Cyclodextrin complexation, stabilizing

KA Connors. Population characteristics of cyclodextrin complex stabilities in aqueous solution. J Pharm Sci 84 843-848, 1995. 

Matsui and Mochida24) have determined the thermodynamic stabilities (log 1 /Kd) for a- and P-cyclodextrin complexes with a variety of alcohols (Table 2) and analyzed the results in connection with the physicochemical properties of the guest molecules by the multivariate technique. The log 1/Kd values were plotted against log Pe, where Pe is the partition coefficient of alcohol in a diethyl ether-water system. The plots for the a- and P-cyclodextrin complexes with eight 1-alkanols gave approximately straight lines with slopes of around one. 

Upon formulating these relationships, phenols with branched alkyl substituents were not included in the data of a-cyclodextrin systems, though they were included in (3-cyclodextrin systems. In all the above equations, the n term was statistically significant at the 99.5 % level of confidence, indicating that the hydrophobic interaction plays a decisive role in the complexation of cyclodextrin with phenols. The Ibrnch term was statistically significant at the 99.5% level of confidence for (3-cyclo-dextrin complexes with m- and p-substituted phenols. The stability of the complexes increases with an increasing number of branches in substituents. This was ascribed to the attractive van der Waals interaction due to the close fitness of the branched substituents to the (3-cyclodextrin cavity. The steric effect of substituents was also observed for a-cyclodextrin complexes with p-substituted phenols (Eq. 22). In this case, the B parameter was used in place of Ibmch, since no phenol with a branched... 

The results were simple and clear-cut Only the two terms ofa° and Emin were involved for the a-cyclodextrin systems, and the two terms of k and Emin, for (S-cyclodextrin systems. This means that the stabilities of the inclusion complexes are mainly governed by the electronic and steric interactions in a-cyclodextrin systems and by the hydro-phobic and steric interactions in (i-cyclodextrin systems, regardless of the position of the substituents in the phenols. These observations agree well with those by Harata23), who showed that there is no appreciable difference in thermodynamic parameters between cyclodextrin complexes of m- and p-di substituted benzenes and that the contribution of the enthalpy term to the complexation is more significant in a-cyclodextrin systems than in P-cyclodextrin systems, where the inhibitory effect... 

Tpnnesen, H.H, Masson, M., and Loftsson, T., Studies on curcumin and curcuminoids. XXVII. Cyclodextrin complexation solubility, chemical an photochemical stability, Int. J. Pharm., 244, 127, 2002. 

Cross-interaction constants and transition-state structure in solution, 27, 57 Crown-ether complexes, stability and reactivity of, 17,279 Crystallographic approaches to transition state structures, 29,87 Cyclodextrins and other catalysts, the stabilization of transition states by, 29,1... 

Cyclodextrin can also be used in order to stabilize monomers that would otherwise oxidize upon contact with air. The cyclodextrin host shields the monomer from oxygen in the air. Monomers such as pyrrole can be stored as a cyclodextrin complex for months without any noticeable degradation. The complex is a colorless powder that does not change color over time unlike pure pyrrole, which would oxidize and therefore turn black via yellow. Another advantage of the method is the fact, that the complex is odorless whereas pyrrole itself has an unpleasant smell. 

Let us compare the methods applied by Pedersen for establishing the complex formation with a modern approach. Today tedious solubility studies are carried out almost exclusively with practical applications in mind, but they are not performed to prove the complex formation. For instance, one ofthe main reasons for the use of cyclodextrin complexes in the pharmaceutical industry is their solubilizing effect on drugs [8]. There, and almost only there, solubility studies are a must. As concerns spectroscopic methods, at present the NMR technique is one ofthe main tools enabling one to prove the formation of inclusion complex, carry out structural studies (for instance, making use of the NOE effect [9a]), determine the complex stability [9b, c] and mobility of its constituent parts [9d]. However, at the time when Pedersen performed his work, the NMR method was in the early stage of development, and thus inaccurate, and its results proved inconclusive. UV spectra retained their significance in supramolecular chemistry, whilst at present the IR method is used to prove the complex formation only in very special cases. 

The present paper is intended to provide a survey on the stabilizing effects of cyclodextrin complexation. Beyond this,other practical consequences of the molecular entrapment of flavors will also be mentioned. 

Long term storage stability tests of flavor beta-cyclodextrin complexes under "non-stress" conditions at room temperature showed that molecular encapsulation in most cases provided an almost perfect preservation of flavors upon ten years storage. The degree of preserving power of cyclodextrin complexation is expressed using a comparison of total flavor content of complexed flavor samples deteimined in 1977 and 1987,respectively./Table IV./... 

A review with ca 500 references has appeared on the stability of cyclodextrin complexes in solution. The principal headings in it are nature of cyclodextrins (CDs) binding equilibria and kinetics strengths of CD complexes structures of CD complexes sources of CD complex stability and prediction of CD stability.168... 

Connors, K. A. 1997. The stability of cyclodextrin complexes in solutfihem. Rev97 1325-1357. 

Takahashi, T., et al. 1986. Stabilization of AD-1590, a non-steroidal antiinflammatory agent, in suppository bases by (3-cyclodextrin complexation. Chem Pharm Bull 34 1770. 

Tirucherai, G.S., and A.K. Mitra. 2003. Effect of hydroxypropyl beta cyclodextrin complexation on aqueous solubility, stability, and corneal permeation of acyl ester prodrugs of gancyclovir. AAPS Pharm Sci Tech 4 E45. 

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