Issue link: https://www.e-digitaleditions.com/i/1515319
28 February 2024 Inhalation References 1. Weers, J.G., Miller, D.P. Formulation Design of Dry Powders for Inhalation. Journal of Pharmaceu- tical Sciences 2015, 104, 3259-3288, doi:10.1002/ jps.24574. 2. Carrigy, N.B., Ordoubadi, M., Liu, Y., Melhem, O., Barona, D., Wang, H., Milburn, L., Ruzycki, C.A., Finlay, W.H., Vehring, R. Amorphous Pullulan Tre- halose Microparticle Platform for Respiratory Deliv- ery. International Journal of Pharmaceutics 2019, 563, 156-168, doi:10.1016/j.ijpharm.2019.04.004. 3. Vehring, R., Foss, W.R., Lechuga-Ballesteros, D. Particle Formation in Spray Drying. Journal of Aerosol Science 2007, 38, 728-746, doi:10.1016/j. jaerosci.2007.04.005. 4. Boraey, M.A., Vehring, R. Diffusion Controlled Formation of Microparticles. Journal of Aero- sol Science 2014, 67, 131-143, doi:10.1016/j. jaerosci.2013.10.002. 5. Ordoubadi, M., Wang, H., Vehring, R. Mech- anistic Formulation Design of Spray-Dried Pow- ders. KONA 2023, 40, 149-171, doi:10.14356/ kona.2023012. 6. Rosen, M.J., Kunjappu, J.T. Surfactants and Inter- facial Phenomena; John Wiley & Sons, 2012; ISBN 0-470-54194-6. 7. Lechuga-Ballesteros, D., Charan, C., Stults, C.L.M., Stevenson, C.L., Miller, D.P., Vehring, R., Tep, V., Kuo, M. Trileucine Improves Aerosol Per- formance and Stability of Spray‐Dried Powders for Inhalation. Journal of Pharmaceutical Sciences 2008, 97, 287-302, doi:10.1002/jps.21078. 8. Li, L., Sun, S., Parumasivam, T., Denman, J.A., Gengenbach, T., Tang, P., Mao, S., Chan, H.-K. L-Leucine as an Excipient Against Moisture on In Vitro Aerosolization Performances of Highly Hygroscopic Spray-Dried Powders. European Jour- nal of Pharmaceutics and Biopharmaceutics 2016, 102, 132-141, doi:10.1016/j.ejpb.2016.02.010. 9. Adler, M., Lee, G. Stability and Surface Activity of Lactate Dehydrogenase in Spray‐Dried Trehalose. Journal of Pharmaceutical Sciences 1999, 88, 199- 208, doi:10.1021/js980321x. 10. Ordoubadi, M., Gregson, F.K.A., Wang, H., Carrigy, N.B., Nicholas, M., Gracin, S., Lechuga- Ballesteros, D., Reid, J.P., Finlay, W.H., Vehring, R. Trileucine as a Dispersibility Enhancer of Spray- Dried Inhalable Microparticles. Journal of Con- trolled Release 2021, 336, 522-536, doi:10.1016/j. jconrel.2021.06.045. 11. Nuzzo, M., Millqvist-Fureby, A., Sloth, J., Ber- genstahl, B. Surface Composition and Morphology of Particles Dried Individually and by Spray Drying. Drying Technology 2015, 33, 757-767, doi:10.1080 /07373937.2014.990566. stituents. is comparison allows for the design of optimal formulation and process parameters. e objective is to ensure that the shell formation tran- spires well in advance of the solidification of any other API or excipient intended to remain within the particle's core. is simplified approach can provide the essential insights to reduce the need for an extensive set of experimental iterations, in alignment with the principles of quality by design, which has been successfully applied to a diverse range of formulations [10, 21, 22]. As an exam- ple, the drying time of an 8 mm aqueous droplet containing 1 mg/mL trileucine and 49 mg/mL tre- halose at 75 °C is 14 ms. e time anticipated for the trileucine to reach surface saturation is roughly 1.6 ms, while trehalose is expected to solidify in approximately 12 ms [10]. Such data suggests that, in this formulation, trileucine would likely serve as an effective shell former at this concentration. For surface-active shell formers, two thresholds can be considered: the first is the time to reach a satu- rated monolayer, and the second is the actual solid- ification time of the material. For example, at low concentrations, leucine, possessing relatively weak surface activity, can make a monolayer before hav- ing enough time to undergo nucleation and crystal growth. In such cases, the surface energy of the dried particles is reduced slightly, improving the aerosol performance. To benefit from the full shell-form- ing potential of leucine, the formulation should be designed in such a way that the crystallization instance of leucine is also much smaller than the instances of solidification of other compounds. Conclusion is article delves into the mechanisms under- lying shell formation during the spray drying of particles. Two predominant mechanisms were iden- tified: surface accumulation stemming from a high Péclet number and surface adsorption due to sur- face activity. As there is growing interest in crafting carrier-free powders with exceptional aerosol char- acteristics, it is beneficial for formulators to discern the shell-formation mechanisms of dispersibility enhancing candidates. Doing so can promote effi- cient and dependable formulation design, based on a comprehensive grasp of the entire process. is can lead to fewer experimental iterations, subsequently decreasing costs and uncertainties during the initial phases of product development.