Microenvironmental pH control of drug dissolution

Abstract

Microenvironmental pH control has been used to modify the dissolution of pharmaceutical formulations in a predictive manner. An internal buffer system comprising disodium hydrogen orthophosphate and citric acid was incorporated at the 10% w/w level into a frusemide-polyvinylpyrrolidone (PVP) solid dispersion system which was X-ray amorphous, or non-crystalline, in nature. The dissolution rate, determined from constant surface area discs, was shown to be dependent on the phosphate/citric acid ratio of the internal buffer system. The approach proved successful for increasing the dissolution rate of a weakly acidic model drug in acidic media and retarding the dissolution rate in alkaline media. In an attempt to measure the pH at the “surface” of a dissolving compact a technique was developed that utilised a modified dissolution apparatus and a micro-pH probe. The data confirmed that the internal buffer system produced controlled changes in the measured surface pH. The surface pH-dissolution profiles for a series of internally buffered solid dispersions in two dissolution media (0.01 M sodium acetate and 0.01 M acetic acid) displayed a similar pattern to the pH-dissolution profile of an unbuffered X-ray amorphous frusemide-PVP solid dispersion in buffered dissolution media. This approach is proposed to be a useful method for producing controlled changes in the dissolution behaviour of pharmaceutical formulations and may be also applied to the prevention of crystallisation of drugs at the solid/liquid interface.