Solid-state characterizations of the inclusion complexes between warfarin sodium and β-cyclodextrin

Abstract

The sodium salt of warfarin has become the most widely used in order to improve the physicochemical properties of warfarin such as solubility, dissolution rate and mechanical properties. Nevertheless, warfarin sodium may be precipitated in the gastrointestinal tract leading to erratic in drug absorption. The purpose of this study is to investigate the inclusion complexes between β-CD and warfarin sodium by spray drying technique. The inclusion complexes were prepared at various β-CD and warfarin sodium mole ratio of 1:0.5, 1:1 and 1:1.5. The inclusion complexes were characterized by Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and X-ray Diffractrometer (XRD). The presence of warfarin sodium in the inclusion complexes was confirmed when the bands of C=O vibration of warfarin sodium (1670 cm-1, 1610cm-1) were shifted upon inclusion complex compared to the bands in the free warfarin sodium (1720cm-1, 1660cm-1). In the 1H NMR spectrum of the β-CD-warfarin sodium (β-CD-WNa) inclusion complexes, the upfield shift of the protons lying on the inner surface of β-CD (H-3, H-5 and H-6) results from shielding effects, suggesting that warfarin sodium was included into the cavity of β-CD. These results confirmed the presence of the inclusion of warfarin sodium into the β-CD cavity. Furthermore, the morphology of spray dried powders was investigated by using SEM. The spray dried powder appeared in spherical shape with roughness.