In vivo dissolution of poorly water-soluble drugs:Proof of concept based on fluorescence bioimaging

In vitro-in vivo correlation(IVIVC)of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients.Nevertheless,in vivo dissolution profles have never been accurately portrayed.The current practice of IVIVC has to resort to in vivo absorption fractions(Fa).In this proof-of-concept study,in vivo dissolution of a model poorly watersoluble drug fenofbrate(FNB)was investigated by fuorescence bioimaging.FNB crystals were frst labeled by near-infrared fuorophores with aggregation-caused quenching properties.The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media,enabling accurate monitoring of residual drug crystals.The linearity established between fuorescence and crystal concentration justifed reliable quantifcation of FNB crystals.In vitro dissolution was frst measured following pharmacopoeia monograph protocols with well-documented IVIVC.The synchronicity between fuorescence and in vitro dissolution of FNB supported using fuorescence as a measure for determination of dissolution.In vitro dissolution correlated well with in vivo dissolution,acquired by either live or ex vivo imaging.The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with Faobtained from pharmacokinetic data.

Oral product input to the GI tract： GIS an oral product performance technology

The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an in vivo predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ＇age of the drug＇, i.e., the ＇magic bullet＇, the 21st century must become the ＇age of the guided missile＇, i.e., the delivery system, including the form of the active pharmaceutical ingredient （API） （＇drug＇）. The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release （IR） dosage forms cannot be optimal for all drugs or likely even any drugs （APIs）. Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs？ It is usually through ＇trial and error＇, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted in vivo drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator （GIS）, which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the super- saturation and the precipitation of pharmaceutical pro- ducts, which is useful information to predict in vivo dissolution of pharmaceutical products. This system canprovide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.