Enhanced oral bioavailability of Bisdemethoxycurcumin-loaded self-microemulsifying drug delivery system: Formulation design, in vitro and in vivo evaluation

In this study, we sought to overcome the poor solubility and bioavailability of bismethoxycurcumin (BDMC) by fabricating a BDMC-loaded self micro-emulsifying system (BDMC-SMEDDS). Solubility and compatibility tests, pseudo-ternary phase diagrams (PTPDs) as well as d-optimal concept was applied to design the formulation. The assessment of the prepared BDMC-SMEDDS in-vitro mainly included droplet size (DS) and entrapment efficiency (EE) determination, morphology, drug release and stability testing. Besides, the in vivo behavior was also evaluated after oral administration of BDMC-SMEDDS to rats. The optimal formulation was found to compose of Kolliphor EL (K-EL, emulsifier, 645.3 mg), PEG 400 (co-emulsifier, 147.2 mg), ethyl oleate (EO, oil, 207.5 mg) and BDMC (50 mg). The BDMC-SMEDDS with satisfactory stability had a mean size of 21.25 +/- 3.23 nm and EE of 98.31 +/- 0.32%. Roughly 70% of BDMC was released from BDMC-SMEDDS within 84 h compared with <20% from the free BDMC. More importantly, the in-vivo behavior of BDMC-SMEDDS showed that the AUC( 0-12h) and plasma concentration of BDMC increased substantially as compared to the free BDMC. Altogether, BDMCSMEDDS has the potential to enhance the solubility and bioavailability of BDMC and could be applied in the clinics.