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The impact of food components on the intrinsic dissolution rate of ketoconazole

Ghazal, HS and Dyas, AM and Ford, JL and Hutcheon, GA (2015) The impact of food components on the intrinsic dissolution rate of ketoconazole. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 41 (10). pp. 1647-1654. ISSN 0363-9045

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Abstract

To accurately predict the in vivo performance of drugs from an in vitro dissolution test, the dissolution conditions used are supposed to be similar to those present in the gastrointestinal milieu. Post-prandial gastric fluid contains partially digested food mixtures consisting of fat, protein and carbohydrate. Despite this, the compendia dissolution medium recommended to simulate the gastric fluid is still composed of a simple solution of hydrochloric acid and sodium chloride with or without the addition of pepsin. Therefore, in this investigation, biorelevant dissolution media were developed to evaluate the impact of food constituents; milk with different fat contents, egg albumin, gelatin, casein, gluten, carbohydrates and amino acids on the intrinsic dissolution behavior of ketoconazole. Most of the food additives that were evaluated enhanced the apparent solubility of the drug but to different extents. The greatest enhancement in dissolution was observed in media containing either neutral amino acids or media based on milk mixtures. The formation of complexes between the drug and the additives most likely accounted for the solubilizing effect and in milk-containing media, the effect was attributed to the whole complex structure of milk rather than simply its fat content. These results highlight the potential effect of the type of ingested meal on drug dissolution and subsequent bioavailability.

Item Type: Article
Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Drug Development and Industrial Pharmacy on 1 January 2015, available online: http://dx.doi.org/10.3109/03639045.2014.983114
Uncontrolled Keywords: 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: TAYLOR & FRANCIS LTD
Related URLs:
Date Deposited: 18 Jan 2016 12:30
Last Modified: 06 Sep 2017 13:50
DOI or Identification number: 10.3109/03639045.2014.983114
URI: http://researchonline.ljmu.ac.uk/id/eprint/2650

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