mouse intestine for a set of marker compounds [atenolol, paracellular transport; metoprolol,(More)
PURPOSE The present study investigated the interplay between supersaturation, absorption, precipitation, and excipient-mediated precipitation inhibition by comparing classic precipitation assessment in a non-absorption environment with precipitation/permeation assessment in an absorption environment. Loviride and HPMC-E5 were selected as poorly soluble(More)