Successful oral delivery of fexofenadine hydrochloride by improving permeability via phospholipid complexation

The present work aimed to enhance liposolubility along with intestinal permeability of BCS class III drug fexofenadine (FEX) via phospholipid complexation strategy in order to improve its oral bioavailability. This work demonstrated the minimized P-gp efflux and augmented absorption of FEX when fabricated as phospholipid complex. The fexofenadine-phospholipid complex (FEX-PLC) was prepared using widely used solvent evaporation method. Among three phospholipids, Phospholipon® 90 H was screened out for further studies due to high drug content and physical form. The FTIR spectra demonstrated the disappearance of characteristic peaks of FEX which could be attributed to shielding by phospholipid due to molecular interactions between FEX and phospholipid. The differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) revealed the amorphous state of FEX in the complex. The partition coefficient study indicated the increased in lipophilicity which can further be correlated with 1.85 ± 0.850 fold enhancement in intestinal permeability of FEX-PLC in comparison to FEX in Caco-2 permeability assay. Furthermore, efflux ratio of FEX was decreased significantly from 4.04 (FEX) to 1.34 (FEX-PLC) which indicated inhibition of P-gp efflux of FEX. The in vivo evaluation in Wistar rats presented 3.38 fold increment in oral bioavailability of FEX-PLC as compared to FEX. In summary, the phospholipid complexation demonstrated as a simple and promising approach to tackle oral bioavailability hurdles of BCS class III drugs and convert them to BCS class I drugs. © 2020 Elsevier B.V.