2((K-P)) FRACTIONAL FACTORIAL DESIGN VIA FOLD OVER - APPLICATION TO OPTIMIZATION OF NOVEL MULTICOMPONENT VESICULAR SYSTEMS

A computer-based technique based on a 2((k-p)) fractional factorial de sign was applied for the optimization of recently described multicompo nent protective liposomal formulations, These formulations contain rib oflavin (vitamin B-2) as a model, photosensitive drug, in addition to Oil Red O, deoxybenzone, oxybenzone and beta-carotene as oil-soluble l ight absorbers and antioxidants incorporated into the lipid bilayer, a nd sulisobenzone as a mater-soluble light absorber incorporated into t he aqueous phase of liposomes, The presence or absence of these five d ifferent light absorbers in multilamellar liposomes containing the vit amin free or complexed with gamma-cyclodextrin comprised the six facto rs of the system, each one examined at two levels, The stabilization r atio of the vitamin and its percentage entrapment in liposomes were th e two response variables of the system to be optimized, The entrapment values were calculated for all the materials, either spectrophotometr ically, using second-order derivative spectrophotometry, or fluorimetr ically. The response variables were predicted by multiple regression e quations comprising combinations of the six formulation factors, Highe r entrapment and higher protection for the drug should characterize th e optimum formulation.