1452 ORAL The multitargeted kinase inhibitor sunitinib malate (SU11248): soluble protein biomarkers of pharmacodynamic activity in patients with metastatic renal cell cancer

Abstract

Simvastatin (SIM) and glimepiride (GLM) were co-formulated into nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) to improve their dissolution rate and oral bioavailability. Nanosuspension was prepared by liquid anti-solvent precipitation method, involving supersaturation of a solution by mixing the drug solution in an antisolvent. Liquid SNEDDS were prepared by loading drugs into an isotropic mixture of Capmul MCM, Labrafil M1944CS, Tween-80 and Transcutol P. Both formulations were solidified using spray drying. Enhancement in dissolution rate by 6.4 folds and 4.45 folds was observed for GLM and SIM respectively by preparing their nano-formulations. Drugs’ permeability was also enhanced by loading them into nano-formulations. The pharmacokinetic studies were conducted on rats which revealed increase in oral bioavailability by 6.69- and 4.22-folds for GLM and 1.76- and 2.68-folds for SIM respectively for nanosuspension and solid SNEDDS than their unprocessed forms. Both dissolution rate and oral bioavailability of SIM and GLM got significantly improved through S-SNEDDS and nanosuspension. However, performance of nanosuspension was found better than SNEDDS in terms of dissolution rate and oral bioavailability.