A computer-based expert system designs and analyzes a 2 ( k− p) fractional factorial design for the formulation optimization of novel multicomponent liposomes

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 sodium ascorbate (vitamin C) as a model drug sensitive to photochemical oxidation, as well as oil red O and/or oxybenzone as oil soluble light absorbers, incorporated into the lipid bilayers and sulisobenzone as a water soluble light absorber incorporated into the aqueous phase of liposomes. The three light absorbers (present or absent) incorporated in multilamellar liposomes and the drug in free or in complexed with α-cyclodextrin form comprised the four factors of the system. The stabilization ratio and the percentage entrapment in the liposomes of the vitamin were the two response variables of the system to be optimized. The entrapment values were calculated for all the materials either spectrophotometrically or by using second order derivative spectrophotometry. The response variables were predicted by multiple regression equations comprising combinations of the four formulation factors. Both the higher entrapment and the higher protection for the drug should characterize the optimum formulation.