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Inhalation August 2024 13 Typically, metastable solid forms exhibit greater solu- bility and dissolution rates compared to their thermo- dynamically stable counterparts, primarily because of differences in crystal lattice energies [16]. To evaluate this, two non-bioequivalent BDP pMDIs: QVAR ® (TEVA, Tel Aviv, Israel) and Sanas- thmax ® (Chiesi, Parma, Italy) were used to generate test particles. e QVAR and Sanasthmax formu- lations differed in the amount of ethanol cosolvent (8% and 10%, respectively) and the presence or absence of glycerol (0% and 1.3% respectively). e BDP powder raw material used to manufacture the pMDI formulations was crystalline and the particles emitted from the QVAR inhaler also displayed some degree of crystallinity, as indicated by powder X-ray diffraction (PXRD) analysis, with a diffraction pat- tern containing several distinct peaks differing from those of anhydrous BDP. Conversely, the particles emitted from the Sanasthmax inhaler yielded results with no peaks on the diffractogram, indicating their amorphous nature. Subsequently, the Franz cell tech- nique was employed to conduct in vitro dissolution testing under non-sink conditions for particles col- lected from QVAR and Sanasthmax on the second stage of a modified Twin Stage Impinger. After 60 minutes, approximately 73 ± 5% of the deposited BDP, displaying some crystallinity, was released from the QVAR particles, whereas only 9 ± 4% of BDP was released from Sanasthmax particles, which exhib- ited anhydrous characteristics [7]. surface and the surrounding environment during the drying step. Meanwhile, the propellant within the droplets continues to evaporate, creating inter- nal voids, facilitated by the rapid evaporation of propellant gas with a negative boiling point (e.g., HFA-134a at -26.3°C and HFA-152a at -24°C) at ambient temperatures [15]. e particle morphology of budesonide solution- based pMDIs utilizing HFA-134a with varying amounts of ethanol (5-30%, w/w) was investigated [15]. e study revealed that particles emitted from all formulations exhibited two distinct morphologies: smooth surface and coral-like surface morphology. Interestingly, an increase in ethanol percentage in the formulation, from 5% to 30%, led to a decrease in the percentage of irregular-shaped particles, from approximately 52% to 2.5%. is observation sug- gests that higher ethanol concentrations slow droplet evaporation, thereby delaying the increase in surface viscosity and favoring drying with a smooth surface, as observed in another recent study [14]. A subsequent study investigated the impact of differ- ent morphological properties from three propellant formulations (HFA-134a, the newer, eco-friendlier HFO-1234ze(E) and HFA-152a) on in vitro drug dissolution of maturated beclomethasone dipropio- nate particles generated from solution-based pMDIs. Maturated particles were collected on a modified Anderson Cascade Impactor that housed eight Snap- well inserts on Stage 5, at a flow rate of 28 L/min. e study found that, although the pMDI formu- lations containing HFA-152a and HFA-134a exhib- ited similar ratios of corrugated/rough particles to smooth/spherical particles, HFA-134a produced smaller rough and smooth particles compared to HFA-152a. e HFO-1234ze(E) formulation pro- duced a significantly higher percentage of smooth/ spherical particles and a corresponding lower per- centage of corrugated/rough particles collected on that stage of the ACI (Figures 2A, 2C, 2D) [5]. e differences in the morphologies and sizes of the particles resulted in different dissolution rates of drug particles over a four-hour period with the fol- lowing rank order: HFA-134a > HFO-1234ze(E) > HFA-152a (Figure 2B). Considering particles were collected from the same stage of the ACI, (which has a consistent aerodynamic particle size), a decrease in geometric particle size and an increase in the pro- portion of corrugated/rough particles led to faster dissolution. is effect can be attributed to the larger surface area of the particles, which enhanced the dissolution kinetics. Solid state properties e rate of dissolution is also significantly influenced by the solid state characteristics of the API, whether those characteristics are amorphous or crystalline.