The Effect of Azelaic Acid and Vitamin C on the Stability of Hydroquinone in Extemporaneous Topical Preparations: an Evidence-Based In Vitro Research

Abstract

Research has shown that co-administration of preparations containing HQ and azelaic acid (AZ) or vitamin C (vit C) may be more effective than HQ alone. The aim of this study was to evaluate the stability of HQ in the presence of AZ and vit C as active ingredients in the extemporaneous preparations prepared with different techniques. Topical preparations containing HQ, vit C, and AZ were prepared using with aqueous and none-aqueous extemporaneous techniques. Some auxiliary antioxidants were used to stabilize vit C. Thermal stress condition was applied for stability evaluation. Digital images and HPLC analysis were performed to control the color changes and drug loss, respectively. Severe color changes happened in some formulations and dark brown color appeared. Color change was directly attributed to vit C loss but not related to HQ loss. HQ ointment with no antioxidant, showed no loss after stress incubation. AZ was partially able to increase the HQ and vit C stability in a combination formulation, but this stabilizing effect in binary formulations of HQ and AZ was not seen. SMB enhanced vit C stability. Aqueous preparation methods decreased the stability of formulations significantly. It can be recommended that HQ, vit C, and AZ be formulated in separate dosage forms. Avoiding water incorporating or aqueous methods will enhance the stability of these formulations, as well. Intrinsic low stability of vit C in topical formulations may be enhanced using non-water incorporating or non-aqueous methods and utilizing SMB in suitable concentrations.