Ternary cyclodextrin complexes

Keywords Cydodextrins complexation, ternary cyclodextrin complexes, lipophilic drugs, water-soluble polymers... 

In this chapter it was considered worthy of interest to quote those reports where solubility, dissolution, and/or pharmacokinetic studies have been performed on prepared ternary cyclodextrin complexes to correlate the dissolution with in-vivo exposure. 

The binary and ternary cyclodextrin complexes of vinpocetine (a poorly water-soluble base-type drug with significant peripheral vasodilator effect) with P-CD and HP-P-CD in the absence and prescence of HPMC (0.1% w/v) or PVP (0.25% w/v) have... 

Mir, M., Marquet, J., and Cay6n, E., Solid state photochemistry of ternary cyclodextrin complexes total selectivity in the photoreduction of nitrophenyl ethers by 1-phenylethylamine, Tetrahedron Lett., 33, 7053, 1992. 

Synergistic effects in terms of efficiency of CE enantioseparation have been observed when a second (not necessarily chiral) selector is added in the same buffer system. It has been demonstrated that a combination of 18-crown-6 and )-cyclodextrin can achieve or enhance enantioselective separations of nonpolar amines, which are rarely observed with cyclodextrins alone <1997JCH(781)129, 1997JCH(695)157>. The formation of a ternary sandwich complex (dual complex) is postulated to be responsible for such a beneficial effect. 

FIGURE 1 Molecular structures of I, II, and a-cyclodextrin (a-CD) alkoxide. Schematic representation of the inclusion complexes and reaction intermediates involved in the hydrolysis of I affording acetic acid and m-ferf-butyl phenol. The inset shows the CAChe-minimized structure of the ternary catalytic complex I C a-CD alkoxide-ll proposed by Bender et al. (7S). The putative hydrogen bond between the alkoxide of a-CD and II is indicated by a solid line. a-CD alkoxide is shown in stick representation, and only polar hydrogen atoms are specified. I is shown in CPK representation and II in ball and stick. (See Color Insert in the back of this book.)... 

Ono, N. Hirayama, F. Arima, H. Uekama, K. Determination of stability constant of P-cyclodextrin complexes using the membrane permeation technique and the permeation behavior of drug-competing agent-P-cyclodextrin ternary systems. Eur. J. Pharm. Sci. 1999, 8 (2), 133-139. 

The structure of the ternary inclusion complex composed of 3-cyclodextrin, phenol, and, chloroform or carbon tetrachloride, formed in the reaction mixture, is determined by NMR spectroscopy. The selective catalysis by cyclodextrin was attributed to the regulation of molecular conformation of substrates with respect to dichlorocarbene, to trichloromethy1 cation, or to allyl cation in the ternary molecular complex. 

Formylations of phenol, resorcinol and indole, dichloromethylations of 4-methylphenol and 5,6,7,8-tetrahydro-2-naphthol, carboxylation of phenol, and allylation of 2,4,6-trimethylphenol proceed site-selec-tively in high yields by using 3-cyclodextrin as catalyst. The formation of ternary inclusion complex composed of cyclodextrin, substrate, and dichlorocarbene, trichloromethyl cation or allyl cation in the reaction mixture is an important factor of the site-selective reactions. The cyclodextrin is also effective by limiting the molecular size of the reaction intermediate. 

In this reaction in cyclodextrin, the transition state should involve the ternary molecular complex composed of microcrystalline cyclodextrin complex and a fixed gaseous reagent in it. Hadjoudis, et also sug-... 

Great attention should be paid for the basic investigation and useful application of parent cyclodextrins themselves. Cyclodextrin can interact with two kinds of solutes A and B in water to form a a ternary inclusion complex, CD A B leading to specific condensation of two solutes to form... 

Role of Polymers in Ternary Drug Cyclodextrin Complexes 415... 

The use of water-soluble polymers in ternary CD complexes has also been utilized for controlling the rate of release of drug from cyclodextrin formulation. It seems that ternary complexes consisting of polymers as ternary component with low viscosity (PVP) tend to dissolve rapidly [25], while polymers with matrix-forming property (HPMC) lead to sustained drug release [26] in comparison to corresponding binary systems. 

In another work [35], the same workers have reported cyclodextrin complexes of vinpocetine with SBEp-CD in the presence and absence of PVP (0.25% w/v) and HPMC (0.10% w/v). In this study the values of Kc (Table 12.3) also increased with the addition of water-soluble polymers to complexation medium, in comparision to binary system, indicating higher complexation effeciency and solubilization effect of SBEp-CD toward vinpocetine in ternary complexes. 

Increased para selectivity has been reported by using potassium, cesium and ammonium hydroxide as bases instead of sodium hydroxide.The addition of 6-cyclodextrin (BCD) afforded 100% para selectivity due to formation of a preferentially para ternary molecular complex between the phenolate ion, BCD and the dichlorocarbene intermediate.Although the presence of BCD does not enhance the total aldehyde production, it reduces the proportion of other isomeric aldehydes formed in favour of the para-product. Recently Zhang et. reported the synthesis of p-... 

Recently, a ternary complex of cytochrome c with a polyanionic /1-cyclodextrin has been reported (85). A self-assembled supra-molecular bidentate N,P ligand for aqueous organometallic catalysis was also described (86). Although related, such systems are out of the scope of this review and will not be discussed further here. 

In analogy to the carboxylate binding by zinc-containing cyclodextrin 10 (see Sect. 2), Lewis acidic centers such as a copper(II) histamine unit may also serve for the chelation of the (deprotonated) 2-aminoacetate substructure of a-amino acids [51], Rizzarelli, Marchelli et al. used a respective j8-cyclodextrin derivative for the formation of the ternary complexes 36 and 37 with racemic... 

In another study, it was successfully reported an intimate ternary blend system of poly(carbonate) (PC)/poly(methyl methacrylate ) (PMMA)/poly (vinyl acetate) (PVAc) obtained by the simultaneous coalescence of the three guest polymers from their common y-cyclodextrin (y-CD) inclusion complex (IC). The thermal transitions and the homogeneity of the coalesced ternary blend were studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) [50]... 

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