Rofida Albash, Abdurrahman M. Fahmy, Maha H. Ragaie, S. Sohail Ahmed, Rabab A. El-Gazar, Amira B. Kassem, Manar Adel Abdelbari, Hoda A. Salem, Asmaa Saleh, Shaimaa Mosallam
Background/Objectives: Aspasomes (ASPs) are composed of ascorbyl palmitate (AP), which has antioxidant activity. The objective of this study was the formulation of aspasomes (ASPs) loaded with metformin hydrochloride (MFC) for the topical treatment of melasma. Methods: MFC-ASPs were prepared using the thin-film method with different amounts of phospholipid and ascorbyl palmitate (AP) in the absence or presence of ethanol surfactant. The prepared formulations were optimized using a D-optimal mixture. The assessed responses included entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Results: The optimum OASPs, composed of 193.121 mg PC and 30 mg AP, exhibited spherical vesicles with an EE% of 87.50 ± 0.33%, PS of 264.47 ± 0.02 nm, PDI of 0.423 ± 0.001, and ZP of −21.67 ± 0.12 mV. The optimum formula represented a spherical morphology using transmission electron microscopy, along with sustained release behavior compared with MFC. Also, it showed good stability for up to 90 days. Furthermore, a clinical appraisal of patients with melasma confirmed the superiority of the cream compared to the other cream in clinical study. Conclusions: The optimum OASPs present a promising approach for the treatment of melasma topically.