The Preparation of a Radiolabelled Aerosol of Nedocromil Sodium for Administration by Metered-Dose Inhaler that Accurately Preserves Particle Size Distribution of the Drug

Summers, Quentin; Clark, Andrew R.; Hollingworth, Ann; Fleming, John; Holgate, Stephen T.

doi:10.1007/bf03258246

Cited by 33 publications

(6 citation statements)

References 25 publications

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“…The order in which the spacer devices were used for each rabbit was randomized. Labeling of salbutamol pressurized metered-dose inhaler was performed using a variation of the technique previously described by Summer (15). Pertechnetate (99m TcO 4 Ϫ ) was extracted from saline using methyl ethyl ketone.…”

Section: In Vivo Studymentioning

confidence: 99%

Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

et al. 2001

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Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles Ͻ5.8 m in diameter (NES-spacer ϭ Babyhaler Ͼ Aerochamber-Infant; p Ͻ 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52-5.40% of the delivered dose) but greater with the NESspacer than with the Aerochamber-Infant or the Babyhaler (5.40 Ϯ 2.40%, 2.91 Ϯ 0.86%, 0.52 Ϯ 0.46%, respectively; p ϭ 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants. Small-volume spacer devices fitted with a face mask and inspiratory/expiratory valves have been developed for delivering pressurized metered-dose inhaler drugs to infants and newborns with various respiratory diseases (1-4). However, little is known about the ability of these spacer devices to deliver a significant amount of drug to the lungs of spontaneous breathing infants and a fortiori in intubated and mechanically ventilated infants and newborns.The radiotracer technique is the only method available for direct estimation of aerosol deposition in vivo. This technique is commonly used in adults, and has been used in several studies in infants (5-7). However, the exposure of small infants to radioisotopes remains a concern. Thus, performance is often projected from in vitro experiments (8 -10) or in vitro lung models (11,12), with data obtained at lower inspiratory flow rates and higher tidal volumes through the spacer devices than what would be encountered in clinical practice. Animal "infant" models (13, 14) may be suitable alternatives to assess pulmonary deposition of labeled drugs. Usually, rabbits are tracheotomized, mechanically ventilated, and killed, but this animal model poorly reflects the lung deposition of drug administered through spacer devices in spontaneously breathing children. Because oropharyngeal ...

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Section: In Vivo Studymentioning

confidence: 99%

Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

et al. 2001

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“…After back- Histogram of the relative deposition of salbutamol and 9"Tc after actuation of radiolabelled salbutamol MDIs into an Andersen eight stage cascade impactor. Effective cut off diameters (at a flow rate of 28-3 1/min) for stages 0-7 are 9 0, 5 8, 4 7, 3 3, 2 1, 1 1, 0-7, and 04 pm, respectively. ground correction the geometric mean counts in those areas of interest were calculated from the appropriate pair of anterior and posterior counts.…”

Section: Batteriesmentioning

confidence: 99%

Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler.

Farr

Rowe²,

Rubsamen³

et al. 1995

Thorax

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Background -Gamma scintigraphy was employed to assess the deposition of aerosols emitted from a pressurised metered dose inhaler (MDI) contained in a microprocessor controlled device (SmartMist), a system which analyses an inspiratory flow profile and automatically actuates the MDI when predefined conditions of flow rate and cumulative inspired volume coincide. Methods -Micronised salbutamol particles contained in a commercial MDI (Ventolin) were labelled with 99m-technetium using a method validated by the determination of (1) aerosol size characteristics ofthe drug and radiotracer following actuation into an eight stage cascade impactor and (2) shot potencies ofthese non-volatile components as a function of actuation number. Using nine healthy volunteers in a randomised factorial interaction design the effect of inspiratory flow rate (slow, 30 1min; medium, 90 Vmin; fast, 270 /min) combined with cumulative inspired volume (early, 300 ml; late, 3000 ml) was determined on total and regional aerosol lung deposition using the technique of gamma scintigraphy. Results -The SmartMist firing at the mediumlearly setting (medium flow and early in the cumulative inspired volume) resulted in the highest lung deposition at 18-6 (1.42)%. The slow/early setting gave the second highest deposition at 14a1 (2.06)% with the fastllate setting resulting in the lowest (7.6 (1-15)%). Peripheral lung deposition obtained for the mediumlearly (9.1 (0.9)%) and slowlearly (7.5 (1.06)%) settings were equivalent but higher than those obtained with the other treatments. This reflected the lower total lung deposition at these other settings as no difference in regional deposition, expressed as a volume corrected central zone:peripheral zone ratio, was apparent for all modes of inhalation studied. Conclusions -The SmartMist device allowed reproducible actuation of an MDI at a preprogrammed point during inspiration. The extent ofaerosol deposition in the lung is affected by a change in firing point and is promoted by an inhaled flow rate of up to 90 1/min -that is, the slow and medium setting used in these studies. (Thorax 1995;50:639-644)

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“…However, this information is probably misleading as in all of these studies the aerosol cloud was sized after the propellant had been allowed to evaporate wholly or partially, leaving only drug particles. That the aerosol is emitted at a velocity of 30 m/sec (70 mph) [20] may be the major cause of the poor pulmonary deposition efficiency of such aerosols, which is of the order of 10-15% of the delivered dose, the majority of the aerosol impacting in the oropharynx [21], Clearly, this is not the only reason for such a small deposition efficiency, as the MMAD of terbutaline delivered by MDI is 36 fim at the actuator orifice, decreasing to 12 iin\ at a distance of 10 cm from the actuator [22], Our own studies with nedocromil sodium (Tilade®, Fisons) show it to have an MMAD of about 16 /um, with a GSD of 5-3 [23], and perusal of data from Newman et al [21] reveals that the MMAD of Intal® MDI (1 mg) is greater than 22 /im. The wide spread of droplet sizes ensures that a proportion of the aerosol is of a suitable size to enter the lung.…”

Section: Drug Deliverymentioning

confidence: 99%

“…Most studies have utilized monodispersed teflon particles labelled with Tc''" and delivered by MDI, yielding valuable information regarding the deposition of the particles; however, such studies cannot substitute for information regarding the pulmonary deposition of drug solutions delivered by MDL Many investigators have used radioaerosol delivered by jet nebulizer as this is a more accessible system. We have recently described a technique, modified from that of Kohler et al [31], for the addition of Tc''" to MDIs containing nedocromil sodium [23]. Because this technique preserves the particle size distribution ofthe aerosol, and because the radio-label is closely associated with the drug, it allows the study ofthe lung deposition of this agent, coupled with the study of its pharmacokinetics and pharmacodynamics.…”

Section: Drug Deliverymentioning

confidence: 99%

Inhaled drugs and the lung

Summers

1991

Clin Experimental Allergy

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The Preparation of a Radiolabelled Aerosol of Nedocromil Sodium for Administration by Metered-Dose Inhaler that Accurately Preserves Particle Size Distribution of the Drug

Cited by 33 publications

References 25 publications

Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

Delivery of Salbutamol Pressurized Metered-Dose Inhaler Administered Via Small-Volume Spacer Devices in Intubated, Spontaneously Breathing Rabbits

Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler.

Inhaled drugs and the lung

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