Document Detail

Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: the importance of viscosity.
MedLine Citation:
PMID:  22782559     Owner:  NLM     Status:  MEDLINE    
A negative food effect, i.e. a decrease in bioavailability upon the co-administration of compounds together with food, has been attributed particularly with high solubility/low permeability compounds (BCS class III). Different mechanisms have been proposed including intestinal dilution leading to a lower concentration gradient across the intestinal wall as well as binding of the active pharmaceutical ingredient to food components in the intestine and thereby decreasing the fraction of the dose available for absorption. These mechanisms refer primarily to the compound and not to the dosage form. An increase in viscosity of the dissolution fluid will in particular affect the absorption of BCS type III compounds with preferential absorption in the upper small intestine if the API release is delayed from the dosage form. The present study demonstrated that the increase in viscosity of the dissolution medium, following ingestion of a solid meal, may drastically reduce disintegration and dissolution. For that purpose the viscosity of the standard FDA meal was determined and simulated by solutions of HPMC in buffer. As model formulations, three commercially available tablets containing trospium chloride, a BCS class III m-cholinoreceptor antagonist was used. Trospium chloride drug products have been described to undergo a negative food effect of more than 80% following ingestion with food. The tablets showed prolonged disintegration times and reduced dissolution rates in viscous media, which could be attributed to changes in the liquid penetration rates. The effect was particularly significant for film-coated tablets relative to uncoated dosage forms. The results show the necessity of considering media viscosity when designing in vitro models of drug release for BCS type III drug formulations.
Asma Radwan; Gordon L Amidon; Peter Langguth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-11
Journal Detail:
Title:  Biopharmaceutics & drug disposition     Volume:  33     ISSN:  1099-081X     ISO Abbreviation:  Biopharm Drug Dispos     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-02-25     Revised Date:  2013-05-22    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  England    
Other Details:
Languages:  eng     Pagination:  403-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
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MeSH Terms
Biopharmaceutics / methods*
Chemistry, Pharmaceutical
Computer Simulation
Food-Drug Interactions*
Galactans / chemistry
Gastrointestinal Tract / metabolism*
Mannans / chemistry
Methylcellulose / analogs & derivatives,  chemistry
Models, Biological*
Nortropanes / chemistry*,  pharmacokinetics
Plant Gums / chemistry
Reg. No./Substance:
0/Buffers; 0/Galactans; 0/Mannans; 0/Nortropanes; 0/Plant Gums; 0/Tablets; 1E6682427E/trospium chloride; 8063-82-9/hypromellose; 9000-30-0/guar gum; 9004-67-5/Methylcellulose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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