Development of a perillyl alcohol topical cream formulation.

Perillyl alcohol (POH) is a relatively non-toxic agent that has been shown to be a promising anticancer monoterpene in preclinical models. Studies have indicated that topical application of POH may prove to be effective as a skin cancer chemoprevention therapy. The main aim of this study was to determine the influence of several factors on the stability of POH in solution and develop a topical formulation of POH. During preformulation, the influence of pH, temperature, ionic strength, and organic solvents, on the stability of POH was evaluated at four different temperatures: 4, 25, 37, and 48 degrees C. POH was found to degrade under acidic conditions with degradation following apparent first-order kinetics. A hydrophilic topical cream formulation of POH was developed and prepared for toxicology and clinical studies. A reverse phase gradient HPLC method was developed to quantitate POH in the complex formulation. Stability studies of the formulation and a placebo were performed and the formulation was found to be physically and chemically stable over a period of 1 year at 4 and 25 degrees C.