ABSTRACT
Formulation of proteins and peptides often is more challenging than formulation of small molecules, because of the important role of protein conformation as well as the potential for numerous chemical degradation pathways (1,2). This fact, coupled with the necessity of using a device to generate an aerosol, augments the challenge considerably. A developed formulation must provide one to two years of stability on storage (preferably room temperature), and it also must meet additional requirements that are unique to its delivery as an aerosol. First, the formulation must not cause adverse pulmonary reactions such as cough or bronchoconstriction; it must be safe for delivery to the lungs; and any excipients used should preferably be generally-regarded-as-safe (GRAS). Second, the formulation may also have to be designed to minimize interactions with the inhaler component materials, where the drug-contacting materials should be of medical grade with acceptable leachable profi les. Finally, the formulation must stabilize the protein suffi ciently to ensure that the protein survives the rigors of the aerosolgeneration process. In addition to these challenges, the development and ultimate approval of an aerosol formulation often goes hand in hand with the development and/or use of a particular device, often requiring approval as, and product release as, a drug/device combination.
