Pharmaceutical transition to non-CFC pressurized metered dose inhalers.
The production of ozone-depleting chlorofluorocarbons (CFCs) was discontinued on 1 January 1996 for all uses deemed non-essential under the Montreal Protocol. However, the use of CFCs as propellants in pressurized metered dose inhalers (pMDIs) was classed as essential, providing an exemption from the agreement. Following extensive research, the hydrofluoroalkanes (HFA) 134a and 227 were identified as the only suitable replacements for CFC propellants in pMDIs. The drug delivery of pMDIs formulated with HFA 134a as a propellant and containing either salbutamol (100 microg per actuation) or fluticasone propionate (125 and 250 microg per actuation) have been assessed for dose uniformity and particle size distribution. All of the HFA 134a pMDIs delivered doses throughout the life of the canisters that were reproducible and within specified regulatory requirements. Each of the products provided an emitted dose which was within +/- 25% of the mean value indicating accurate and consistent dosing (93, 112 and 221 microg per metered dose for the salbutamol 100 microg and fluticasone propionate 125 and 250 microg HFA 134a pMDIs, respectively). These findings were unaffected by changing the storage orientation of the pMDI or by using the device in a manner designed to simulate typical patient use. The particle size distributions of HFA 134a pMDI doses did not differ significantly from those of the corresponding CFC pMDIs. As a result of the similar pharmaceutical performance, it is unnecessary to change the label claim dose of active drug when making the transition from a CFC to an HFA 134a pMDI for salbutamol (Ventolin) and fluticasone propionate (Flixotide). A seamless transition to non-CFC pMDIs will help to maintain the confidence of patients and healthcare professionals in asthma therapy.
Glaxo Wellcome Research and Development, Inhalation Product Development, Ware, Herts, UK.
A
A
Cripps
M
M
Riebe
M
M
Schulze
R
R
Woodhouse
D000335:Aerosol Propellants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000420:Albuterol / Q000494:pharmacology; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000494:pharmacology; D000068298:Fluticasone; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009330:Nebulizers and Vaporizers / Q000592:standards*; D010316:Particle Size; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000420:Albuterol; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons