Linked Life Data

14727847

Source:http://linkedlifedata.com/resource/pubmed/id/14727847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-19
pubmed:abstractText
This study evaluated the effects of batch size on the in vitro dissolution and the in vivo bioavailability of immediate release formulations of propranolol hydrochloride and metoprolol tartrate. The formulations were manufactured as small and large batches (6 kg and 60 kg for propranolol; 14 kg and 66 kg for metoprolol), and dissolution was performed using USP Apparatus I at 100 rpm and pH 1.2. Two panels of 14 subjects each were randomly assigned to receive the small and large batches of either propranolol or metoprolol in an open, randomized single-dose study. Blood samples were collected over a 24-hour (propranolol) or 18-hour (metoprolol) period and analyzed by validated methods. As determined by the f2 metric (similarity factor), the dissolution of the small and large batches of propranolol and metoprolol was similar. The mean Cmax and AUC(inf) for the small batch of propranolol were 79.0 microg/L and 536 microg/L/hr, and for the large batch they were 83.5 microg/L and 575 microg/L/hr. Cmax and AUC(inf) for the small batch of metoprolol were found to be 95.5 microg/L and 507 microg/L/hr and for the large batch, 95.1 microg/L and 495 microg/L/hr. The 90% confidence intervals for the small and large batches were within the 80% to 120% range for lnCmax, and lnAUC(inf) for both the propranolol and metoprolol formulations. These results suggest that the scale-up process does not significantly affect the bioavailability of highly soluble, highly permeable drugs and in vitro dissolution tests may be useful in predicting in vivo behavior.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1530-9932
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E14
pubmed:dateRevised
2010-11-9
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Scale-up effects on dissolution and bioavailability of propranolol hydrochloride and metoprolol tartrate tablet formulations.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA. neddingt@rx.umaryland.edu
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial