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Inhalation APRIL 2020 13 An advantage of focused-beam techniques is that they can be made simultaneously. By measuring the total mass of spray and the amount of drug present in the spray at the same time, the instantaneous mass fraction of drug inside the spray is revealed. is is shown in Fig- ure 4 (black line, lower right) with the shaded region indicating uncertainty. is measurement is e ectively independent of the number density of droplets in the spray and reveals that the underlying concentration of the drug inside the droplets decays during the spray. is can be compared to the expected concentration of the drug in the formulation. As has been known for some time, a signi cant portion of the drug remains in other molecule in the formulation. In practice, these elements are chlorine (17) through cerium (58). Unlike visible uorescence, the X-ray photons can escape the dense core of the spray. A detector that can discriminate photons based on their energy is used to capture them, as shown in Figure 3. These experiments were con- ducted at the 7-BM beamline of the Advanced Photon Source at Argonne National Laboratory. A sample result for an HFA-134a formulation with 15% co-sol- vent and 3.38 µg/µL ipratropium bromide is shown in Figure 4 (red line, top right). e uorescent tracer is the bromine atom in the ipratropium bromide mole- cule; no dopant is required. Figure 3 Schematic diagram of focused-beam techniques for pMDI sprays; radiography, elastic scattering and uorescence. y x z Formulation in ow Co- ow Monochromatic X-ray beam Fluorescence Collimator Fluorescence detector Spray pMDI nozzle Scattering Transmission photodiode (radiography) Scattering photodiode Figure 4 Sample results from scattering (blue) and uorescence (red) measurements in a solution-based pMDI spray at x/D =1.5. Drug only Total Spray 0.5 0.4 0.3 0.2 0.1 0.0 60% 50% 40% 30% 20% 10% 0% 600 500 400 300 200 100 Drug only [µg/mm] Time [s] Percent canister concentration Drug only [µg/mm] 0.0 0.2 0.4 0.6 0.8 1.0 1.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2 EEC | mEEC | BAC | NAC | ePRO | eNO | SPUTUM Contact Cliantha Research today for your program planning and clinical trial conduct at: Cynthia Day O'Brien Senior Director, Business Development +1-507-208-5012 cobrien@cliantha.com We are a full-service, global, clinical stage CRO We use innovative approaches to fast track product development We specialize in respiratory drug development We help Innovators & Generics bring inhaler products to market "Because it's never too early to talk about clinical development"