Considerations for the selection of co-formers in the preparation of co-amorphous formulations

Co-amorphous drug delivery systems are evolving as a credible alternative to amorphous solid dispersions technology. In Co-amorphous systems (CAMs), a drug is stabilized in amorphous form using small molecular weight compounds called as co-formers. A wide variety of small molecular weight co-formers have been leveraged in the preparation of CAMs. The stability and supersaturation potential of prepared co-amorphous phases largely depend on the type of co-former employed in the CAMs. However, the rationality behind the co-former selection in co-amorphous systems is poorly understood and scarcely compiled in the literature. There are various facets to the rational selection of co-former for CAMs. In this context, the present review compiles various factors affecting the co-former selection. The factors have been broadly classified under Thermodynamic, Kinetic and Pharmacokinetic-Pharmacologically relevant parameters. In particular, the importance of Glass transition, Miscibility, Liquid-Liquid phase separation (LLPS), Crystallization inhibition has been deliberated in detail.