Confinement–Segregation Theory to Explain the Formation Mechanism of Peptide-Containing Particles in Metered Dose Inhalers

Understanding how to formulate peptides into metered dose inhalers (MDIs) is a bottleneck issue hampering the clinical translation of relevant products. In our previous studies, a bottom–up method to prepare peptide-containing particles for MDIs was reported. Nevertheless, the formation mechanism of the particles remains unclear. In this work, considering the production workflow, a confinement–segregation theory was put forward as a hypothesis to explain the formation mechanism. Confinement and segregation were two major processes during formation, and their definitions are provided in detail. Based on the theory, some factors influencing particle formation were also discussed, which promoted future formulation design. It is believed that the proposed theory will provide new insights into the study of peptide-containing MDIs and boost their clinical translation.