Box Behnken design

  The present research work aimed at development and optimization of niosome based gel (NBG) for the vaginal delivery of Tenofovir disoproxil fumarate (TDF). The TDF was   incorporated into niosomes using span 60 and cholesterol. Box-Behnken statistical screening design with 3 factors, 3 levels, and 15 runs was selected to statistically optimize the formulation parameters. The independent variables selected were parts of cholesterol (X1), surfactant loading (X2), amount of stabilizer (X3). Fifteen batches were prepared by thin film hydration method and evaluated for percentage drug entrapment (PDE) and vesicle size. The transformed values of the independent variables and the PDE (dependent variable) were subjected to multiple regressions to establish a full-model second-order polynomial equation. F value was calculated to confirm the omission of insignificant terms from the full-model equation to derive a reduced-model polynomial equation to predict the PDE of niosome. A model was validated for accurate prediction of the PDE by performing checkpoint analysis. The niosomal dispersion was incorporated in to Carbopol 940NF gel. The NGB was evaluated for drug content, pH, spreadability, consistency and texture analysis. The in-vitro drug release study shows sustained release gel effect whereas the in-vivo study shows no signs of irritation on the applied vaginal site in rat. The gel was kept for 6 weeks accelerated stability studies. The niosomes and niosomal gel showed maximum stability at 2 to 8 °C.   Key-words: Niosome, vaginal drug delivery, Tenofovir disoproxil fumarate, span 60, Box Behnken design