Novel CD-Based Drug Delivery System

Abstract

Enhanced cyclodextrin (CD) complexation can be obtained by adding small amount of some water-soluble polymer to an aqueous complexation medium followed by heating, for example in an autoclave, to 120 to 140°C for 20 to 40 minutes. The water-soluble polymers participate directly in the complex formation, through formation of ternary complexes (or co-complexes), increasing the apparent stability constants of the drug-CD complexes. The ternary complexes possess physicochemical properties that are different from those of regular CD complexes. First, enhanced complexation increases the solubilizing properties of the CDs which reduces the total amount of CD needed to solubilize a given amount of drug. Second, each polymer molecule is able to form complexes with many drug and CD molecules. These large ternary complexes appear to be adsorbed to the surfaces of biological membranes such as to the surface of the skin or the eye, ensuring better contact between the drug molecules and the biological membranes. This results in enhanced drug delivery to the membranes and, consequently, enhanced drug bioavailability. Third, in some cases drug dissolution from solid ternary complexes is faster than from simple CD complexes. Less CD is needed in the ternary complexes and this can, at least partly, explain the faster drug dissolution observed. Finally, through polymer-CD complexation the water-soluble polymers increase the aqueous solubilities of the parent CDs without decreasing their abilities to form complexes with drugs. This will make the parent CDs, such as βCD, more attractive as pharmaceutical excipients.