In vivo predictive mini-scale dissolution for weak bases: Advantages of pH-shift in combination with an absorptive compartment

In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib

“…The implementation of biorelevant media into mGIS could improve the prediction of in vivo dissolution. Also, the implementation of the absorptive phase into in vitro dissolution methodologies, which have been developed as biphase/two-phase dissolution methodology, would contribute the better prediction of in vivo dissolution for poorly water-soluble drugs (Frank et al, 2014;Grundy et al, 1997;Heigoldt et al, 2010;Mudie et al, 2012). The incorporated absorptive phase will apparently remove dissolved drug from aqueous phase, which represents drug absorption from the GI tract and, thus, the biphase/two-phase dissolution methodologies have the potential applicability for improved prediction of in vivo performance for poorly water-soluble drugs.…”

Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics

“…Applying this experimental model, it was possible to predict the in vivo absorption kinetics including bioavailability of various formulations in dogs. Single-phasic dissolution methods, however, were not capable of predicting the in vivo performance adequately [16]. Despite obtaining good results with the miBIdi-pH, the robustness of various experimental model parameters has not been investigated yet.…”

“…1) placed in a laboratory hood. To increase model robustness compared to the previously published dissolution model by Frank et al [16] several improvements were made: (a) the aqueous phase (McIlvaine buffer; volume approximately 50 ml, a factor 10 scaled-down volume from the original USP II apparatus) was filled in mini glass vessels, approximately factor 3.16 scaled-down (cylinder with hemisphere; height: 11.7 cm, diameter: 3.2 cm) and was covered with 30 ml of octanol; (b) the temperature in the vessels was kept at 37°C (water bath); and (c) the dimensions of the new mini paddles resembled an accordingly scale-down miniaturised USP II setup (aqueous paddle: height: 0.6 cm, diameter: 2.1 cm, thickness: 0.11 cm; octanol paddle: height: 0.5 cm, diameter: 1.5 cm, thickness: 0.35 cm). The paddles could be stirred in two directions (co-or counterrotating) and the stirring speed could be adjusted to stirring rates between 25 rpm and 100 rpm.…”

“…These experiments were carried out to test extended release tablets and capsules in a model consisting of 500 ml of aqueous medium and 100 ml of octanol. In the next step a scale-down of this biphasic model was performed accounting for limited API availability at early stage drug product development [16]. High aqueous volumes in combination with relevant dose concentrations leading to non-sink conditions can cause high API consumption.…”

Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules

“…The biphasic dissolution model ideally also enables the evaluation of various formulation factors such as dose strength [22], excipient effects [19,21], drug precipitation [18,23] and particle size [24] on the in vivo performance of poorly soluble drugs. Shi [27].…”