Effect of pH in the structure and mass transport by diffusion of theophylline

Highlights: • Ternary mutual diffusion coefficients of aqueous theophylline plus HCl solutions. • Ternary mutual diffusion coefficients of aqueous theophylline plus NaOH solutions. • Coupled diffusion as indicated by cross-diffusion coefficients. - Abstract: The influence of hydrochloric acid and sodium hydroxide on the diffusion of aqueous solutions of theophylline (TPh) has been investigated by using Taylor dispersion method to measure ternary mutual diffusion coefficients for aqueous solutions of (TPh + HCl) and (TPh + NaOH) at 25 °C. The goal of this research is to have an assessment on the effect of the pH on the transport of this drug and thus giving a better understanding on the mechanisms behind the mass transport by diffusion. This has been complemented with ¹H and ¹³C NMR spectroscopy combined with DFT calculations allowing to confirm the presence of different species depending on the local pH, corresponding to the doubly protonated TPh (pH 2.0), singly protonated TPh (pH 3.0), and the neutral TPh base, above pH 8.8.