Importance of Glass Transition Temperature in Accelerated Stability Testing of Amorphous Solids: Case Study Using a Lyophilized Aspirin Formulation

During the development and formulation screening for a lyophilized dosage form, one of the most important characteristic of the amorphous lyophilized solid that is usually not considered is its glass transition temperature. The knowledge of Tg for various formulations becomes especially important during the initial stages of formulation development, when formulation screening is done predominantly by monitoring the stability of various formulations under accelerated conditions (i.e. high temperature and humidity) and extrapolating their stability to the storage temperature. This extrapolation assumes that reaction mechanism does not change with temperature and that the reaction obeys Arrhenius kinetics. 1 Added to the complexity that reaction mechanisms may inherently be temperature dependent, any physical change (e.g. due to glass transition) in the dosage form can further complicate the data interpretation and may render the information from high-temperature studies useless. As a consequence, it is likely that several incorrect decisions may be made during the formulation screening and development.