Mechanism of Optical Isomerization Of(s)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxopyrrolo[3,2,1-jk] [L,4]-Benzodiazepine-3-y1]-1h-indole-2-carboxamide (FK480) in Soft Capsules Containing Polyethylene Glycol 400 and Glycerol
Pharmaceutical research(1994)
Abstract
FK480 is a new synthetic non-peptide antagonist of cholecystokinin (CCK)-A receptors. The dosage form of FK480 is a soft capsule containing a solution of FK480 in a mixture of polyethylene glycol 400 (PEG 400) and glycerol to improve its bioavailability. Studies on the stability of this FK480 dosage form revealed that the main degradation occurred by optical isomerization at the asymmetric C-3 position of the pyrrolobenzodiazepine ring. The degradation reaction was accelerated by formic acid formed in a mixture of PEG 400 and glycerol. Addition of amino acids to the capsule solution retarded the isomerization by reacting with formic acid. Therefore, formic acid appears to accelerate optical isomerization of FK480.
MoreTranslated text
Key words
CCK-A receptor antagonist,optical isomerization,polyethylene glycol,formation of formic acid
AI Read Science
Must-Reading Tree
Example
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined