A Rheological Approach for Predicting Physical Stability of Amorphous Solid Dispersions.

Miscibility is an important indicator of physical stability against crystallization of amorphous solid dispersions (ASDs). Currently available methods for miscibility determination have both theoretical and practical limitations. Here we report a method of miscibility determination based on the overlap concentration, c*, which can be conveniently determined from the viscosity-composition diagram. The determined c* values for ASDs of two model drugs, celecoxib and loratadine, with four different grades of polyvinylpyrrolidone (PVP), were correlated strongly with the physical stability of ASDs. This result suggests potential application of the c* concept in guiding the design of stable high drug loaded ASD formulations. A procedure is provided to facilitate broader adoption of this methodology. The procedure is easy to apply and widely applicable for thermally stable binary drug/polymer combinations.