Bioavailability enhanced clopidogrel -loaded solid SNEDDS: Development and in-vitro/in-vivo characterization

Abstract

The purpose of this study is to develop solid self-nanoemulsifying drug delivery systems (S-SNEDDS) for oral bioavailability enhancement of Clopidogrel (CLP). CLP is an anti-platelet drug used to prevent heart strokes. It suffers from low bioavailability due to extensive hepatic metabolism. Two pseudo-ternary phase diagrams were constructed using different oils, bioenhancing surfactants and co-surfactants. SNEDDS were evaluated for their globule size, polydispersity index and in-vitro drug release. The optimum SNEDDS were adsorbed onto Aeroperl®300 to produce S-SNEDDS. Results showed that SNEDDS-8 (SII8) consisting of 10% Capryol™90, 10% Cremophore®EL and 80% Transcutol®HP possessed the smallest globule size and high % drug release. Furthermore, the optimum S-SNEDDS formula was characterized using differential scanning calorimetry and Fourier Transform Infra-Red which indicated that CLP was molecularly dispersed within the solid nano-system without any signs of interactions. CLP bioavailability in male albino rabbits after oral administration of the optimum CLP-loaded S-SNEDDS formulation compared to the commercially CLP tablets (Plavix®) was investigated. Results revealed that the optimum prepared system exhibited nine folds increment in CLP bioavailability compared to the conventional Plavix® tablets. In conclusion, CLP-loaded S-SNEDDS formulations containing bioenhancing surfactants proved to be a promising approach to improve the oral bioavailability of CLP.