ABSTRACT
Distinct to other pharmaceutical dose forms, there is no existing Scale-Up and Post-Approval Changes guidance that details required in vitro and in vivo studies to support changes to manufacturing process, equipment, and scale for orally inhaled drug products (OIDPs). This chapter discusses scale considerations restricted to typical unit operations of the manufacturing process for a dry powder inhaler which involve a number of consecutive operations of powder handling and powder transfer—particle size reduction (micronization), powder blending, and powder filling. The formulation of inhalation powders typically contains particle size-reduced drug substance(s), a larger particle size excipient (carrier), and potentially additional components (e.g. magnesium stearate, leucine) to assure product performance and/or chemical/physical stability. Reproducible subdivision of inhalation powders at low dose into the inhalation powder primary pack (which may be a capsule, blister, reservoir, etc.) is challenging due to the typically low unit dose weight, which can range from <10 mg and up to 50 mg.
