Assessing Drug‐Micellar Partitioning Via Semi‐Equilibrium Dialysis and Differential Absorbance: Diclofenac, Diflunisal, and Flurbiprofen in Polysorbate 20

ABSTRACT Surfactant micelles are widely used to improve the aqueous solubility and delivery performance of poorly water‐soluble drugs. For micellar drug‐delivery systems, the extent of drug partitioning between the bulk aqueous phase and the micellar pseudo‐phase is a key determinant of solubility enhancement, drug retention, release behavior, and bioavailability. In this study, the micellar partitioning of three halogenated non‐steroidal anti‐inflammatory drugs (NSAIDs)—diclofenac (DFC), diflunisal (DFL), and flurbiprofen (FLP)—was investigated in nonionic polysorbate 20 (Tween 20; T20) micelles using semi‐equilibrium dialysis (SED) and differential absorbance spectroscopy. Both methodologies demonstrated that micellar partitioning followed the order FLP < DFL < DFC. Values of the solubilization constant, K C , were in the range of 68–360, with K C defined as where is the mole fraction of drug in micelles, is the molar concentration of free drug, and is the standard state concentration (. SED‐derived solubilization isotherms further showed that K C was not strictly constant but increased with increasing mole fraction of NSAID in the micelles, suggesting a synergistic solubilization effect, likely arising from favorable structural changes in the micellar environment as drug loading increases. Importantly, the partition coefficients obtained by differential absorbance were in good agreement with SED‐derived values at comparable micellar compositions, indicating that differential absorbance can provide a rapid and experimentally efficient estimate of NSAID partitioning in suitable surfactant systems.