Document Detail

Bupivacaine salts of diflunisal and other aromatic hydroxycarboxylic acids: aqueous solubility and release characteristics from solutions and suspensions using a rotating dialysis cell model.
MedLine Citation:
PMID:  16087321     Owner:  NLM     Status:  MEDLINE    
In the search for poorly soluble bupivacaine salts potentially enabling prolonged postoperative pain relief after local joint administration in the form of suspensions the solubility of bupivacaine salts of diflunisal and other aromatic hydroxycarboxylic acids were investigated together with the release characteristics of selected 1:1 salts from solutions and suspensions using a rotating dialysis cell model. The poorest soluble bupivacaine salts were obtained from the aromatic ortho-hydroxycarboxylic acids diflunisal, 5-iodosalicylic acid, and salicylic acid (aqueous solubilities: 0.6-1.9 mM at 37 degrees C). Diffusant appearance rates in the acceptor phase upon instillation of solutions of various salts in the donor cell applied to first-order kinetics. Calculated permeability coefficients for bupivacaine and the counterions diflunisal, 5-iodosalicylic acid, and mandelic acid were found to be correlated with the molecular size of the diffusants. Release experiments at physiological pH involving suspensions of the bupivacaine-diflunisal salt revealed that at each sampling point the diflunisal concentration exceeded that of bupivacaine in the acceptor phase. However, after an initial lag period, a steady state situation was attained resulting in equal and constant fluxes of the two diffusants controlled by the permeability coefficients in combination with the solubility product of the salt. Due to the fact that the saturation solubility of the bupivacaine-salicylic acid salt in water exceeded that of bupivacaine at pH 7.4, suspensions of the latter salt were unable to provide simultaneous release of the cationic and anionic species at pH 7.4. The release profiles were characterised by a rapid release of salicylate accompanied by a much slower appearance of bupivacaine in the acceptor phase caused by precipitation of bupivacaine base from the solution upon dissolution of the salt in the donor cell.
Jesper Østergaard; Susan W Larsen; Henrik Parshad; Claus Larsen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  26     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-09-14     Completed Date:  2005-11-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  280-7     Citation Subset:  IM    
Department of Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark.
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MeSH Terms
Bupivacaine / chemistry*
Chromatography, High Pressure Liquid
Diflunisal / chemistry*
Hydrogen-Ion Concentration
Hydroxybenzoic Acids / chemistry
Salicylic Acid / chemistry
Reg. No./Substance:
0/Hydroxybenzoic Acids; 0/Solutions; 0/Suspensions; 2180-92-9/Bupivacaine; 22494-42-4/Diflunisal; 69-72-7/Salicylic Acid; 99-06-9/3-hydroxybenzoic acid

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

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