2(k–p) Fractional Factorial Design via Fold Over: Application to Optimization of Novel Multicomponent Vesicular Systems
Abstract
A computer-based technique based on a 2(k–p) fractional factorial design was applied for the optimization of recently described multicomponent protective liposomal formulations. These formulations contain riboflavin (vitamin B2) as a model, photosensitive drug, in addition to Oil Red O, deoxybenzone, oxybenzone and β-carotene as oil-soluble light absorbers and antioxidants incorporated into the lipid bilayer, and sulisobenzone as a water-soluble light absorber incorporated into the aqueous phase of liposomes. The presence or absence of these five different light absorbers in multilamellar liposomes containing the vitamin free or complexed with γ-cyclodextrin comprised the six factors of the system, each one examined at two levels. The stabilization ratio of the vitamin and its percentage entrapment in liposomes were the two response variables of the system to be optimized. The entrapment values were calculated for all the materials, either spectrophotometrically, using second-order derivative spectrophotometry, or fluorimetrically. The response variables were predicted by multiple regression equations comprising combinations of the six formulation factors. Higher entrapment and higher protection for the drug should characterize the optimum formulation.