Integrated Evaluation of Radiosterilization Suitability in Topical Antimycotics Using a Physicochemical Hybrid Approach

This study presents an integrated physicochemical approach for evaluating the gamma-radiation stability of selected topical antimycotic agents, combining Monte Carlo N-Particle eXtended (MCNPX)–based radiophysical simulations with forced degradation profiling via (RPLC). Climbazole, Oxiconazole, and Sertaconazole were assessed using MCNPX (v2.7.0) to model photon-matter interactions across a broad energy range (0.015 to 15 MeV), generating key radiophysical metrics, including the mass attenuation coefficient, half-value layer, effective atomic number, kerma, dose rate, energy absorption buildup factors, and the specific absorbed fraction of energy. Simultaneously, each compound underwent stress-induced degradation under acidic, basic, oxidative, photolytic, and thermal conditions, with RPLC analysis performed using a Pinnacle DB Cyano column and ultraviolet detection at 202 nm. First-order degradation kinetics (rate constant k and half-life t1/2) were calculated to assess chemical resilience. The integration of radiophysical and chemical stability data revealed compound-specific vulnerability profiles: sertaconazole demonstrated superior gamma attenuation and oxidative-photolytic stability, while climbazole exhibited lower shielding efficiency but retained kinetic resistance under thermal stress. To the best of our knowledge, this is the first study to implement a dual-modality methodology linking MCNPX-based photon transport modeling with experimentally validated degradation kinetics to predict radiosterilization suitability in pharmaceutical compounds. This hybrid model offers a robust decision-making framework for optimizing sterilization strategies, and may be extrapolated to broader pharmaceutical classes, including injectables and biopharmaceuticals.