Cubosomes as oral drug delivery systems: A promising approach for enhancing the release of clopidogrel bisulphate in the intestine

Abstract

Clopidogrel bisulphate (CB) is a first line antiplatelet drug for treatment of myocardial infarction and stroke. Yet, its efficacy is limited by its poor solubility in intestinal pH, its main site of absorption. The main aim of this study is to enhance the intestinal release of CB by loading in cubosome nanoparticles. Glyceryl monooleate (GMO) based CB loaded cubosomes were prepared using a 33 factorial design to study the effect of polyvinyl alcohol (PVA), poloxamer 407 (PL407) concentrations and ratio of CB to the disperse phase on the average particle size, entrapment efficiency (%EE), in vitro release at 15min (%Q15), and their morphology using transmission electron microscopy (TEM). The release of the optimized formula was compared in buffer transition media (pH 1.2 for 2h then pH 6.8 for 6h) to free drug to study the effect of the changing pH in the gastrointestinal tract (GIT) on CB release. The antihaemostatic properties of the optimized formula were compared to the commercial product Plavix using bleeding time (BT) model in rabbits. The prepared cubosomes were in the nano range (115 6.47 to 248 4.63nm) with high %EE (91.22 4.09% to 98.98 3.21%). The optimized formula showed significantly higher (p<0.05) CB release in intestinal pH and preserved the high% released (95.66 1.87%) in buffer transition release study compared to free drug (66.82 4.12%) as well as significantly (p<0.05) higher antihaemostatic properties with longer BT (628.47 6.12s) compared to Plavix (412.43 7.97s). Thus, cubosomes proved to be a successful platform to enhance the intestinal release of CB and improve its absorption. 2018 The Pharmaceutical Society of Japan.