Cyclodextrins pharmaceutically useful

Matthijs, N., Van Hemehyck, S., Maftouh, M., Massart, D.L., Vander Heyden, Y. Electrophoretic separation strategy for chiral pharmaceuticals using highly-snlfated and neutral cyclodextrins based dual selector systems. An. Chim. Acta 2004, 525, 247-263. 

In this chapter, we especially focus on the strategies for enhancement of rectal absorption of various drugs including peptides and proteins from rectal mucosa using pharmaceutically useful excipients, cyclodextrins (CyDs), and the other absorption enhancers. 

Uekama, K. Hirayama, F. Irie, T. Pharmaceutical uses of cyclodextrin derivatives. In High Performance Biomaterials, A Comprehensive Guide to Medical and Pharmaceutical Applications Szyeher, M., Ed. Technomic Lancaster, PA, 1991 789-806. 

Duchene D, Wouessldjewe D. Physicochemical characteristics and pharmaceutical uses of cyclodextrin derivatives, part I. Pharm Technol 1990 14(6) 26, 28, 34. 

Solubilisation by surface-active agents is discussed in Chapter 6. Alternatives to micellar solubilisation (or solubilisation in vesicles) include the use of the cyclodextrin family. When the first edition of this book was published in 1981 (and a diagram of a cyclo-dextrin-dmg complex was used to adorn the cover), the use of cyclodextrins was in its infancy. Attention was then focused around a-, P- and yavailable commercially for pharmaceutical use. Ten per cent of this cyclodextrin can enhance the solubility of betamethasone 118 times, of diazepam 21 times and of ibuprofen 55 times. 

I 14 Pharmaceutical Applications of Cyclodextrins and Their Derivatives Table 14.1. Pharmaceutically Useful CyDs... 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

A good deal of attention recently has been directed towards the use of derivatives of cyclodextrin for the solubilization and stabilization of pharmaceuticals [124 126]. One cautionary note—complexation may adversely affect the dissolution an/or permeability characteristics of the drug, thereby possibly decreasing drug bioavailability. 

Cyclodextrins have ecologically advantageous properties. Not only are they produced from natural and replenishable sources, they are biodegradable, non-toxic and possess no allergenic potential [32,33]. They are commercially available in bulk quantities at an optional degree of purity and have been used for many years in pharmaceuticals. 

As yet, the number of applications is limited but is likely to grow as instrumentation, mostly based on existing CE systems, and columns are improved and the theory of CEC develops. Current examples include mixtures of polyaromatic hydrocarbons, peptides, proteins, DNA fragments, pharmaceuticals and dyes. Chiral separations are possible using chiral stationary phases or by the addition of cyclodextrins to the buffer (p. 179). In theory, the very high efficiencies attainable in CEC mean high peak capacities and therefore the possibility of separating complex mixtures of hundreds of... 

CE has been applied extensively for the separation of chiral compounds in chemical and pharmaceutical analysis.First chiral separations were reported by Gozel et al. who separated the enantiomers of some dansylated amino acids by using diastereomeric complex formation with Cu " -aspartame. Later, Tran et al. demonstrated that such a separation was also possible by derivatization of amino acids with L-Marfey s reagent. Nishi et al. were able to separate some chiral pharmaceutical compounds by using bile salts as chiral selectors and as micellar surfactants. However, it was not until Fanali first showed the utilization of cyclodextrins as chiral selectors that a boom in the number of applications was noted. Cyclodextrins are added to the buffer electrolyte and a chiral recognition may... 

An extremely important aspect in pharmaceutical research is the determination of drug optical purity. The most frequently applied technique for chiral separations in CZE remains the so-called dynamic mode where resolution of enantiomers is carried out by adding a chiral selector directly into the BGE for in situ formation of diastereomeric derivatives. Various additives, such as cyclodextrins (CD), chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles, and ergot alkaloids, are reported as chiral selectors in the literature, but CDs are by far the selectors most widely used in chiral CE. 

Zuo, Z., Kwon, G., Stevenson, B., Diakur, J., and Wiebe, L.I. Flutamide - hydroxypropyl-6-cyclodextrin complex formulation, physiccal characterization, and absorption smdies using the Caco-2 in vitro model. /. Pharm. Pharmaceut. Sci., 3(2) 220-227, 2000. 

Fanali S, Aturki Z, Desiderio C. Enantioresolution of pharmaceutical compounds by capiUary electrophoresis. Use of cyclodextrins and antibiotics. Enantiomer 1999 4 229 1. 

Table 17.3 contains only few examples of where CMPA have been applied for pharmaceutical analysis. The majority of selectors that have been used are different types of cyclodextrines [39,60], but there is also a macrocyclic antibioticum in the list [59]. Guo et al. [59] applied norvancomycin as a CMPA for an assay of (S)-ketoprofen in capsules, the results are displayed in Eigure 17.6B. They... 

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