A COMPUTER-BASED EXPERT-SYSTEM DESIGNS AND ANALYZES A 2((K-P)) FRACTIONAL FACTORIAL DESIGN FOR THE FORMULATION OPTIMIZATION OF NOVEL MULTICOMPONENT LIPOSOMES

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 sod ium ascorbate (vitamin C) as a model drug sensitive to photochemical o xidation, 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 l iposomes. The three light absorbers (present or absent) incorporated i n multilamellar liposomes and the drug in free or in complexed with al pha-cyclodextrin form comprised the four factors of the system. The st abilization ratio and the percentage entrapment in the liposomes of th e vitamin were the two response variables of the system to be optimize d. The entrapment values were calculated for all the materials either spectrophotometrically or by using second order derivative spectrophot ometry. The response variables were predicted by multiple regression e quations comprising combinations of the four formulation factors. Both the higher entrapment and the higher protection for the drug should c haracterize the optimum formulation. (C) 1998 Elsevier Science B.V. Al l rights reserved.