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12 August 2024 Inhalation brane was then placed in the donor compartment of a Transwell system. Particle morphology Production of particles from solution-based pMDIs typically involves atomization, followed by matura- tion steps. Induced by high-speed airflow when the user actuates the inhaler, atomization forms droplets. Aerosol maturation occurs when the droplets start to evaporate and lose solvent and propellant content, within the patient's respiratory system. Smooth and rough surface microparticle morphol- ogies have been observed under scanning electron microscopy (SEM) in a few recent studies [14, 15]. It was hypothesized that the final formed particle morphology is governed by a combination of atom- ization and maturation phases [15]. It was sug- gested that during the atomization step for pMDIs, the uneven vaporization of the propellant in the expansion chamber of the actuator may result in various droplet compositions. Initially, all types of droplets undergo a brief co-evaporation process. Subsequently, a thin surface crust forms rapidly, due to intense energy transfer between the droplet tionally, it was observed that the dissolution of poorly soluble FP, but not highly soluble FN, was dependent on the aerosol mass kinetics. e study demonstrated that as the mass of FP aerosols increased from 9 μg to 41 μg to 101 μg, slower dissolution and permeation were observed. Emitted aerosol particle size It is well accepted that aerosol particle size significantly influences dissolution in inhalation delivery. Smaller particles, typically less than 3 μm are advantageous, as they offer increased surface area for dissolution, lead- ing to enhanced drug absorption and bioavailability in the lungs. Larger particles may deposit in the upper respiratory tract and be less efficiently absorbed, impacting the effectiveness of therapy. A study by Arora, et al. [13] demonstrated that budesonide aerosol particles with smaller sizes (2.1- 3.3 μm), collected on stage 4 of the ACI, demon- strated quicker and more extensive dissolution and permeation compared to larger particles (4.7-5.8 μm) generated from stage 2. is difference is reflected in their respective in vitro drug dissolution half-lives of 1.8 ± 0.1 hours and 3.9 ± 0.9 hours, when the mem- Figure 2 A) Scanning electron micrographs of the maturated particles collected on stage 5 of the modified ACI from pMDI formulations produced using different propellants. B) Dissolution profiles of BDP particles deposited on stage 5 of the modified ACI measured over 4 hours. Results are reported as average ± SD, (n = 8). SEM analysis of maturated drug particles morphologies in terms of: C) percentage of smooth and corrugated particles and D) mean geometric size of the particles. *p-value < 0.05. Results and figures were adapted, with permission, from reference 5. 60 40 20 0 Time (minutes) HFA-152a HFO-1234ze(E) HFA-134a 0 100 200 B C A Cumulative Drug Dissolved (%) HFA-152a HFO-1234ze(E) HFA-134a * * * * * 0 50 100 % Particles HFA-134a HFA-152a HFO-1234ze(E) HFA-134a HFA-152a HFO-1234ze(E) Smooth/Spherical Corrugated/Rough Mean Geometric Size (µm) 2.5 2.0 1.5 1.0 0.5 0.0 HFA-152a HFO-1234ze(E) HFA-134a D