• Prof. (Dr.) Dinesh Kumar Mishra
• Krishna Kant Jangde
• Kashinath Mahato
• Dr. Anuja Mishra
• Animesh Mishra , Pratibha Nair

Conventional management of localized pain relies heavily on systemic therapeutics, which carry substantial gastrointestinal and systemic risks. Topical polyherbal systems offer a high-compliance alternative but frequently lack structural optimization and mechanistic validation. This study engineered, physically optimized, and computationally validated a natural polyherbal roll-on balm containing essential oils of peppermint, eucalyptus, clove, rosemary, and camphor designed for synergistic multi-target pain and inflammation management. Four lipid-based formulations (F1–F4) were fabricated via controlled thermomechanical blending. High-resolution molecular docking elucidated the thermodynamic binding landscapes of principal phytoconstituents against core nociceptive and inflammatory targets, including COX-1/2, 5-LOX, TRPM8, TRPV1, and TRPA1. Optimized formulation F1 and F3 demonstrated exceptional optical clarity, structural homogeneity, and robust physical stability under accelerated stress. The matrices precisely matched skin physiological pH (4.7–5.0), inducing zero dermal irritation or microbial bioburden while exhibiting a distinct biphasic warming-to-cooling sensory profile. Computational profiling successfully rationalized this synergy: eugenol exhibited highly potent binding affinity within the catalytic pocket of COX-2 (-6.9 kcal/mol), while menthol anchored robustly to the cold-sensing TRPM8 receptor via targeted Arg842 hydrogen bonding (-6.7 kcal/mol), providing a definitive structural rationale for the balm's multi-pathway analgesia.

Topical Drug Delivery; Polyherbal biomatrix; Multi-target Analgesia; Molecular docking; Thermodynamic stability; Essential oils.

"Formulation Development, Physicochemical Evaluation, and in silico Analysis of a Polyherbal Roll-on Balm for Pain Management", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.13, Issue 9, page no.b584-b591, September-2026, Available :http://www.jetir.org/papers/JETIR2609165.pdf

"Formulation Development, Physicochemical Evaluation, and in silico Analysis of a Polyherbal Roll-on Balm for Pain Management", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.13, Issue 9, page no. ppb584-b591, September-2026, Available at : http://www.jetir.org/papers/JETIR2609165.pdf