Cyclodextrins in Dispersed Systems

Laury Trichard, Dominique Duchene, and Amelie Bochot 15.1 

One of the major problems encountered with dispersed systems appears during their preparation, and often results from poor water solubility of drugs leading to either a low yield in drug loading or a slow or incomplete release of the drug. In order to overcome these drawbacks, several authors have proposed the use of cyclodextrins (CyDs) in the formulation of these systems. Alternatively, CyDs themselves can be employed as raw materials for particle preparation, instead of polymers and lipids. 

The first part of this chapter presents dispersed systems involving CyDs, and the methods employed in the preparation of these carriers. The second part details the advantages and potentialities of CyDs associated with dispersed systems, focusing on the different roles of CyDs in such systems. The advantages of simple inclusion complexes involving CyDs in drug administration have been presented in Chapter 14. 

Throughout the chapter, reference should be made to Table 15.1, which is placed before the references. 

Cyclodextrins and Their Complexes. Edited by Helena Dodziuk Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31280-3 

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Peak levels of the drug were observed at 4-6 h postadministration in the cases of the solid dispersion systems. In the case of dicumarol crystal powder, peak levels were observed at 2 to 12 hours postadministration. Average AUC values (0 8 h) of dicumarol following the administration of the dicumarol-PVP solid dispersion systems were 3.31 times (coevaporation method) and 1.54 times (freeze-drying method) that of control. The corresponding numbers for p-cyclodextrin dispersions were 2.18 and 1.72. 

In this equation, AG°CS is taken to be negligible for p- and y-cyclodextrin systems and to be constant, if there is any, for the a-cyclodextrin system. The AG W term is virtually independent of the kind of guest molecules, though it is dependent on the size of the cyclodextrin cavity. The AG dw term is divided into two terms, AG°,ec and AGs°ter, which correspond to polar (dipole-dipole or dipole-induced dipole) interactions and London dispersion forces, respectively. The former is mainly governed by the electronic factor, the latter by the steric factor, of a guest molecule. Thus, Eq. 2 is converted to Eq. 3 for the complexation of a particular cyclodextrin with a homogeneous series of guest molecules ... 

Matsui75) has computed energies (Emin) which correspond to the minimal values of Evdw in Eq. 1 for cyclodextrin-alcohol systems (Table 2). Besides normal and branched alkanols, some diols, cellosolves, and haloalkanols were involved in the calculations. The Emi values obtained were adopted as a parameter representing the London dispersion force in place of Es. Regression analysis gave Eqs. 9 and 10 for a- and P-cyclodextrin systems respectively. 

The master retention equation of the solvation parameter model relating the above processes to experimentally quantifiable contributions from all possible intermolecular interactions was presented in section 1.4.3. The system constants in the model (see Eq. 1.7 or 1.7a) convey all information of the ability of the stationary phase to participate in solute-solvent intermolecular interactions. The r constant refers to the ability of the stationary phase to interact with solute n- or jr-electron pairs. The s constant establishes the ability of the stationary phase to take part in dipole-type interactions. The a constant is a measure of stationary phase hydrogen-bond basicity and the b constant stationary phase hydrogen-bond acidity. The / constant incorporates contributions from stationary phase cavity formation and solute-solvent dispersion interactions. The system constants for some common packed column stationary phases are summarized in Table 2.6 [68,81,103,104,113]. Further values for non-ionic stationary phases [114,115], liquid organic salts [68,116], cyclodextrins [117], and lanthanide chelates dissolved in a poly(dimethylsiloxane) [118] are summarized elsewhere. 

The most common chiral additives used in chiral capillary electrophoresis with micellular solutions (mostly micelles of sodium dodecylsulphate) are derivatives of the three basic cyclodextrins. This system might be considered more of a chromatographic process than one that is electrophoretic, as the solutes are distributed between the aqueous electrolyte phase and the cyclodextrin/micelle phase. The derivatized cyclodextrin additive will also be distributed between the electrolyte and the micelles, the extent of which will depend on the type of derivatized cyclodextrin and its capacity for dispersive or polar interactions with the micelles. As the cyclodextrin additive itself partitions between the electrolyte and the micelle (albeit the distribution under certain circumstances may be small) some of the chiral additive will be distributed on the micelle surface and will act as a chiral stationary phase. 

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