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European Journal of Pharmaceutical Sciences
Article . 2018 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Mechanistic study on hydrodynamics in the mini-scale biphasic dissolution model and its influence on in vitro dissolution and partitioning

Authors: Kathrin, Locher; Jens M, Borghardt; Herbert, Wachtel; Kerstin J, Schaefer; Karl G, Wagner;

Mechanistic study on hydrodynamics in the mini-scale biphasic dissolution model and its influence on in vitro dissolution and partitioning

Abstract

Biphasic dissolution models were proposed to provide good predictive power for in vivo absorption kinetics. However, up to date the impact of hydrodynamics in mini-scale models are not well understood. Consequently, the aim of this work was to investigate different setups of a previously published mini-scale biphasic dissolution model (miBIdi-pH-II) to better understand the relevance of hydrodynamics for evaluating kinetic parameters and to simultaneously increase the robustness of the experimental model. As a first step, the hydrodynamics within the aqueous phase were characterized by in silico simulations of the flow patterns. Different settings, such as higher rotation speeds of the paddles, the implementation of a second propeller into the aqueous phase, and different shapes of aqueous stirrers were investigated. Second, to evaluate the results of the in silico simulations, in vitro experiments with glitter were carried out. Last, the same settings were applied in the miBIdi-pH-II using dipyridamole (DPD) as model compound to estimate kinetic parameters by applying a compartment-based modelling approach. Both in vitro experiments with glitter or DPD demonstrated the adequateness of the previous in silico hydrodynamic simulations. The use of higher rotation speeds and a second aqueous propeller resulted in more homogeneous mixing of the aqueous phase. This resulted in faster distribution of dissolved active pharmaceutical ingredient (API) into the octanol phase. A kinetic model was successfully applied to quantify the influence of hydrodynamics on the partitioning rate of the API into the octanol phase. In conclusion, the combination of in silico and in vitro methods was demonstrated to be powerful for investigating the flow patterns within the miBIdi-pH-II. A comprehensive understanding of the hydrodynamics and the respective influence on the dissolution and apparent partitioning into the octanol phase in the biphasic dissolution model was obtained and completed by using a compartmental kinetic model. This model allowed successful quantification of how the hydrodynamics influence the partitioning of API into the octanol phase.

Keywords

Drug Liberation, Hydrodynamics, Water, Dipyridamole, 1-Octanol, Models, Theoretical

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Top 10%
Average
Average
gold