In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices

Barry, PW; O’Callaghan, Chris

doi:10.1183/09031936.97.10061345

Cited by 70 publications

(35 citation statements)

References 13 publications

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“…We washed the spacer devices with lukewarm water and allowed them to dry at room air. Clark (20) demonstrated that washing a plastic spacer device (Volumatic, GlaxoSmithKline) in water was as effective as an antistatic paint in reducing the effects of static charge on salbutamol delivery, but other authors (8,(17)(18)(19) have shown that washing in water alone had a variable and unpredictable effect on spacer electrostatic charge. That in vivo effects of static charge may not support the in vitro results has been further demonstrated in a recent crossover study in 90 young children with asthma (21).…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Os inaladores dosimetrados podem ser utilizados eficientemente em todas as idades, durante a respiração normal, desde que acoplados a um espaçador [5][6][7] , e permitem ministração rápida da medicação, sendo assim melhor tolerados por crianças pequenas; além disso, em torno de 20% das partículas geradas atingem as vias aéreas inferiores 5,[8][9][10][11][12] , com padrão de deposição mais previsível e menos variável que os nebulizadores. Apesar dessas vantagens, os inaladores dosimetrados com espaçadores ainda não substituíram os nebulizadores na maioria dos serviços de emergência e hospitais pediátricos.…”

Section: Introductionunclassified

Inalador dosimetrado com espaçador artesanal versus nebulizador no tratamento da crise de sibilância na criança

Vilarinho¹,

Mendes²,

Souza³

2003

J. Pediatr. (Rio J.)

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ResumoObjetivo: Realizou-se um ensaio clínico objetivando comparar duas modalidades de administração de salbutamol na crise de sibilância em crianças -através de nebulizador de jato e através de inalador dosimetrado acoplado a um espaçador artesanal.Material e métodos: Foi estudada uma amostra de conveniência de crianças em crise moderada de sibilância, alocadas aleatoriamente em dois grupos de tratamento, de acordo com o dispositivo inalatório utilizado para a administração de salbutamol (nebulizador -grupo NEB, ou inalador dosimetrado com espaçador -grupo IDE). Os parâmetros utilizados para comparação entre os grupos foram agrupados em tabela de pontos e consistiram em sinais clínicos habitualmente usados na avaliação da gravidade da crise asmática (nível de consciência, coloração da pele, intensidade da dispnéia, intensidade da tiragem, tempo expiratório, entrada de ar e sibilância) e a saturação transcutânea de oxigênio, obtidos antes do tratamento e 15 minutos após cada administração do salbutamol. Como dados adicionais, mediram-se os tempos de preparo e de uso das medicações, computaram-se os custos envolvidos nas duas formas de tratamento, e interrogaram-se os acompanhantes sobre o grau de satisfação em relação aos tratamentos. Cada criança usou salbutamol em doses repetidas a cada 20 minutos, interrompendo-se a administração quando a crise passava de moderada a leve. Quando a crise persistia moderada, após a segunda dose de salbutamol, acrescentava-se corticóide oral. A participação das crianças era concluída quando elas passavam à crise leve, ou após a terceira dose de salbutamol. A dose de salbutamol usada no grupo IDE foi 1/3 da dose usada no grupo NEB.Resultados: Participaram do estudo 54 crianças com idades que variaram de 22 dias a 11,7 anos. Cada grupo abrangeu 27 crianças. Os grupos não diferiram demograficamente e em relação à pontuação clínica e aos valores de oximetria. A comparação dos parâmetros clínicos e de saturação de oxigênio, entre os grupos, não mostrou diferença significativa após as doses de salbutamol, havendo equivalência clínica entre doses diferentes (três vezes menor no grupo IDE, em relação ao grupo NEB); os tempos de preparo e administração da medicação e o custo do tratamento foram significativamente menores no grupo IDE. O grau de satisfação das famílias foi semelhante nos dois grupos.Conclusão: O inalador dosimetrado com espaçador artesanal pode ser utilizado na administração de salbutamol a crianças em crise de sibilância, com algumas vantagens em relação ao nebulizador. AbstractObjective: To compare the effectiveness of salbutamol administration by metered-dose inhaler with a home-made spacer versus jet nebulizer in children with moderate wheezing attacks.

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“…[11][12][13] In addition, selection of spacer design may also be unimportant for drug delivery to the periphery of the lung. 8,14 Dubus et al showed salbutamol (albuterol) responses were not significantly different between spacer devices when an HFA134a formulation was used. 11 It has also been shown that use of a spacer with or without an HFA formulation did not change the plasma profiles of beclomethasone dipropionate.…”

Section: Introductionmentioning

confidence: 99%

“…8 Similarly, a study comparing a HFA134a formulation in either the Aerochamber or the Nebuhaler spacer devices showed FPDs were equivalent with either design. 14 In addition, it has recently been reported that solution pMDIs containing HFA134a have multimodal particle size distributions. 15 Two dominating particle size modes were located at around 1 µm and 10 µm or above.…”

Section: Introductionmentioning

confidence: 99%

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

Smyth¹,

Beck²,

Williams³

et al. 2004

AAPS PharmSciTech

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INTRODUCTIONThe purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2,-tetrafluoroethane] propellant. Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber, and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI). Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at ~0.5 µm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately 0 when spacer devices were used with either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (~25% of emitted dose compared with 69%, respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance. This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly lowered sampling inlet deposition when no spacer was used.Pressurized metered dose inhalers (pMDIs) have proved an effective means of administering drugs to respiratory tract in the treatment and management of asthma. 1 However, reproducibility of dosing has been a concern with these devices because of noncompliance in prescribed usage. 2 Accurate dosing is especially necessary in cases where immediate pharmacodynamic feedback is not useful for dosage regulation, as in the case for corticosteroids employed for longterm maintenance therapy for asthma. Dose-related systemic side effects occur secondary to absorption of drug from mouth, throat, gastrointestinal tract, and lungs. Variability in dosing may result in too much or, more significantly, too little drug being delivered, with consequences for disease management. Noncompliant use of pMDIs is associated with the difficulty of inhalation-actuation coordination (particularly for children and elderly users). 3 As a consequence, devices such as spacers have been developed for use with pMDIs to improve dosing reproducibility and reduce unwanted oral deposition of aerosol droplets. 4 Spacers function by reducing the aerosol velocity, allowing time for evaporation and sedimentation, thus reducing deposition of large particles in the mouth and throat. 4 Additionally, it has been shown that spacers increase the fine particle dose (FPD) t...

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In vitro comparison of the amount of salbutamol available for inhalation from different formulations used with different spacer devices

Cited by 70 publications

References 13 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

Inalador dosimetrado com espaçador artesanal versus nebulizador no tratamento da crise de sibilância na criança

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

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