Photophysics-Surface Energy Coupling Predicts Polymer Deposition and Dose Drift in Metered-Dose Inhalers

Metered-dose inhalers (MDIs) can exhibit actuation-dependent dose drift due to progressive deposition of drug material on internal polymeric components, affecting delivered-dose consistency. In this study, we investigated whether molecular photophysical behavior can serve as a mechanistic descriptor of polymer-surface deposition propensity for two model ??-adrenergic agonists, terbutaline and salbutamol. A Deposition Propensity Index (DPI=k_q?((?_f x ?_0)) ) was derived from fluorescence quantum yield (?_f), intrinsic excited-state lifetime (?_0), and bimolecular quenching constant (k_q). DPI values spanned approximately four orders of magnitude ((1016-1020) and increased by approximately three logarithmic units under acidic conditions. A linear correlation (R2 = 0.893) was observed between log??(DPI)? and experimentally determined deposition percentages, yielding the relationship:Deposition (%)=7.34 x log??(DPI)-115.81?. Salbutamol exhibited a higher acidic-condition DPI (log??(DPI)?=20.16) than terbutaline log??(DPI)?=19.78), consistent with its greater cumulative deposition after 200 actuations (33.3% vs 28.0%). Simulated-use studies showed actuation-dependent variability in shot weight and delivered concentration, with platform-dependent differences in dose drift behavior. These findings suggest that photophysical sensitivity may provide a mechanistic screening parameter for formulation?device compatibility. Given the limited dataset, the proposed correlation should be considered a proof-of-concept framework requiring validation across a broader range of drug molecules and inhaler systems.