Document Detail

In vivo performance of an oral MR matrix tablet formulation in the beagle dog in the fed and fasted state: assessment of mechanical weakness.
MedLine Citation:
PMID:  17917709     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To evaluate the behaviour of an oral matrix modified release formulation in the canine gastrointestinal tract, and establish if a mechanical weakness previously observed in clinical studies would have been identified in the dog model. MATERIALS AND METHODS: In vitro release profiles were obtained for two modified release matrix tablets containing UK-294,315, designed to release over either 6 (formulation A) or 18 (formulation B) hours. Tablets were labelled with (153)samarium and in vivo pharmacoscintigraphy studies were performed in four beagle dogs in the fasted state for both formulations, and following ingestion of an FDA high fat meal for formulation B. RESULTS: The matrix tablet formulations displayed significantly different in vitro release profiles (F (2) < 50), with time to 80% release for formulation A and B of 406 and 987 min respectively. Complete in vivo disintegration occurred at 339 +/- 181 and 229 +/- 171 for formulation A and B respectively in the fasted state, and at 207 +/- 154 min for formulation B in the fed state, in disagreement with in vitro release. CONCLUSION: The fed/fasted dog model would have predicted a lack of physical robustness in the matrix tablet formulation B, however it would not have predicted the clear fed/fasted effects on performance observed previously in man.
Fiona McInnes; Nicola Clear; Michael Humphrey; Howard N E Stevens
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-05
Journal Detail:
Title:  Pharmaceutical research     Volume:  25     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-10     Completed Date:  2008-06-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1075-84     Citation Subset:  IM    
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
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MeSH Terms
Area Under Curve
Azepines / administration & dosage,  chemistry
Chemistry, Pharmaceutical
Delayed-Action Preparations / administration & dosage,  chemistry*
Drug Compounding
Fasting / metabolism*
Gastrointestinal Transit
Hardness Tests
Injections, Intravenous
Pharmaceutical Solutions
Quinolines / administration & dosage,  chemistry
Radioisotopes / pharmacokinetics
Samarium / pharmacokinetics
Reg. No./Substance:
0/4-amino-5-(4-fluorophenyl)-6,7-dimethoxy-2-(4-(morpholinocarbonyl)--perhydro-1,4-diazepin-1-yl)quinoline; 0/Azepines; 0/Delayed-Action Preparations; 0/Pharmaceutical Solutions; 0/Quinolines; 0/Radioisotopes; 0/Tablets; 7440-19-9/Samarium

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

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