Preparation and Evaluation of Inclusion Complex of the Lipid Lowering Drug Lovastatin with β-Cyclodextrin

Abstract

Several attempts have been made to improve the solubility of water insoluble drugs. Over the years, inclusion complexation of drugs with β-cyclodextrin has emerged as a viable attempt to improve the dissolution of water insoluble drugs. The aim of the present work was to improve the dissolution rate of lovastatin, a water insoluble drug, by inclusion complexation with β-cyclodextrin. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of lovastatin with β-cyclodextrin was 1:1. The solubility of lovastatin increased with increasing amount of β-cyclodextrin in water. Gibbs free energy (ΔGtr°) values were all negative, indicating the spontaneous nature of lovastatin solubilization. Complexes of lovastatin were prepared with β-cyclodextrin by various methods such as kneading, coevaporation and physical mixing. The complexes were characterized by Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) patterns. These studies indicated the inclusion of lovastatin in the cavity of β-cyclodextrin. The complexation resulted in a marked improvement in the solubility of lovastatin. The complex prepared by kneading method showed fastest and highest in vitro dissolution rate compared to the tablets of pure of lovastatin. Physical mixture of β-cyclodextrin/lovastatin also showed significant improvement in the dissolution rate compared to pure lovastatin. Mean dissolution time (MDT) of lovastatin decreased significantly after preparation of complexes and physical mixture of lovastatin with β-cyclodextrin. Similarity factor (f2) indicated significant difference between the release profiles of lovastatin from complexes and from pure lovastatin.