This study investigated the interfacial behaviors of non-ionic surfactants at the air-liquid and solid-liquid interfaces including the work of adhesion derived from surface tension and contact angle measurements and explored their potential link to the physical stability of pharmaceutical suspensions. Surface tension measurements using pendant drop tensiometry revealed varying capacities of seven non-ionic surfactants to reduce the surface tension of water, with polysorbate 20 achieving the lowest equilibrium surface tension (36.07 ± 1.08 mN/m) and poloxamer 188 the highest (48.89 ± 0.20 mN/m). Contact angle measurements were performed between 0.5 mM, 1 mM, and 2 mM surfactant solutions and thin spin-coated drug films of eight model compounds to assess solid-liquid wettability and calculate the work of adhesion. All surfactant solutions exhibited contact angles below 90°, suggesting favorable spreading on drug compound surfaces, though compound-specific differences in wettability were observed. Some surfactant-drug compound combinations, such as polysorbate 20 with naproxen or TBAJ-876, showed contact angles near 0°, potentially indicating superspreading behavior. The work of adhesion, derived from surface tension and contact angles, generally decreased in the presence of surfactants compared to water, and slightly increased with higher surfactant concentration. Pharmaceutical suspensions with the eight model drug compounds were evaluated for physical stability, assessed by monitoring the particle size profiles for 28 days at 40 °C to assess stabilization efficiency to maintain the sizes of drug particles during storage. While some correlations between low work of adhesion and poor stabilizer performance were noted - such as vitamin E TPGS with bedaquiline and poloxamer 188 with haloperidol - no consistent trend was observed across all surfactants and drug compounds. Most data clustered closely, with outliers offering limited predictive value between interfacial measurements and particle size profiles. These findings therefore suggested that although interfacial energy measurements provided valuable insight into surfactant behavior and solid-liquid interactions, they were not sufficient as standalone predictors of physical stability in pharmaceutical suspensions.
Zulbeari et al. (Tue,) studied this question.