The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems

Many pharmaceuticals, either by accident or design, may exist in a total or partially amorphous state. Consequently, it is essential to have an unders tanding of the physico-chemical principles underpinning the behaviour of su ch systems. In this discussion, the nature of the glassy state will be desc ribed, with particular emphasis on the molecular processes associated with glass transitional behaviour and the use of thermal methods for characteris ing the glass transition temperature, T-g. The practicalities of such measu rements, the significance of the accompanying relaxation endotherm and plas ticization effects are considered. The advantages and difficulties associat ed with the use of amorphous drugs will be outlined, with discussion given regarding the problems associated with physical and chemical stability. Fin ally, the principles of freeze drying will be described, including discussi on of the relevance of glass transitional behaviour to product stability. ( C) 1999 Published by Elsevier Science B.V. All rights reserved.