Development of dexibuprofen loaded nano transfersomal gel with enhanced biopharmaceutical performance in complete Freund's adjuvant induced arthritis model

Abstract

The purpose of this study was to enhance the biopharmaceutical performance of Dexibuprofen (DXI) using transfersomal gel (DXI-TG) as drug delivery system. DXI loaded transfersomes (DXI-T) were prepared via thin film technique, characterized for particle size, polydispersity index, zeta potential, particle morphology and entrapment efficiency. The DXI-T was further incorporated into 2 % (w/v) chitosan gel to get the final dosage form DXI-TG, which was characterized for homogeneity, pH, spread-ability and rheological properties. In vitro release, ex vivo permeation and in vivo studies were also conducted along with stability study of the optimized formulation. DXI-T showed excellent vesicle properties including, size distribution (235.1 ± 4.66 nm), poly dispersity index (0.184 ± 0.001), zeta potential (−10.5 ± 0.23 mV) and entrapment efficiency (82.9 ± 1.07 %). TEM analysis exhibited spherical morphology and uniformly distributed nanoparticles, whereas FTIR showed no bond anomalies. DXI-TG showed suitable gel properties with a viscosity of 11310 ± 20 cP, pH 5.2 ± 0.3, good homogeneity, non-Newtonian flow behavior, good spread-ability (298 ± 7.63 %) and high drug content (97.01 ± 3.1 %). in vitro release studies demonstrated that DXI-TG has significantly controlled the release of DXI when compared with DXI-T, DXI-G and DXI-Suspension at pH 5.5 and 7.4. Similarly, ex vivo permeation analysis showed meaningfully increased permeation of DXI-T followed by DXI-TG when compared with test formulations. Like normal control group, skin irritation studies showed no erythema and edema in DXI-TG treated group. Additionally, DXI-TG demonstrated a significantly enhanced bioavailability (5-fold) when compared with DXI-Suspension and DXI-G. Furthermore, DXI-TG showed significantly enhanced therapeutic effect against acute arthritis model when compared with DXI-Suspension and DXI-G. Besides, no signs of evident toxicity on major body organs was observed in DXI-TG treated animal group. Also, the DXI-TG was found stable for a period of 6 months. It can be concluded that transfersomal gel may be a suitable carrier for DXI with enhanced bioavailability, improved therapeutic efficacy and no evident toxicity as exhibited in this study.