Automated small-scale in vitro transfer model as screening tool for the prediction of in vivo-dissolution and precipitation of poorly solubles

Increasing the Robustness of Biopharmaceutical Precipitation Assays – Part II: Recommendations on the use of FaSSIF

“…al. 7,26 While it was not possible to fully explain this behavior, the precipitation of different polymorphic forms and the transfer being faster than the precipitation rates were discussed as potential reasons in these studies. With respect to the findings of the current study, a significant impact of the colloidal structures in FaSSIF on the precipitation kinetics of ketoconazole may also be reasonable.…”

“…For the solubility experiments, FaSSIF-V1 was prepared with FaSSIF/FeSSIF/FaSSGF-powder (SIF powder) according to the instructions from biorelevant.com. In case of the transfer experiments, the phosphate buffer concentration was doubled to prevent a decrease in pH during the transfer, as suggested by Jede et al 7 Further transfer experiments were performed with FaSSIF which was prepared with higher SIF powder concentrations (150 and 200%) to account for the dilution during the transfer with simulated gastric media. For FaSSIF preparation, different SIF powder batches were used (see Table 1) and for some experiments, stressed SIF powder samples were used for media preparation (see section 2.3).…”

“…For the gastric compartment in the transfer experiments, simulated gastric fluid sine pepsin (SGF sp ) was applied. The pH was adjusted to 2.0 to keep the pH in the acceptor compartment at a physiological level, as formerly proposed by Jede et al 7…”

“…To mimic gastric emptying in fasted humans as closely as possible first order kinetics with a half-life of 5 min were selected. 7 The transfer rate of the peristaltic pump was controlled by a self-programmed software (Python Software Foundation, version 3.7 8 ). The 25 ml donor solution were transferred within 28 min.…”

Improved Prediction of in Vivo Supersaturation and Precipitation of Poorly Soluble Weakly Basic Drugs Using a Biorelevant Bicarbonate Buffer in a Gastrointestinal Transfer Model

“…Small-Scale Experiments with FaSSIF phosphate . A previously described small-scale in vitro transfer model 15,28 was applied to test the supersaturation and precipitation behavior of the weakly basic model compounds in FaSSIF phosphate (Figure 2). This model allows the simulation of the transfer of dissolved or dispersed API from a gastric into a small intestinal compartment.…”