A novel formulation of ketoconazole entrapped in alginate with anionic polymer beads for solubility enhancement: Preparation and characterization

Abstract

Ketoconazole has low solubility in intestinal pH, whereas drug absorption is largest in the small intestine, which can reduce the bioavailability of the drug. Alginate can be combined with a suitable polymer and cross-linked with divalent ions and another polymer to enhance the solubility of the drug. Ketoconazole could be loaded into a matrix polymer consisting of alginate and anionic polymer through hydrogen bonds formed with the N atom of the ketoconazole. The method employed to produce ketoconazole beads involved ionic gelation with CaCl2 as a cross- linking agent, and various polymer combinations were used: alginate 100:0 (AL100), alginate:pectin 75:25 (AP75) and 50:50 (AP50), alginate:gum acacia 75:25 (AG75) and 50:50 (AG50), and alginate:carrageenan 75:25 (AK75) and 50:50 (AK50). The beads were characterized by using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), swelling study, in vitro drug release study, and solubility determination. The incorporation of ketoconazole into combination matrices of AL100, AG75, AP75, AP50, and AK75 resulted in significantly higher solubility in FaSSIF-2X (Fasted State Simulated Intestinal Fluid) at pH 6.5 compared to pure ketoconazole.