Comparative Stability of Two Anti-Hyperpigmentation Agents: Kojic Acid as a Natural Metabolite and Its Di-Palmitate Ester, Under Oxidative Stress; Application to Pharmaceutical Formulation Design

Kojic acid a natural metabolite (KA) and its dipalmitate ester, kojic acid dipalmitate (Kadp) are both prescribed to treat skin hyperpigmentation. Stress test reveals the intrinsic stability of active ingredients and leads to selection of the suitable formulations. This research evaluates the comparative stability of KA and its di-palmitate ester under liquid oxidative stress.

The HPLC-UV/PDA method with a C18 column was utilized. Liquid oxidative stress was induced using hydrogen peroxide (H2O2). Degradation was separately induced for each drug, and they were compared to each other.

Kadp degraded more rapidly in similar liquid oxidative stress conditions than KA did. The superior degradation model was the first order for both drugs based on the MPE values, indicating the dependency of the reaction rate on the initial concentration of the reactive substance. Ring opening was proposed as the most possible theory for KA and Kadp oxidative degradation.

It is suggested to use KA instead of Kadp in less stable formulations, such as extemporaneous preparations. The incorporation of antioxidant excipients in Kadp formulations is recommended for yielding better stability results. Formulating Kadp in the internal phase of o/w emulsion formulations may protect this susceptive molecule from oxidative degradation during the shelf life of the pharmaceutical preparation. Further studies are required to study the exact mechanism of the degradation process.