Fabrication of Oral Sustained Release Capecitabine Loaded Nanostructured Lipid Carriers

Abstract

The purpose of this study was to sustain the release of capecitabine (CAP) and to improve its overall pham1acokinetic profile by incorporating it inside of nanostructured lipid carriers (NLCs) using micro-emulsion method to fabricate capecitabine loaded NLCs (CAP-NLCs). CAP belongs to BCS-I drug class readily absorbed from GIT, having a very short half-life of30 to 60 min. CAP-NLCs were optimized using Design Expert®. The optimized CAP-NLCs constitute of7.5 mg CAP, 80 mg Precirol® ATO 5, 30 mg Labrafil® M 1944 CS, and 1.5% Tween® 80 solution. The characterizations of various constraints of CAP-NLCs were then perfonned including particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), fourier transfonn infrared (FTIR), X-ray diffraction (XRD) and uv-visible spectroscopy. In vitro release study, in vivo phannacokinetic study, and histopathological evaluation were performed. The optimized CAP-NLCs exhibited minimum mean PS of 158.75 ± 1.75 run, low PDI of 0.195 ± 0.010, ZP of 16.90 ± 0.90 mY and high EE of85.5 1 ± 0.37%. TEM results indicated smooth surface NLCs, spherical in shape, and size in nano range. FTIR results concluded no chemical interactions among the components. XRD analysis implied the amorphous structure of CAP-NLCs. In comparison to the CAP-Solution, CAP-NLCs provided a sustained release pattem. In vivo phannacokinetic study demonstrated that overall pharmacokinetic profile was improved with many folds increase in the half-life (t 1l2), mean residence time (MRT), and area under the curve (AUC). Histopathological evaluation indicated that the tissues of the major organs were intact with no significant change in tissues nonnal texture. The results concluded that NLCs could be capable nanocaniers for administration of CAP orally with sustained release pattem, improved pharmacokinetic parameters, and better safety profile.