Document Detail


In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.
MedLine Citation:
PMID:  22815122     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.
Authors:
Yasuhiro Tsume; Peter Langguth; Alfredo Garcia-Arieta; Gordon L Amidon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-21
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:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  7911226     Medline TA:  Biopharm Drug Dispos     Country:  England    
Other Details:
Languages:  eng     Pagination:  366-77     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation:
College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.
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MeSH Terms
Descriptor/Qualifier:
Absorption
Biopharmaceutics / methods*
Computer Simulation
Humans
Hydrogen-Ion Concentration
Ibuprofen* / chemistry,  pharmacokinetics
Intestines / metabolism*
Ketoprofen* / chemistry,  pharmacokinetics
Models, Biological*
Mouth Mucosa / metabolism*
Predictive Value of Tests
Solubility
Tablets
Therapeutic Equivalency
Grant Support
ID/Acronym/Agency:
2R01GM037188/GM/NIGMS NIH HHS; R01 GM037188/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Tablets; 15687-27-1/Ibuprofen; 22071-15-4/Ketoprofen
Comments/Corrections

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


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