Measurement and mapping of pH in hydrating pharmaceutical pellets using confocal laser scanning microscopy.
OBJECTIVE
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.
Cope
Sandra J
SJ
Institute of Pharmaceutical Sciences Research, School of Pharmaceutical Sciences, University of Nottingham, University Park, United Kingdom.
Hibberd
Stephen
S
Whetstone
Joanne
J
MacRae
Ross J
RJ
Melia
Colin D
CD
D002482:Cellulose / Q000737:chemistry; D004343:Drug Implants / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal / Q000379:methods
D004343:Drug Implants; D002482:Cellulose