Acute safety of the CFC-free propellant HFA-134a from a pressurized metered dose inhaler

Abstract

The acute safety of the alternative chlorofluorocarbon-free (CFC-free) propellant HFA-134a from a pressurized metered-dose inhaler (MDI) was assessed in 12 healthy male subjects according to a double-blind, randomized, crossover design. On each of three consecutive days, cumulative doses of 1,2,4,8 and 16 inhalations were administered 30 min apart from one of three MDIs. The three MDIs contained either the HFA-134a CFC-free system without drug (HFA-Placebo), the CFC-free system with salbutamol sulphate (HFA-Salbutamol), or a conventional CFC propellant mixture without drug (CFC-Placebo). Pulmonary function (FEV1, FEF25-75%), cardiovascular performance (heart rate and blood pressure), objective tremor measurements and serum potassium were measured after each incremental dose. Similar responses for pulmonary function, cardiovascular performance, tremor and serum potassium were observed between the HFA-Placebo and CFC-Placebo groups. No statistically significant difference was seen in change from baseline of any parameter between the two propellant systems. The administration of HFA-Salbutamol produced statistically significant dose-related increases in heart rate, systolic blood pressure and tremor and a significant dose-related decrease in serum potassium; these responses were expected based on cumulative doses of active drug. Blood samples for HFA-134a analysis were collected to measure systemic absorption of this propellant. Levels of HFA-134a between 200 and 700 ng.ml-1 were detected in all subjects given the CFC-free system. This study shows that acute inhalation of HFA-134a in a CFC-free system is as safe as a CFC propellant system. Salbutamol sulphate in the CFC-free system can be delivered in a dose-linear fashion, without any noticeable change in the safety profile of active drug.

Moving from CFC Aerosol to HFA Aerosol or Dry Powder Inhalers: What Do Patients Think?

“…Environmentally friendly alternatives to the CFC-driven inhalers have been developed [9, 10]. Nevertheless, the transition from CFC aerosol inhalers to reformulated CFC-free pMDIs carries a number of uncertainties.…”

“…Possible adverse effects on environment and health [1, 2, 3, 4]as a result of the destruction of the Earth’s ozone layer by chlorofluorocarbon (CFC) propellants [5, 6], as used in pMDIs, paved the way for the ban of these compounds under the Montreal Protocol [7, 8]. New propellants without ozone-damaging properties, hydrofluoroalkanes (HFA), have been developed, and reformulated inhalers have been shown to be non-toxic, safe and effective [9, 10, 11, 12]. However, few data exist on whether patients find the HFA-driven pMDIs acceptable [13].…”

New Delivery Systems and Propellants

“…The mass median aerodynamic diameter of Airomir is 2.69 µm versus 2.62 µm for Ventolin, but the fine particle fraction of the emitted dose as inhaled into the lung contained in particles less than 5.8 µm in diameter was greater for Airomir (65.5% versus 41.4%, P<0.05) (13,14) . The emitted doses are different, being less for Airomir than Ventolin (85.3±5.4 µg versus 96.9±6.9 µg, p.05) (13), but, because the fine particle fraction is greater for Airomir, this translates into a fine particle dose for Airomir of 54.2 µg compared with that of 40.3 µg for Ventolin.…”

“…The emitted doses are different, being less for Airomir than Ventolin (85.3±5.4 µg versus 96.9±6.9 µg, p.05) (13), but, because the fine particle fraction is greater for Airomir, this translates into a fine particle dose for Airomir of 54.2 µg compared with that of 40.3 µg for Ventolin. When Airomir was used with several spacers of different volumes, the fine particle dose was enhanced and comparable between all spacers: approximately 70 µg was measured at the mouthpiece of the Aerochamber (Trudell Medical International, London, Ontario) or Babyhaler (Glaxo Wellcome, Ware, United Kingdom) or metal Nebuchamber (Astra Pharma, Lund, Sweden) (13,14). A series of pharmcokinetic studies in normal subjects from Lipworth and co-workers (15) levels with HFA salbutamol inhaled through both plastic and metal spacers compared with either the HFA pMDI alone or salbutamol delivered through the Turbuhaler (16), supporting greater total deposition in the lung of HFA salbutamol.…”

Aerosol therapy in childhood asthma

“…A pressão no interior do cilindro é de 400 kPa. A indústria farmacêutica está pesquisando novos propelentes, não clorados e que não afetem a camada de ozônio 1,59,60 . Na mistura há também um agente tensoativo (lecitina ou ácido oléico), para evitar a coalescência das partículas da droga 1 .…”