Impact of method of preparation of Amorphous Solid Dispersions on Mechanical Properties: Comparison of co-precipitation and spray drying

Usage of the amorphous phase of compounds has become the method of choice to overcome oral bioavailability problems related to poor solubility. Due to the unstable nature of glasses, it is clear that the method preparation of the amorphous glass will have an impact on physical/chemical stability and in turn in vivo performance. The method of preparation can also have a profound impact on the mechanical properties of the amorphous phase. We have explored the impact of preparation method on the mechanical properties of an amorphous solid dispersion using a development compound, GDC-0810. Three methods were used to generate amorphous solid dispersions (ASD) of 50% GDC-0810 with HPMC-as: (i) Spray drying (SDD), (ii) Co-precipitation using overhead mixing (OHM), and (iii) Co-precipitation using resonant acoustic mixing (RAM). All three methods were found to generate ASDs with good phase mixing and similar glass transition temperatures. Coprecipitated ASD powders (OHM and RAM) demonstrated superior tabletability and flow properties when compared to the SDD powder. Careful choice of manufacturing process can be used to tune material properties of ASDs to make them more amenable for downstream operations like tableting. Acoustic mixing has been demonstrated as a scalable new method to make ASDs through co-precipitation.

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