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Inhalation August 2024 15 Dissolution media As summarized in Table 1, researchers have utilized various dissolution media, ranging from phosphate buffers (PBS 7.4) to more biorelevant simulated lung fluids (such as Gamble's solution), with or without the addition of surfactants (e.g., sodium dodecyl sul- fate (SDS)) to study dissolution of maturated pMDI aerosols. ere are several reasons for using different solvent systems, including: • Enhancing the physiological relevance of in vitro tests • Maximizing the accuracy of in vivo predictions • Increasing drug solubility in the receptor compartment • Overcoming challenges related to limitations of analytical techniques • Maintaining sink conditions over 180 minutes) compared to glycerol-free particles (58.0% ± 2.9% over 60 minutes) when measured using a Franz diffusion cell, despite having similar aerodynamic properties, including equivalent parti- cle size distributions and fine particle fraction [21]. Ex vivo research on BDP pMDI products also sug- gests that a different percentage of glycerol in QVAR and Sanasthmax may affect drug dissolution after aerosol deposition in the lungs [22]. In summary, the dissolution process in ethanol- propellant solution pMDIs is closely linked to the ethanol concentration. Additionally, the choice of propellant with varying boiling points within the formed droplet, along with the presence of non- volatile excipients, collectively influence the rate of evaporation. Further, this rate of evaporation ulti- mately determines whether particles can progressively dry with a smooth or irregular surface geometry as the residual boiling liquid escapes from the particles. Dissolution Apparatus API/Formulation or Commercial Product Sample Collection Instrument Dissolution Medium Rotation Speed or Flow Rate Reference Transwell™ System Fluticasone propionate (FP) Flixotide ® 50 μg pMDI; Beclomethasone dipropionate (BDP) QVAR ® 50 μg pMDI TSI 600 μL medium (Gamble's solution, simulated lung fluid (SLF), or water with 0.5% sodium dodecyl sulfate (SDS)), fresh medium replaced for each sampling point N/A [4] BDP pMDI containing 8% w/w ethanol ACI with 3D-printed ACI plate 2 mL PBS 7.4, 200 μL taken for each sampling point N/A [5] 100 µg/50 µl BDP containing ethanol and glycerol NGI with 3D-printed NGI plate 2 mL PBS 7.4, 200 μL taken for each sampling point N/A [6] Franz Cell BDP, QVAR and Sanasthmax ® Modified TSI 0.1 w/v SDS in 0.1 M phosphate buffer, pH 7.4, 300 μL of dissolution medium sampled for each time point N/A [7] DissolvIt ® System FP, Flixotide pMDI DissolvIt System with microscope glass coverslips 5.7 μL SLF 0.4 mL/min [8] USP Method 2 (Paddle) Albuterol sulfate (AS) Ventolin ® NGI equipped with impaction insert 300 mL SLF, 3 mL of dissolution medium sampled for each time point 50, 75 and 100 rpm [9] Flow-Through Triamcinolone acetonide, Azmacort ® 200 μg ACI with USP induction port SLF 0.7 ml/min [10] Transwell™ System (Corning, Corning, New York, US) DissolvIt ® System (Inhalation Sciences, Huddinge, Sweden) Flixotide ® (GSK, Brentford, UK) QVAR ® (TEVA, Tel Aviv, Israel) Sanasthmax ® (Chiesi, Parma, Italy) Ventolin ® (GSK, Brentford, UK) Azmacort ® (Sanofi-Aventis, Paris, France) Table 1 Dissolution Methods Employed to Assess Dissolution of Deposited Microparticles from pMDIs