DESIGN AND PHARMACOKINETIC EVALUATION OF IBRUTINIB BY SELF-NANO-EMULSIFYING DRUG DELIVERY SYSTEM

The objective of present research work is design and in-vivo evaluation of ibrutinib self-nanoemulsifying drug delivery system (SNEDDS) for the enhancement of oral bioavailability. Box-Behnken design was used for the study and the results analysed using response surface methodology. Ibrutinib SNEDDS were prepared with various oils, surfactants and co-surfactants and tested particle size, PDI, zeta potential, refractive index, drug release and TEM studies. The optimized ibrutinib SNEDDS has the composition of capryol 90, cremophore EL and transcutol HP. Based on the particle size and entrapment efficiency and in-vitro dissolution studies; F2 is identified as optimized formulation with 85% drug released, whereas less than 1% was released from pure drug at end time of 30 min. In-vivo bioavailability data reported in male wistar rats indicate higher concentration of drug in plasma implying enhanced systemic absorption of ibrutinib from SNEDDS formulation. The C_max and AUC_0-inf values of optimized SNEDDS was considerably higher (p<0.05) than pure drug formulation. The oral bioavailability of optimized SNEDDS increased around 12 folds when compared with pure drug. Ibrutinib SNEDDS was successfully prepared, and results indicate that oral bioavailability of ibrutinib optimized SNEDDS was significantly improved when compared with pure drug. Therefore, the results suggest that the optimized formulation has a great potential for clinical application in the effective management of lymphocytic leukaemia.