Document Detail


NMR analysis of ion pair formation between timolol and sorbic acid in ophthalmic preparations.
MedLine Citation:
PMID:  17145156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ion pair formation between timolol and sorbic acid was investigated using NMR spectroscopy in order to clarify their interactions within ophthalmic preparation. (13)C and (1)H NMR spectra of timolol, sorbic acid, and a mixture of the two were obtained, and the signal changes induced by pairing were observed. The carbon signals of the butylaminopropanol moiety of timolol were markedly shifted in the mixture, as were the carboxyl and conjugated carbons assigned to sorbic acid. The localizations of the changes in each molecule revealed the binding sites. The profiles of butylaminopropanol carbon chemical shifts plotted against a molar ratio of sorbate were synchronized, which suggested a single type of interaction with sorbic acid. The Job plot showed a typical pattern with a single-maximum at a mole function of 0.5, indicating the presence of a 1:1 complex of timolol and sorbic acid. The stability constants (K) of the timolol-sorbate and timolol-maleate pairs were 1.9x10(1) and 2.2x10(2)M(-1), respectively. The higher K value of the timolol-maleate interaction suggested that it was dominant to the timolol-sorbate interaction when maleate and sorbate coexisted within a timolol solution. Here, we demonstrated evidence of an interaction between timolol and sorbic acid using simple NMR measurements, which suggested the existence of ion pair formation derived from charge neutralization. Our analysis using NMR spectroscopy should advance the understanding and optimization of formulations that are based on ion pair.
Authors:
Masayo Higashiyama; Katsuhiro Inada; Akira Ohtori; Kazuaki Kakehi
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Publication Detail:
Type:  Journal Article     Date:  2006-12-04
Journal Detail:
Title:  Journal of pharmaceutical and biomedical analysis     Volume:  43     ISSN:  0731-7085     ISO Abbreviation:  J Pharm Biomed Anal     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-26     Completed Date:  2007-04-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309336     Medline TA:  J Pharm Biomed Anal     Country:  England    
Other Details:
Languages:  eng     Pagination:  1335-42     Citation Subset:  IM    
Affiliation:
Senju Pharmaceutical Co. Ltd., 1-5-4 Murotani, Nishi-Ku, Kobe 651-2241, Japan. m-higashiyama@senju.co.jp
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MeSH Terms
Descriptor/Qualifier:
Chromatography, High Pressure Liquid
Ions
Magnetic Resonance Spectroscopy / methods*
Molecular Structure
Octanols / chemistry
Ophthalmic Solutions / analysis*,  chemistry
Sorbic Acid / analysis*,  chemistry
Timolol / analysis*,  chemistry
Water / chemistry
Chemical
Reg. No./Substance:
0/Ions; 0/Octanols; 0/Ophthalmic Solutions; 110-44-1/Sorbic Acid; 26839-75-8/Timolol; 7732-18-5/Water

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


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