Effect of reactive and non-reactive counterion micelles upon the alkaline degradation of indomethacin

In the present paper, kinetics of alkaline degradation of well known drug, indomethacin (2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid), was studied in presence of excess [NaOH]. The rate of hydrolysis of substrate was independent of the [indomethacin] though it increased linearly with increasing the hydroxide ion concentration with a positive slope, suggesting the following rate law: kobs = k1[OH−]. Cationic surfactants having non-reactive ions (cetyltrimethylammonium bromide, CTAB and cetyltrimethylammonium sulfate (CTA)2SO4) first increased the rate constants at lower concentrations and then decreased it at higher concentrations while in case of the surfactant with reactive counterions (cetyltrimethylammonium hydroxide, CTAOH) the rate increases sharply at lower concentrations of surfactant until it reaches to a plateau in contrast to the appearance of maxima in case of CTAB and (CTA)2SO4. Anionic surfactant, sodium dodecyl sulfate (SDS), inhibited the reaction rate at all concentrations used in the study. Pseudophase ion-exchange model was used for analyzing the effect of cationic micelles while the inhibition by SDS micelles was fitted using the Menger–Portnoy model. The effect of salts (NaCl, NaBr and (CH3)4NBr) was also seen on the hydrolysis of indomethacin and it was found that all salts inhibited the rate of reaction. The inhibition followed the trend NaCl < NaBr < (CH3)4NBr.

The rate of alkaline hydrolysis of indomethacin shows the maxima as the concentration of cationic surfactants, CTAB and (CTA)2SO4 increase. In contrast the rate increases in presence of CTAOH until it reaches a plateau at higher [surfactant].Figure optionsDownload as PowerPoint slide