Photolysis of tolfenamic acid in aqueous and organic solvents: a kinetic study

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug that was studied for its photodegradation in aqueous (pH 2.0-12.0) and organic solvents (acetonitrile, methanol, ethanol, 1-propanol, 1-butanol). TA follows first-order kinetics for its photodegradation, and the apparent first-order rate constants (k _obs) are in the range of 0.65 (pH 12.0) to 6.94 × 10^-2 (pH 3.0) min^-1 in aqueous solution and 3.28 (1-butanol) to 7.69 × 10^-4 (acetonitrile) min^-1 in organic solvents. The rate-pH profile for TA photodegradation is an inverted V (∧) or V-top shape, indicating that the cationic form is more susceptible to acid hydrolysis than the anionic form of TA, which is less susceptible to alkaline hydrolysis. The fluorescence behavior of TA also exhibits a V-top-shaped curve, indicating maximum fluorescence intensity at pH 3.0. TA is highly stable at a pH range of 5.0-7.0, making it suitable for formulation development. In organic solvents, the photodegradation rate of TA increases with the solvent's dielectric constant and solvent acceptor number, indicating solute-solvent interactions. The values of k _obs decreased with increased viscosity of the solvents due to diffusion-controlled processes. The correlation between k _obs versus ionization potential and solvent density has also been established. A total of 17 photoproducts have been identified through LC-MS, of which nine have been reported for the first time. It has been confirmed through electron spin resonance (ESR) spectrometry that the excited singlet state of TA is converted into an excited triplet state through intersystem crossing, which results in an increased rate of photodegradation in acetonitrile.