Overcoming challenges for development of amorphous powders for inhalation

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• Amorphous
• powder formulation
• inhalation
• moisture protection

Article highlights

• Amorphous powders in dry-powder inhalation products contribute to innovative and effective aerosol therapy. However, physical instability of amorphous powders is problematic and the dispersibility of the powder may be compromised upon exposure to surrounding moisture.

• Various powder production processes, such as milling, spray drying, supercritical carbon dioxide precipitation, high-gravity-controlled precipitation, impinging-jet or vortex mixing can give arise to occurrence of amorphous materials during the production of inhalation powders.

• Stability of amorphous inhalation powders can be achieved by increasing the glass transition temperature (Tg) using API and/or excipients that have a high Tg.

• Surface treatment with hydrophobic components such as amino acids, metal stearates or hydrophobic API can protect the amorphous particles from recrystallization and deleterious effect of moisture on aerosol performance.

• Lowering of the residual water content in the powder after production plus protective packaging such as blister packs and aluminum pouches can help protect the amorphous inhalation powder during storage.

Declaration of interest

L Chen and D Chen work for Hangzhou Chance Pharmaceuticals which is developing inhalation products. The views presented in the manuscript are solely of the authors. There are no financial or any other interests that have inappropriately influenced the content in any way. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.