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Open AccessArticle

On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development

1
Pion Inc. (UK) Ltd., Forest Row, East Sussex RH18 5DW, UK
2
Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, GR 157 84 Zografou, Greece
3
School of Life Sciences, Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Hofackerstrasse 30, 4132 Muttenz, Switzerland
4
Department of Pharmaceutical Sciences, University of Basel, CH 4056 Basel, Switzerland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 272; https://doi.org/10.3390/pharmaceutics12030272
Received: 18 February 2020 / Revised: 8 March 2020 / Accepted: 11 March 2020 / Published: 16 March 2020
A small-scale biphasic dissolution setup and a small-scale dissolution-permeation (D-P) setup were evaluated for their usefulness in simulating the luminal precipitation of three lipophilic weak bases—dipyridamole, ketoconazole and itraconazole. The transition from the gastric to intestinal environment was incorporated into both experimental procedures. Emulsification during the biphasic dissolution experiments had a minimal impact on the data, when appropriate risk mitigation steps were incorporated. Precipitation parameters estimated from the in vitro data were inputted into the Simcyp® physiologically based pharmacokinetic (PBPK) modelling software and simulated human plasma profiles were compared with previously published pharmacokinetic data. Average Cmax and AUC values estimated using experimentally derived precipitation parameters from the biphasic experiments deviated from corresponding published actual values less than values estimated using the default simulator parameters for precipitation. The slow rate of transport through the biomimetic membrane in the D-P setup limited its usefulness in forecasting the rates of in vivo precipitation used in the modelling of average plasma profiles. View Full-Text
Keywords: precipitation; supersaturation; biorelevant; in vitro techniques; PBPK modelling; biphasic dissolution; dissolution-permeation precipitation; supersaturation; biorelevant; in vitro techniques; PBPK modelling; biphasic dissolution; dissolution-permeation
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MDPI and ACS Style

O’Dwyer, P.J.; Imanidis, G.; Box, K.J.; Reppas, C. On the Usefulness of Two Small-Scale In Vitro Setups in the Evaluation of Luminal Precipitation of Lipophilic Weak Bases in Early Formulation Development. Pharmaceutics 2020, 12, 272.

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