Beta-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs

Introduction Poor solubility of API is one of the biggest challenges in drug development: a large number of drugs on the market (approximately 40%), and even more those under development (approx. 70%), belong to class II, or respectively class IV of the BCS and are therefore associated with solubility and consequently poor oral bioavailability. Aim To assess the potential of a series of novel β-cyclodextrin (βCD)-dextran polymers for drug delivery. Method Size analysis of a series of βCD-dextrans was measured by size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4). Stability of model drug/βCD-dextrans was assessed by isothermal titration calorimetry (ITC). For evaluation of the solubilization efficiency, phase-solubility diagrams were made employing hydrocortisone as a model of poorly soluble drugs whereas reverse dialysis was used to detect potential drug true supersaturation as well as controlled release effects. Results Results indicate that all investigated βCD-polymers are of appropriate sizes for parenteral administration. Thermodynamic results demonstrate that the presence of the dextran backbone structure does not affect the stability of the βCD/drug complex, compared to native βCD and commercially available derivatives. Solubility studies evidence higher solubilizing abilities of these new polymers in comparison to commercially available βCDs (Fig. 1, a). Moreover, drug release studies evidenced that diffusion of HC was influenced by the solubilization induced by the βCD-derivatives (Fig. 1, b).