Andrographolide and Mahua Oil-Infused Emulgels: A Comprehensive QbD, In Vitro, and In Silico Strategy for Skin Pigmentation Treatment.

Skin pigmentation disorders such as melasma, hyperpigmentation and age spots are primarily associated with excessive melanin production and are a significant dermatological concern. To address this issue, the present study aimed to develop an effective skin-lightening formulation by synergising the therapeutic benefits of andrographolide with the skin permeation-enhancing properties of Mahua oil. A two-factor factorial design was employed to formulate and optimise the emulgel using a quality by design (QbD) approach. The optimised formulation (AG-6) was subjected to a series of evaluations, including preliminary characterisation, biocompatibility analysis, in vivo skin uptake studies and tyrosinase inhibition assays. Biocompatibility assessment revealed a 92.64% viability of human dermal fibroblast (HDF) cells after 24 h of AG-6 treatment, indicating low cytotoxicity. Tyrosinase inhibition was observed at 28.94 µg/mL for AG-6, which is comparable to the reference standard Kojic acid (25.37 µg/mL). Furthermore, molecular docking studies demonstrated that andrographolide exhibited a stronger binding affinity with tyrosinase-related protein 1 (TYR1, PDB ID: 5M8L), with a binding energy of -7.9 kcal/mol, as compared to kojic acid (-5.6 kcal/mol). These findings suggest that the optimised emulgel AG-6 holds significant potential for the management of skin pigmentation disorders.