Determination of the relative bioavailability of salbutamol to the lungs following inhalation from dry powder inhaler formulations containing drug substance manufactured by supercritical fluids and micronization.
OBJECTIVE
The relative lung bioavailability of salbutamol sulfate particles produced using supercritical fluids (SEDS) and delivered by dry powder inhaler (DPI) was compared with the performance of a conventional micronized drug DPI using the same device design (Clickhaler, Innovata Biomed).


METHODS
Twelve healthy volunteers and 11 mild asthmatic patients completed separate four-way randomised cross-over studies, assessing the relative bioavailability of salbutamol sulfate (urinary excretion method), formulated as SEDS particles (three batches) and micronized particles (Asmasal inhaler, UCB Pharma Ltd). Post-treatment improvements in patient lung function were assessed by measuring FEV(1). Physicochemical evaluation of the three SEDS batches revealed inter-batch differences in particle size and shape.


RESULTS
There was no significant difference in the relative lung bioavailability of salbutamol and its bronchodilator response between the best performing SEDS formulation and the Asmasal inhaler in volunteers and patients, respectively. SEDS salbutamol sulfate showing wafer like morphology gave greater fine particle dose, relative lung bioavailability and enhanced bronchodilation compared to other SEDS batches containing elongated particles.


CONCLUSIONS
Active Pharmaceutical Ingredient (API) manufactured using supercritical fluids and delivered by DPI can provide similar lung bioavailability and clinical effect to the conventional micronized commercial product. Product performance is however notably influenced by inter-batch differences in particle characteristics.
Richardson
Catherine H
CH
Institute of Pharmaceutical Innovation, University of Bradford, Bradford, BD7 1DP, UK.
de Matas
Marcel
M
Hosker
Harold
H
Mukherjee
Rahul
R
Wong
Ian
I
Chrystyn
Henry
H
D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D009330:Nebulizers and Vaporizers; D010316:Particle Size
D000420:Albuterol