Methacholine dry powder inhaler as a new tool for bronchial challenge test.
BACKGROUND
The methacholine (MCH) challenge test is performed to detect bronchial hyperresponsiveness in subjects suffering from asthma. It is conducted by inhaling spasmogen substances at increasing doses and measuring FEV1-PD20 variation following the bronchoconstriction evoked.


OBJECTIVE
This paper describes a new method for MCH challenge test using pre-metered respirable powders of MCH at different doses for facilitating test execution. The availability of a series of pre-metered doses gives higher control over aerosolized dose and fine particle fraction (respirable dose), improving the accuracy and repeatability of the test. Dosimetric tests with MCH solution and pre-dosed powder challenge tests were clinically compared.


METHODS
The inhalation powders were prepared by spray drying of solutions of methacholine, mannitol and hydroxypropylmethylcellulose in which different concentrations of MCH were included. The methacholine powders prepared were carefully characterized in terms of aerodynamic properties.


RESULTS
Inhalation powders containing methacholine from 12.5 to 200 microg per metered dose, having a fine particle fraction between 40 and 60%, were prepared using mannitol and cellulose polymer. Eighteen subjects (12 hyperresponsive and six normal) were subjected to both the MCH solution and powder tests in random sequence. No significant differences in FEV1 and PD20 values were found between the challenge tests performed with liquid and powder formulations of methacholine.


CONCLUSIONS
Powders of MCH having high respirability of the delivered doses can be prepared by spray drying. They allow for the performance of a challenge test using a dry powder inhaler. The powder dose series can be an alternative to the current dosimetric test with MCH solutions.
Department of Pharmaceutical Sciences, University of Ferrara (I-Ferrara), Italy.
G
G
Colombo
C
C
Terzano
P
P
Colombo
A
A
Petroianni
A
A
Ricci
F
F
Buttini
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D016535:Bronchial Hyperreactivity / Q000175:diagnosis* / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000295:instrumentation*; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004867:Equipment Design; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008353:Mannitol / Q000737:chemistry; D036501:Metered Dose Inhalers; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D010316:Particle Size; D011208:Powders; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods
D000336:Aerosols; D016085:Bronchoconstrictor Agents; D011208:Powders; D016210:Methacholine Chloride; D065347:Hypromellose Derivatives; D008353:Mannitol; D008747:Methylcellulose