Purpose: pH modifiers are often used to promote drug solubility/ stability in dosage forms, but predicting the extent and duration of internal pH modification is difficult. Here, a noninvasive technique is developed for the spatial and temporal mapping of pH in a hydrated pharmaceutical pellet, within a pH range appropriate for microenvironmental pH control by weak acids.
Methods: Confocal dual excitation imaging (Ex 488/Ex 568) of pellets containing a single, soluble, pH-sensitive fluorophore with cross-validation from a pH microelectrode. The technique was used to investigate the changing pH distribution in hydrating pellets containing two weak acids of differing solubility.
Results: The algorithm developed provided pH measurements over the range pH 3.5-5.5 with a typical accuracy of 0.1 pH units and with excellent correlation with pH microelectrode measurements. The method showed how pellets containing 25%w/w tartaric acid exhibited a rapid but transient fall in internal pH, in contrast to a slower more prolonged reduction with fumaric acid.
Conclusions: Spatial and temporal monitoring of pH in pellets was achieved with good accuracy within a pH range appropriate to pH modification by weak acids. However, the method developed is also generic and with suitable fluorophores will be applicable to other pH ranges and other dosage forms.