Effect of cyclodextrin concentration on the oral bioavailability of danazol and cinnarizine in rats

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
René HolmPeter Westh

Abstract

Cyclodextrins (CDs) are frequently used as an excipient to enhance the intestinal drug absorption of compounds with a low aqueous solubility. However, there exists an intricate interplay between opposing effects that determine the optimal dosing criterion. These opposing effects are the benefits of circumventing the dissolution time required to dissolve the non-absorbable drug particles in the intestine versus the disadvantage of decreasing the concentration of the drug available to permeate the intestinal membrane if excessive CD concentrations are used. This study investigated whether there is a potential risk of overdosing CDs in aqueous formulations resulting in suboptimal bioavailability. This was done by measuring the in vivo pharmacokinetics of danazol, which has a high affinity for hydroxypropyl-βCD, and cinnarizine, which has a pH-dependent low to medium affinity. Pharmacokinetic studies of danazol in rats showed a significant longer Tmax and decreased Cmax resulting in decreased bioavailability when the CD concentration was increased. No significant difference was seen for any of the pharmacokinetic parameters for cinnarizine as a function of CD dose. The present study thus demonstrates that surplus CD concentrations ...Continue Reading

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Citations

Mar 13, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Niels Erik OlesenRené Holm
Feb 2, 2019·Current Pharmaceutical Design·Mamunur RashidMuhammad Wahajuddin
Jul 25, 2019·Current Drug Targets·Nidhi NainwalVikas Anand Saharan
Jun 23, 2020·Clinical and Experimental Pharmacology & Physiology·Liliane Barreto da SilvaDarízy Flávia Silva
Jun 9, 2021·Journal of Pharmaceutical Sciences·Jonas Borregaard EriksenMartin Brandl

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