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Dry powder inhalation (DPI) products basically consist of a powder formulation and a device. The formulation, which contains active pharmaceutical ingredient(s) (APIs) micronized to inhalable particle size and a few excipients may, at first glance, appear simple. However, a large number of factors are critical to the performance of dry powder formulations for inhalation. Furthermore, many of these interact in complex ways. 24 June 2022 Inhalation Formulation development of adhesive mixtures for inhalation—A multi-factorial optimization challenge: Part 1 Considerations for APIs, excipients, composition and processing of dry powder formulations Kyrre Thalberg, PhD Drawings by Peter Elfman, MSc Emmace Consulting AB mulation development is therefore a complex and challenging task, typically involving a range of exper- imental design campaigns. e simplest type of adhesive mixture consists only of fine active pharmaceutical ingredient (API) par- ticles and (pharmaceutically inert) carrier particles, as schematically illustrated in Figure 2. Fine excip- ient particles and coating agents may be added to this mixture [1, 2]. Lactose monohydrate is, by far, the most common excipient and we will assume the use of lactose throughout this article, both for carrier and fine particle excipients, unless otherwise stated. As for coating agents, magnesium stearate (MgSt) is the most popular and now present in several prod- ucts on the market [3]. Regardless of the simplicity or complexity of the formulation, the API, excipient(s), composition and processing together determine the dispersibility of the powder, expressed by the fine Synopsis Dry powder inhalation (DPI) products basically consist of a powder formulation and a device. e formulation, which contains active pharmaceutical ingredient(s) (APIs) micronized to inhalable particle size and a few excipients may, at first glance, appear simple. How- ever, a large number of factors are critical to the per- formance of dry powder formulations for inhalation. Furthermore, many of these interact in complex ways. e articles in this two-part series will focus on adhesive mixtures for inhalation, also called ordered mixtures or carrier-based formulations. ese terms stem from the formulation structure of carrier particles with fine drug particles attached to their surfaces. In the first article, we will discuss considerations relating to the four parts that together define a dry powder formulation. In the second article, important modes of interaction will be analyzed, along with the interplay between the device and the for- mulation. Our vision is that in-depth knowledge of the four parts that define a formulation and the ways they interact can lead to improved formulation development in the future. Four parts define the dry powder formulation A dry powder inhalation (DPI) product, consisting of the device and the formulation, has four key parts which together define the formulation: the active pharmaceutical ingredient (API), excipient(s), com- position and processing. As illustrated in Figure 1, all of these interact with each other. Dry powder for- Figure 1 The four parts that together define an inhaled formulation and their interactions. Processing API Excipient Composition