Dispersed cyclodextrins

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. 

In these equations, MR3 4, MR, and MR4 are the molar refractivities of 3- and 4-substituents, of R-, and of 4-substituents, respectively. All the equations exhibited positive coefficients of the MR terms. This suggests that the dispersion forces of substituents are actually responsible for the binding of ligands to cyclodextrin. Eq. 14 shows that the stability of a-cyclodextrin-RCOO complexes increases linearly up to MR = 4.0 and then falls off linearly. 

The more useful types of chirally active bonded phases are those based on the cyclodextrins. There are a number of different types available, some of which have both dispersive or polar groups bonded close to the chirally active sites to permit mixed interactions to occur. This emphasizes the basic entropic differences between the two isomers being separated. A range of such products is available from ASTEC Inc. and a separation of the d and / isomers of scopolamine and phenylephrine are shown in figure 4. The separations were carried out on a cyclodextrin bonded phase (CYCLOBOND 1 Ac) that had been acetylated to provide semi-polar interacting groups in close proximity to the chiral centers of the cyclodextrin. The column was 25 cm long, 4.6 mm in diameter and packed with silica based spherical bonded phase particles 5pm in diameter. Most of the columns supplied by ASTEC Inc. have these dimensions and, consequently, provide a... 

Table 10.3 Formation of complexes between cyclodextrins and disperse dyes [42]...

Cl Disperse Yellow 42 Cl Disperse Orange 11 Cl Disperse Orange 29 Cl Disperse Violet 1 Cl Disperse Violet 31 Cl Disperse Blue 56 Cl Disperse Blue 165 Resolin Red FRL (DyStar) Resolin Yellow 5GL (DyStar) With y-cyclodextrin Cl Disperse Orange 11... 

Gotti et al. [42] reported an analytical study of penicillamine in pharmaceuticals by capillary zone electrophoresis. Dispersions of the drug (0.4 mg/mL for the determination of (/q-penicillaminc in water containing 0.03% of the internal standard, S -met hy I - r-cystei ne, were injected at 5 kPa for 10 seconds into the capillary (48.5 cm x 50 pm i.d., 40 cm to detector). Electrophoresis was carried out at 15 °C and 30 kV, with a pH 2.5 buffer of 50 mM potassium phosphate and detection at 200 rnn. Calibration graphs were linear for 0.2-0.6 pg/mL (detection limit = 90 pM). For a more sensitive determination of penicillamine, or for the separation of its enantiomers, a derivative was prepared. Solutions (0.5 mL, final concentration 20 pg/mL) in 10 mM phosphate buffer (pH 8) were mixed with 1 mL of methanolic 0.015% 1,1 -[ethylidenebis-(sulfonyl)]bis-benzene and, after 2 min, with 0.5 mL of pH 2.5 phosphate buffer. An internal standard (0.03% tryptophan, 0.15 mL) was added and aliquots were injected. With the same pH 2.5 buffer and detection at 220 nm, calibration graphs were linear for 9.3-37.2 pg/mL, with a detection limit of 2.5 pM. For the determination of small amounts of (L)-penicillamine impurity, the final analyte concentration was 75 pg/mL, the pH 2.5 buffer contained 5 mM beta-cyclodextrin and 30 mM (+)-camphor-10-sulfonic acid, with a voltage of 20 kV, and detection at 220 nm. Calibration graphs were linear for 0.5-2% of the toxic (L)-enantiomer, with a detection limit of 0.3%. 

The stability constant of complexes between /1-cyclodextrine and p-nitroaniline is higher than that of aniline because the resonace charge delocalization (and London dispersion interactions) is an important factor influencing the stability of these complexes62. This behaviour parallels that of corresponding phenols. 

Of course, encapsulation can also be governed by other factors besides the charge control. Thus, the anion-radical of fullerene Cgg exhibits better inclusion ability with cyclodextrins than neutral Cgg (Liu et al. 2007). Polarizability of the anion-radical is much larger than that of neutral fullerene. This factor enhances dispersion forces and assists encapsulation of the charged particle by cyclodextrin. 

Nalidixic acid is another example of BCS class II drug, with oral bioavailability limited by poor solubility and slow dissolution (40). Compared to drug powder alone, the solid dispersion of nalidixic acid with P-cyclodextrin or PYP or sodium starch glycolate had much faster dissolution. X-ray diffraction studies revealed the formation of amorphous areas and less degree of crystallinity in the solid dispersion of nalidixic acid with excipients. 

A similar chiral environment is given by inclusion to cyclodextrins (CDs), cyclic oligosaccharides (3). The outside of the host molecule is hydrophilic and the inside hydrophobic. The diameters of the cavities are approximately 6 (a), 7-8 (j3), and 9-10 A (7), respectively. Reduction of some prochiral ketone-j3-CD complexes with sodium boro-hydride in water gives the alcoholic products in modest ee (Scheme 2) (4). On the other hand, uncomplexed ketones are reduced with a crystalline CD complex of borane-pyridine complex dispersed in water to form the secondary alcohols in up to 90% ee, but in moderate chemical yields. Fair to excellent enantioselection has been achieved in gaseous hydrohalogenation or halogenation of a- or /3-CD complexes of crotonic or methacrylic acid. These reactions may seem attractive but currently require the use of stoichiometric amounts of the host CD molecules. 

NMR ( H, 13C), mass spectrometry, infrared (IR), and ultraviolet (UV) were used, especially NMR, in studying the complexation interactions of artemisinins with agents, such as /3-cyclodextrin <2004JPS2076> and micellar dispersions of octanoyl-6-O-ascorbic acid <2002JPS2265>. Furthermore, the structure-activity relationship of solution structures of deoxoartemisinin 10a and carboxypropyldeoxoartemisinin 10b, as antitumor compounds, was studied by H and 13C NMR <2000BBR359>. 

Nagarsenker, M. S., R. N. Meshram, and G. Ramprakash (2000). Solid dispersion of hydroxypropyl-fi-cyclodextrin and ketorolac enhancement iofvitro dissolution rates, improvement in antiin ammatory activity and reduction in ulcerogenicity in rdtfharm. Pharmacol., 52 949-956. 

Fukuda, N., Higuichi, N., Ohno, M., Kenmochi, H., Sekikawa, H., andTakada, M. 1986. Dissolution behavior of prednisone from solid dispersion systems with cyclodextrins and polyvinylpyrroliddran. Pharm. 

Table 17.2 illustrates the absolute oral bioavailability of several Danazol formulations nanoparticle dispersion, solubilized cyclodextrin oral formulation, and conventional suspension. Danazol represents a poorly water-soluble compound (H /mL) whose oral bioavailability is dissolution limited. 

A. The infrared absorption spectrum of a potassium bromide dispersion of sample exhibits relative maxima at the same wavelengths as those of a similar preparation of USP beta-Cyclodextrin Reference Standard. 

Skiba, M., Wouessidjewe, D., Fessi, H., Devissaguet, J. R, Duchene, D., and Puisieux, F. (1992), Preparation et utilizations des nouveau systemes colloidaux dispersibles a base de cyclodextrines sous forme de nanocapsules, French Patent 92-07285. 

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