Formulation optimization of novel multicomponent photoprotective liposomes by using response surface methodology

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Abstract
A computer optimization technique based on response surface methodology has been applied for the optimization of recently described multicomponent photoprotective liposomal formulations. These formulations contain riboflavin as a model photosensitive drug as well as oil red O as an oil-soluble light absorber incorporated into the lipid bilayer, and sulisobenzone as a water-soluble light absorber incorporated into the aqueous phase of liposomes. The presence of these two different light absorbers and the molar ratio between the liposome components, egg phosphatidylcholine and cholesterol, comprise the three factors of the system; each one has been examined in three levels. The percentage entrapment of the photosensitive riboflavin and its photodegradation rate constant were the two response variables of the system to be optimized. The entrapment values were calculated for all the materials, either spectrofluorimetrically or by using second-order derivative spectrophotometry. The photodegradation rate constant was calculated spectrofluorimetrically. The response variables were predicted by multiple regression equations comprising combinations of the three formulation factors. The regression equations for the two response variables were examined as a simultaneous optimization problem and predicted response values were successfully validated. The optimum formulation should be characterized from both the higher entrapment and the higher photoprotection for the drug.

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