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Inhalation JUNE 2022 29 Acknowledgement is work was supported by the Swedish Foundation for Strategic Research. References 1. Telko M, Hickey A, 2005. Dry powder inhaler formulation. Respir. Care. 50 (9), 1209-1227. 2. De Boer A, alberg K, 2021. Dry powder inhal- ers (DPIs). Book chapter in: Inhaled medicines. Optimizing development by integration of in sil- ico, in vitro and in vivo approaches. Eds. Kassinos S, Bäckman P, Conway J, Hickey A. Academic Press. Ch. 5, 99-146. 3. Shur J, Price R, Lewis D, Young P, Woollam G, Singh D, Edge S., 2016. From single excipients to dual excipient platforms in dry powder inhaler prod- ucts. Int. J. Pharm. 514, 374-383. 4. Trofast E, Briggner L, 1998. Process for condition- ing substances. US Patent 5,709,884. 5. Vehring R, 2008. Pharmaceutical particle engineer- ing via spray drying. Pharm. Res. 25 (5), 999-1022. 6. Grasmeijer F, Grasmeijer N, Hagedoorn P, Frijlink H, de Boer A, 2015. Recent advances in the funda- mental understanding of adhesive mixtures for inha- lation. Curr. Pharm. Des. 21 (40) 5900-5915. 7. Weiss C, McLoughlin P, Cathcart H, 2015. Char- acterisation of dry powder inhaler formulations using atomic force microscopy. Int. J. Pharm. 494, 393-407. 8. Young P, Cocconi D, Colombo P, Bettini R, Price R, Steele D, Tobyn M, 2002. Characterization of a surface modi ed powder inhalation carrier prepared by particle smoothing. J. Pharm. Pharmacol. 54, 1339-1344. 9. Begat P, Morton D, Staniforth J, Price R, 2004. e cohesive-adhesive balance in dry powder inhaler formulations 1: Direct quanti cation by atomic force microscopy. Pharm. Res. 21, 1591-1597. 10. Bunker M, Roberts C, Davies M, James M, 2006. A nanoscale study of particle friction in a phar- maceutical system. Int. J. Pharm. 325, 163-171. 11. alberg K, Berg E, Fransson M, 2012. Mod- eling dispersion of dry powders for inhalation. e concepts of total nes, cohesive energy and interac- tion parameters. Int. J. Pharm. 427, 224-233. 12. Nguyen D, Remmelgas J, Niklasson Björn I, van Wache B, alberg K, 2018. Towards quantitative prediction of the performance of dry powder inhal- ers by multi-scale simulations and experiments. Int. J. Pharm. 547, 31-43. 13. Kinnunen H, Hebbink G, Peters H, Huck D, Makein L, Price R, 2015. Extrinsic lactose nes improve dry powder inhaler formulation perfor- mance of a cohesive batch of budesonide via agglom- It should be emphasized that the mass of the carrier is key both to mixing energy and mixing force. As carrier mass is proportional to the cube of the parti- cle diameter, this shows the major impact of carrier particle size in high shear mixing. In a recent study [19], the mixing energy concept was utilized for smearing of coating agent onto lac- tose carrier. Two single crystal carrier grades, Lacto- hale LH100 (DFE Pharma, Goch, Germany) and Respitose SV003 (DFE Pharma, Goch, Germany), were coated using 1.0 % L-leucine. Respitose SV003, which is the smaller carrier, was coated at a higher speed and for longer processing times. When plot- ted as function of the applied ME, however, the two curves become perfectly superimposed, (Figure 6). is illustrates the validity of the ME concept and shows that for a smaller (i.e., lighter) carrier, a higher speed and/or a longer coating time is needed to achieve the same degree of coating. Looking to Part 2 of this series In this Part 1 article, we have considered four key parts that de ne a dry powder formulation: the active pharmaceutical ingredient (API), excipients, composition and processing. In the second article, we will show that the mixing process may strongly a ect the dispersibility of the formulation and that the applied mixing energy can be used to under- stand and predict the ne particle fraction. In addi- tion, the interplay between the formulation and the device will be discussed. Figure 6 The degree of surface coating plotted versus the applied mixing energy (ME) for coating of lactose carriers SV003 (squares) and LH100 (triangles), both from DFE Pharma, Goch, Germany, with 1.0% L-leucine. The t is made based on the combined dataset. Error bars indicate ± 1 standard deviation. (Data from reference 19.) 0.0 0.2 0.4 0.6 0.8 1.0 Mixing energy (mJ/carrier) Degree of coating (%) 60 50 40 30 20 10 0 SV003 LH100 Fit