Determination of binding affinity for chenodeoxycholate in equilibrium with sulfobutylether-β-cyclodextrin.
ABSTRACT A kinetic dialysis technique together with a radiolabeled chenodeoxycholate (CDC) was used to determine the existence of a relationship between the monomer concentration of CDC and the total CDC concentration in different CDC solutions containing 1 or 5 mM sulfobutylether (SBE)-β-cyclodextrin. On the basis of the nature of the relationship and a binding model with binding constants of K₁ and K₂, the binding affinity for the solutions was quantified at the best curve fitting using a least-squares technique. The very high binding affinity of K₁ and the very low (i.e., negligible) binding affinity of K₂ indicate the formation of 1:1 inclusion complexes. In addition, the values of K₁ and K₂ were reasonably interpreted. Similar analysis showed that the formation of 1:2 inclusion complexes and the self-association of the SBE-β-cyclodextrin molecules in the solutions are unlikely. The present study provides a basis for investigating the self-association, quantifying the binding affinity, and interpreting the quantified values.
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ABSTRACT: Cyclodextrins are cyclic oligosaccharides which have recently been recognized as useful pharmaceutical excipients. The molecular structure of these glucose derivatives, which approximates a truncated cone or torus, generates a hydrophilic exterior surface and a nonpolar cavity interior. As such, cyclodextrins can interact with appropriately sized molecules to result in the formation of inclusion complexes. These noncovalent complexes offer a variety of physicochemical advantages over the unmanipulated drugs including the possibility for increased water solubility and solution stability. Further, chemical modification to the parent cyclodextrin can result in an increase in the extent of drug complexation and interaction. In this short review, the effects of substitution on various cyclodextrin properties and the forces involved in the drug-cyclodextrin complex formation are discussed. Some general observations are made predicting drug solubilization by cyclodextrins. In addition, methods which are useful in the optimization of complexation efficacy are reviewed. Finally, the stabilizing/destabilizing effects of cyclodextrins on chemically labile drugs are evaluated.Journal of Pharmaceutical Sciences 11/1996; 85(10):1017-25. · 3.13 Impact Factor
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ABSTRACT: The objective of this review is to summarize recent findings on the safety profiles of three natural cyclodextrins (alpha-, beta- and gamma-CDs) and several chemically modified CDs. To demonstrate the potential of CDs in pharmaceutical formulations, their stability against non-enzymatic and enzymatic degradations in various body fluids and tissue homogenates and their pharmacokinetics via parenteral, oral, transmucosal, and dermal routes of administration are outlined. Furthermore, the bioadaptabilities of CDs, including in vitro cellular interactions and in vivo safety profiles, via a variety of administration routes are addressed. Finally, the therapeutic potentials of CDs are discussed on the basis of their ability to interact with various endogenous and exogenous lipophiles or, especially for sulfated CDs, their effects on cellular processes mediated by heparin binding growth factors.Journal of Pharmaceutical Sciences 03/1997; 86(2):147-62. · 3.13 Impact Factor
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ABSTRACT: The goal of this study was to evaluate alternative salt forms of (SBE)7M-beta-CD (currently the sodium salt). The potential salt form would ideally decrease the rate of (SBE)7M-beta-CD release from osmotic pump formulations and result in an increase in the rate and extent of drug release in osmotic pump tablet and pellet dosage forms. Several (SBE)7M-beta-CD salt forms (potassium, calcium, and two ethylene diamine salt forms) were prepared by either titration or ultrafiltration and characterized by elemental analysis and capillary electrophoresis, CE. The physical properties (water uptake behavior, osmolality, complexation characteristics, etc.) were then compared to the sodium salt form. Although the water isotherm and the binding characteristics using various model drugs were similar among all the salt forms, the calcium salt form appeared to be the best alternative candidate due to its lower osmolality and slower intrinsic dissolution rate.International Journal of Pharmaceutics 03/2007; 330(1-2):73-81. · 3.46 Impact Factor