In Vitro Tools for Evaluating Novel Dosage Forms of Poorly Soluble, Weakly Basic Drugs: Case Example Ketoconazole. Issue 10 (19th July 2013)

• Record Type: Journal Article
• Authors: Taupitz, Thomas; Dressman, Jennifer B.; Klein, Sandra
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 10(2013:Oct.)
• Page Start: 3645
• Page End: 3652
• Publication Date: 2013-07-19
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23666
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The aim of the present series of experiments was to compare various <italic>in vitro</italic> tools including evaluation of formulations influence on solubility, various dissolution tests, and an updated, miniaturized transfer model to forecast the behavior of novel formulations of the poorly soluble, weakly basic model compound ketoconazole (KETO) after oral administration. A binary complex with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) and a ternary formulation with HP‐β‐CD and Soluplus® were evaluated and their solubility, dissolution, and transfer behavior was compared with that of the pure drug. Binary and ternary formulations could significantly improve (<italic>p</italic> < 0.05) KETO solubility in all test media. Dissolution in media simulating the fasted stomach and the fed small intestine was almost complete for the pure drug and both complex formulations. By contrast, in pH 6.5 FaSSIF, dissolution of the pure drug was less than 10%. Both formulations resulted in significantly higher KETO release (<italic>p</italic> < 0.05) in this test medium (32%/95% release from the binary/ternary formulation). In the transfer experiments, the ternary complex showed the best performance with respect to stabilizing a supersaturated solution and inhibiting precipitation of KETO. Overall, the miniaturized transfer model appeared to be the best single tool for rank‐ordering formulations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3645–3652, 2013</p> </abstract>