Overcoming challenges for development of amorphous powders for inhalation

Amorphous powder formulations exist in marketed dry-powder inhaler (DPI) products and they will continue to increase. However, amorphous powders are inherently unstable and prone to recrystallize with the aerosol performance reduced if not handled properly.In this review, we described the occurrence of amorphous materials for inhalation resulting from the production process along with major issues and challenges, followed by risk mitigation strategies for amorphous inhalation powders, including protective packaging, processes for minimization of amorphous contents, use of substances with a high glass transition temperature, coating or surface treatment of the powders and co-formulations of drugs. Specific examples were included for illustration of these strategies, and in particular, emphasis was placed on the use of hydrophobic excipients such as leucine and stearates, and co-amorphous glass systems of two drugs or a drug and an excipient.Researchers have been striving to overcome many problems associated with developing and delivering amorphous powders for inhalation. A combination of two or more de-risking approaches covered in this review may help circumvent instability of amorphous inhalation powders and maintain aerosol performance during drug delivery and storage.