How can you produce amorphous drug particles?

Answer 1

There are many possibilities to create amorphous drug particles. Precipitation from an organic or aqueous solution is the most frequently used route. However, the precipitation has to be fast enough to avoid conversion into thermodynamically more stable crystalline states. Liquid antisolvent techniques, spray drying or supercritical fluid techniques can be used to generate amorphous solid drug particles. However, for a large number of drugs the amorphous state is highly unstable and usually precipitation is performed together with a polymer. The polymer is usually amorphous and acts as a matrix preventing the recrystallization of the drug. The choice of polymer depends if a fast, or immediate release or a slow, controlled release form is desired. However, the polymer choice can limit the applicability of certain production techniques due to its solubilty profile in solvents, its potential immiscibility with the drug and or the solvent. Only if all these parameters are considered can a physically stable amorphous form be created successfully. Additionally it should be noted that amorphous drug particles tend to show increased chemical degradation with time in comparison to crystalline forms. It is a separate challenge to also ensure chemical stability of an amorphous drug through addition of suitable excipients. However, as in the case of the polymer addition the necessary excipients might further limit the choice of available processes.