CONSTRUCTION OF A DIFLUNISAL ION SENSOR AND ITS USE IN AUTOMATED FLOW-INJECTION METHODS FOR ASSAY, CONTENT UNIFORMITY, AND DISSOLUTION STUDIES OF FORMULATIONS

A diflunisal ion selective electrode of the PVC membrane type with an ion-exchanger consisting of the tetraheptylammonium-diflunisal ion pai r is described. The sensor exhibits a rapid, near-Nernstian, selective response to diflunisal anion in the pH range 7-10, with a (batch) det ection limit of 1 x 10(-5) M. The ion sensor was used as a flow detect or in an automated flow-injection analyzer to develop routine methods for assays (concentration range 1-50 x 10(-4) M, (flow) detection limi t 2.6 x 10(-5) M), content uniformity, and dissolution studies of difl unisal formulations. No serious interference from common ions and tabl et excipients was found, and the drug can be directly determined in co lored samples without separation steps. Fourty measurements can be per formed automatically per hour with a precision of 0.5-1.8% relative st andard deviation. The automated method for the dissolution test provid es a complete dissolution profile by the end of the experiment. Using the constructed ion sensor, the intramolecular hydrogen bonding of the diflunisal anion was studied, thereby revealing a new application of ion sensor potentiometry.