PREFORMULATION STUDIES INVOLVING MOISTURE UPTAKE IN SOLID DOSAGE FORMS

The rates of moisture sorption and the resultant effect on stability of a moisture-sensitive drug blended or formulated with different components are addressed. Total moisture increase was determined by weight gain, and change in mobile water level by water activity measurements. Equilibrium relative humidity is a useful tool in predicting the stability of a moisture-sensitive drug in solid dosage forms. Since immobile water is perceived not to react chemically, the amount of mobile water rather than total water is the critical parameter in degradation reactions involving hydrolysis. Materials that have a high capacity for binding water equilibrate more slowly to higher levels of mobile water and consequently show greater chemical compatibility with a moisture-sensitive drug than materials with lower binding capacities for water.