Sulfobutyl ether-alkyl ether mixed cyclodextrin derivatives with enhanced inclusion ability

• Published in: Journal of pharmaceutical sciences Vol. 98; no. 12; pp. 4769 - 4780
• Main Authors: Tongiani, Serena, Ozeki, Tetsuya, Stella, Valentino J.
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.12.2009; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Algorithms; Animals; beta-Cyclodextrins - chemistry; binding constants; Biological and medical sciences; calcium channel blockers; Calcium Channel Blockers - chemistry; Cyclodextrins - chemistry; Dihydropyridines - chemistry; Erythrocytes - drug effects; Erythrocytes - ultrastructure; Ethers - chemistry; General pharmacology; Hemolysis; inclusion complex; Medical sciences; modified cyclodextrins; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; phase solubility; Rabbits; Solubility; Spectrophotometry, Ultraviolet; steroids; Steroids - administration & dosage; Steroids - chemistry; surface activity; Surface Tension; UV absorbance; inclusion complex; calcium channel blockers; surface activity; steroids; binding constants; modified cyclodextrins; UV absorbance; phase solubility; hemolysis; Hemolysis; Binding; Steroid; Pharmaceutical technology; Ether; Calcium antagonist; Solubility; Absorbance; Cyclodextrin; Alkyl; Inclusion compound; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21791

The aim of this work was to study the complexation capability of new sulfobutyl ether-alkyl ether (SBE-AE-CD) mixed β- and γ-cyclodextrin derivatives with a series of structurally related steroids (6α-methylprednisolone, prednisolone, triamcinolone, D(−) norgestrel and hydrocortisone) and a number of dihydropyridine calcium channel blockers (nimodipine, nitrendipine, nifedipine) that traditionally interact poorly with other cyclodextrins (CDs). The effect of the total degree of substitution (TDS) and of the length of the alkyl side chain on binding capacity of these new modified CDs was evaluated as was their ability to induce red blood cell hemolysis. An attempt was made to correlate hemolysis to surface activity. Binding constants between the SBE-AE-CDs and selected molecules were determined by spectroscopic studies, and only in few cases by solubility studies. Hemolysis percentage was determined using citrated rabbit blood and citrated human blood with UV analysis. The surface activity was measured with a tensiometer. A significant improvement in the binding capacity between various substrates and the new SBE-AE-CDs was observed when compared to the SBE-CDs. The length of the alkyl chain and total degree of alkylation affected the binding with the relationship being complex. For most compounds, an intermediate degree of substitution appeared to be advantageous. The hemolysis studies showed that some of the derivatives may induce hemolysis and this correlated with higher surface activity for some but not all of the derivatives. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4769–4780, 2009