Cyclodextrins as solubilising agents

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 y yclodextrins, but a veritable industry has grown up with an array of derivatives which can lend useful new properties to the complexes they form. There is now Encapsin HPB (hydroxypropyl-/3-cyclodextrin), which is available 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. 

Not all cyclodextrins are free of adverse effects di-O-methyl /i-CD, for example, has a strong affinity for cholesterol and is haemolytic. It is also one of the hest solubilisers technically. 

Reproduced from K. Harata and H. Uedaira, Bull. Chem. Soc. Jpn., 48, 375 0975.  

Hgure 5.9 Molecular structures of (a) nifedipine and (b) 4-sulfonic colix[n]arenes. As n increases (4, 6, 8) the cavity size (see (c)) increases from 0.3 nm, through 0.76 nm to 1.16 nm. The solubility increase for nifedipine is greatest with calix[8]arene, being nearly 250% at a concentration of 0.008 mol dm and pH of 5. 

Reproduced from Yang and de Villiers, Eur. J. Pharm. Biopharm., 58, 629-636 (2004). 

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