PMID- 12433452
OWN - NLM
STAT- MEDLINE
DCOM- 20030520
LR  - 20190910
IS  - 0378-5173 (Print)
IS  - 0378-5173 (Linking)
VI  - 249
IP  - 1-2
DP  - 2002 Dec 5
TI  - Equivalence testing of salbutamol dry powder inhalers: in vitro impaction results 
      versus in vivo efficacy.
PG  - 247-55
AB  - The aim of the study was to evaluate several impactors for in vitro equivalence 
      testing of salbutamol with respect to efficacy and to define in vitro equivalence 
      limits validated with in vivo efficacy data. The four impactors described in 
      Supplement 2000 of the European Pharmacopoeia were used: Glass Impinger (GI), 
      Metal Impinger (MI), Multistage Liquid Impinger (MSLI) and Andersen Cascade 
      Impactor (ACI). Three salbutamol dry powder formulations with different fine 
      particle doses (FPDs) were prepared and the aerodynamic particle size 
      distribution was measured. For each impactor also the recovery was determined. 
      The same three preparations were administered to 12 asthmatic patients in a 
      randomized, placebo-controlled, four-way crossover study. Cumulative doses from 
      50 microg up to 400 microg were given. The FEV(1) was measured at baseline and 15 
      min after each dose. The in vitro results showed large differences between the 
      FPDs of the three preparations with all impactors, whereas only small differences 
      were observed between the four impactors. Since the recoveries of the MI and GI 
      were low, in vitro equivalence testing should only be performed with the MSLI or 
      ACI. The in vivo measurements did not show significant differences in efficacy 
      between the three active preparations, even at the most discriminatory dose of 50 
      microg. It is concluded that in case there are no relevant differences between 
      delivered dose, inhalation device and excipients, for salbutamol dry powder 
      inhalers equivalence can be assumed when the 90% confidence interval for the FPD 
      ratio of the test product and reference product is within 0.50-1.20 and each of 
      the two products has a FPD (particles <6 microm) of at least 10 microg.
FAU - Weda, M
AU  - Weda M
AD  - National Institute for Public Health and the Environment, Laboratory for Quality 
      Control of Medicines, Postbak 40, P O Box 1, 3720 BA, Bilthoven, The Netherlands. 
      marjolein.weda@rivm.nl
FAU - Zanen, P
AU  - Zanen P
FAU - de Boer, A H
AU  - de Boer AH
FAU - Gjaltema, D
AU  - Gjaltema D
FAU - Ajaoud, A
AU  - Ajaoud A
FAU - Barends, D M
AU  - Barends DM
FAU - Frijlink, H W
AU  - Frijlink HW
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Powders)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
MH  - Adult
MH  - Albuterol/administration & dosage/*chemistry/*pharmacokinetics
MH  - Confidence Intervals
MH  - Cross-Over Studies
MH  - Humans
MH  - Middle Aged
MH  - *Nebulizers and Vaporizers
MH  - Powders
MH  - Therapeutic Equivalency
EDAT- 2002/11/16 04:00
MHDA- 2003/05/21 05:00
CRDT- 2002/11/16 04:00
PHST- 2002/11/16 04:00 [pubmed]
PHST- 2003/05/21 05:00 [medline]
PHST- 2002/11/16 04:00 [entrez]
AID - S0378517302005331 [pii]
AID - 10.1016/s0378-5173(02)00533-1 [doi]
PST - ppublish
SO  - Int J Pharm. 2002 Dec 5;249(1-2):247-55. doi: 10.1016/s0378-5173(02)00533-1.