A computer-based technique was applied for the optimization of recently described multicomponent protective liposomal formulations. These formulations contain riboflavin in either free form or complexed with gamma-cyclodextrin as a model drug, sensitive to photochemical degradation, as well as various light absorbers and antioxidants incorporated into the lipid bilayer and/or the aqueous phase of liposomes. During the liposomal preparation, a series of 11 factors were isolated as important to affect their effectiveness as stabilization systems. These factors were related, first, to the composition of liposomes and, second, to variations during the preparation procedure. The Plackett--Burnam design described in this study was applied for the isolation of the significant factors in order to concentrate more on them. The stabilization ratio of the vitamin was the response variable of the system to be optimized. In order to assure the presence of the examined components in liposomes, the entrapment values were calculated for all the materials, either spectrophotometrically or using second-order derivative spectrophotometry. The optimum formulation should be characterized from the higher protection of the drug.