Characterization of the complexation of diflunisal with hydroxypropyl-beta-cyclodextrin.
The equilibrium dialysis method was applied to the determination of drug cyclodextrin stability constants using diflunisal and 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as a model system. Analysis of the data showed the existence of a linear Scatchard plot, indicative of the formation of a 1:1 diflunisal:HPBCD complex. The mean complexation constant (Kc) +/- S.D. was 3,892 +/- 360 M(-1). The stoichiometry of the complex was verified using the appropriate mass action law equation. The diflunisal:HPBCD complex was also investigated using titration microcalorimetry. A Kc of 3,394 M(-1) was obtained together with an enthalpy change (deltaH) of -20.76 kJ/mol(-1). The Kc values obtained here using the equilibrium dialysis and microcalorimetric methods were comparable to one reported previously using a potentiometric method (5,564 +/- 56 M(-1)).
Ugwu
S O
SO
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Alcala
M J
MJ
Bhardwaj
R
R
Blanchard
J
J
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods; D003505:Cyclodextrins / Q000032:analysis / Q000737:chemistry*; D003956:Dialysis / Q000379:methods; D004061:Diflunisal / Q000032:analysis / Q000737:chemistry*; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry; D013816:Thermodynamics; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004061:Diflunisal