Distribution of Water in Solid Pharmaceutical Systems

Abstract

Knowledge of the amount of moisture associated with particular components of a solid dosage form, as well as its state, are essential for the pharmaceutical formulator in attaining a system with optimal physical/chemical properties. Moisture is introduced into ultimately closed pharmaceutical systems either associated with the materials or in the headspace as relative humidity. This moisture will distribute (i. e., reequilibrate) between the various components and the headspace to attain a final water activity, aw (-relative humidity/100) in the vapor phase. The Sorption-Desorption Moisture Transfer (SDMT) model allows a priori prediction of this thermodynamic variable for systems in which uptake isotherms and dry masses for individual components, temperature, headspace volume and initial total system moisture content are known. Final component moisture contents are then obtained from the individual materials' respective isotherms. Practical applications of the SDMT model include the rational determination of: initial LOD values of the formulation and capsule to avoid capsule brittleness problems, an adequate headspace volume above nonhydrating crystalline substances to protect against deliquescence, and the appropriate amount of desiccant for a solid product.