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Omar S Usmani - One of the best experts on this subject based on the ideXlab platform.
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pulmonary deposition of budesonide glycopyrronium formoterol fumarate dihydrate metered dose inhaler formulated using co suspension delivery technology in healthy male subjects
European Journal of Pharmaceutical Sciences, 2020Co-Authors: Samuel Israel, Ashish Kumar, Kiernan Deangelis, Magnus Aurivillius, Paul Dorinsky, Nicolas Roche, Omar S UsmaniAbstract:Abstract This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two Actuations of BGF MDI (160/7.2/4.8 μg per Actuation) radiolabelled with 99mTc, not exceeding 5 MBq per Actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
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gamma scintigraphic pulmonary deposition study of glycopyrronium formoterol metered dose inhaler formulated using co suspension delivery technology
European Journal of Pharmaceutical Sciences, 2018Co-Authors: Glyn Taylor, Simon Warren, Sarvajna Kumar Dwivedi, Mark Sommerville, Lauren Mello, Chad Orevillo, Andrea Maes, Ubaldo J Martin, Omar S UsmaniAbstract:Abstract This gamma scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β 2 -agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two Actuations of GFF pMDI (7.2/5.0 μg per Actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with 99m Tc, up to 5 MBq per Actuation. Gamma scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤ 0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.
William F. S. Sellers - One of the best experts on this subject based on the ideXlab platform.
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Asthma pressurised metered dose inhaler performance: propellant effect studies in delivery systems
Allergy Asthma & Clinical Immunology, 2017Co-Authors: William F. S. SellersAbstract:Background Current pressurised metered dose asthma inhaler (pMDI) propellants are not inert pharmacologically as were previous chlorofluorocarbons, have smooth muscle relaxant‚ partial pressure effects in the lungs and inhaled hydrofluoroalkane 134a (norflurane) has anaesthetic effects. Volumes of propellant gas per Actuation have never been measured. Methods In-vitro studies measured gas volumes produced by pMDIs on air oxygen (O_2) levels in valved holding chambers (VHC) and the falls in O_2% following Actuation into lung ventilator delivery devices. Results Volumes of propellant gas hydrofluoroalkane (HFA) 134a and 227ea and redundant chlorofluorocarbons (CFC) varied from 7 ml per Actuation from a small salbutamol HFA inhaler to 16 ml from the larger. Similar-sized CFC pMDI volumes were 15.6 and 20.4 ml. Each HFA salbutamol inhaler has 220 full volume discharges; total volume of gas from a small 134a pMDI was 1640 ml, and large 3885 ml. Sensing the presence of liquid propellant by shaking was felt at the 220th discharge in both large and small inhalers. Because of a partial pressure effect, VHC O_2% in air was reduced to 11% in the smallest 127 ml volume VHC following 10 Actuations of a large 134a salbutamol inhaler. The four ventilator delivery devices studied lowered 100% oxygen levels to a range of 93 to 81% after five Actuations, depending on the device and type of pMDI used. Conclusion Pressurised inhaler propellants require further study to assess smooth muscle relaxing properties.
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Asthma pressurised metered dose inhaler performance: propellant effect studies in delivery systems.
Allergy Asthma & Clinical Immunology, 2017Co-Authors: William F. S. SellersAbstract:Current pressurised metered dose asthma inhaler (pMDI) propellants are not inert pharmacologically as were previous chlorofluorocarbons, have smooth muscle relaxant‚ partial pressure effects in the lungs and inhaled hydrofluoroalkane 134a (norflurane) has anaesthetic effects. Volumes of propellant gas per Actuation have never been measured. In-vitro studies measured gas volumes produced by pMDIs on air oxygen (O2) levels in valved holding chambers (VHC) and the falls in O2% following Actuation into lung ventilator delivery devices. Volumes of propellant gas hydrofluoroalkane (HFA) 134a and 227ea and redundant chlorofluorocarbons (CFC) varied from 7 ml per Actuation from a small salbutamol HFA inhaler to 16 ml from the larger. Similar-sized CFC pMDI volumes were 15.6 and 20.4 ml. Each HFA salbutamol inhaler has 220 full volume discharges; total volume of gas from a small 134a pMDI was 1640 ml, and large 3885 ml. Sensing the presence of liquid propellant by shaking was felt at the 220th discharge in both large and small inhalers. Because of a partial pressure effect, VHC O2% in air was reduced to 11% in the smallest 127 ml volume VHC following 10 Actuations of a large 134a salbutamol inhaler. The four ventilator delivery devices studied lowered 100% oxygen levels to a range of 93 to 81% after five Actuations, depending on the device and type of pMDI used. Pressurised inhaler propellants require further study to assess smooth muscle relaxing properties.
Glyn Taylor - One of the best experts on this subject based on the ideXlab platform.
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gamma scintigraphic pulmonary deposition study of glycopyrronium formoterol metered dose inhaler formulated using co suspension delivery technology
European Journal of Pharmaceutical Sciences, 2018Co-Authors: Glyn Taylor, Simon Warren, Sarvajna Kumar Dwivedi, Mark Sommerville, Lauren Mello, Chad Orevillo, Andrea Maes, Ubaldo J Martin, Omar S UsmaniAbstract:Abstract This gamma scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β 2 -agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two Actuations of GFF pMDI (7.2/5.0 μg per Actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with 99m Tc, up to 5 MBq per Actuation. Gamma scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤ 0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.
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safety and pharmacokinetics of dihydroergotamine mesylate administered via a novel tempo inhaler
Headache, 2008Co-Authors: Stephen B Shrewsbury, Robert O Cook, Glyn Taylor, Ceri Edwards, Nabih M RamadanAbstract:Objective.— We investigated the pulmonary absorption of dihydroergotamine (DHE) mesylate and compared the safety, pharmacokinetic, and metabolic profile of 4 different doses of orally inhaled DHE delivered by the Tempo™ Inhaler (MAP Pharmaceuticals Inc., Mountain View, CA, USA) with 1.0 mg intravenously (IV) administered DHE in 18 healthy subjects. Methods.— Safety was measured by monitoring adverse events, vital signs, electrocardiograms, spirometry, and changes in biochemical and hematological laboratory values. Liquid chromatography, tandem mass spectrometry was used to determine plasma DHE levels while Cmax, tmax, AUC0-6, AUC0-48, AUC0-inf, and t1/2 of parent DHE and the major bioactive metabolite, 8′OH-DHE. Pharmacokinetic parameters and qualitative spectrograms for DHE and metabolites for all treatment groups were compared after inhaled DHE (MAP0004) and IV DHE 1.0 mg. Geometric means and 90% confidence intervals of log-transformed data were calculated and the ratio of means compared. Results.— Inhaled DHE resulted in rapid systemic absorption with pharmacokinetic parameters of both parent DHE and 8′OH-DHE similar to those achieved after a 3-minute IV infusion. Post-peak (tmax∼12 minutes) DHE concentrations achieved after 4 Actuations (∼0.88 mg respirable dose) of MAP0004 were comparable to those detected after IV administration. The systemic exposure to DHE after 6 Actuations of MAP0004 was slightly greater than that achieved after IV administration (geometric mean AUC0-inf ratio = 1.24). Conclusion.— The 4-Actuation delivery was well tolerated and provided systemic levels of DHE and 8′OH-DHE slightly lower than IV administration and predicted levels.
Samuel Israel - One of the best experts on this subject based on the ideXlab platform.
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pulmonary deposition of budesonide glycopyrronium formoterol fumarate dihydrate metered dose inhaler formulated using co suspension delivery technology in healthy male subjects
European Journal of Pharmaceutical Sciences, 2020Co-Authors: Samuel Israel, Ashish Kumar, Kiernan Deangelis, Magnus Aurivillius, Paul Dorinsky, Nicolas Roche, Omar S UsmaniAbstract:Abstract This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two Actuations of BGF MDI (160/7.2/4.8 μg per Actuation) radiolabelled with 99mTc, not exceeding 5 MBq per Actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
Ashish Kumar - One of the best experts on this subject based on the ideXlab platform.
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pulmonary deposition of budesonide glycopyrronium formoterol fumarate dihydrate metered dose inhaler formulated using co suspension delivery technology in healthy male subjects
European Journal of Pharmaceutical Sciences, 2020Co-Authors: Samuel Israel, Ashish Kumar, Kiernan Deangelis, Magnus Aurivillius, Paul Dorinsky, Nicolas Roche, Omar S UsmaniAbstract:Abstract This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two Actuations of BGF MDI (160/7.2/4.8 μg per Actuation) radiolabelled with 99mTc, not exceeding 5 MBq per Actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
