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

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 (R) 300 to produce S-SNEDDS. Results showed that SNEDDS-8 (SII8) consisting of 10% Capryol (TM) 90, 10% Cremophore (R) EL and 80% Transcutol (R) 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 (R)) was investigated. Results revealed that the optimum prepared system exhibited nine folds increment in CLP bioavailability compared to the conventional Plavix (R) tablets. In conclusion, CLP-loaded S-SNEDDS formulations containing bioenhancing surfactants proved to be a promising approach to improve the oral bioavailability of CLP.