Pharmacoscintigraphic evaluation of lipid dry powder budesonide formulations for inhalation.
Lung deposition of new formulations of budesonide, using solid lipid microparticles (SLmP) as a pharmaceutically acceptable filler and carrier for inhalation aerosols, and administered from a dry powder inhaler (Cyclohaler), were compared with that from Pulmicort Turbuhaler. Six healthy volunteers took part in a three-way randomized cross-over study, and inhaled a nominal dose of 400 microg budesonide, labelled with 99mTc, on each study day. Lung deposition was determined by gamma scintigraphy and by a pharmacokinetic method. The percentage of dose (SD) in the whole lung was 49.9 (3.7)% for the lipidic matricial form (M) and 62.8 (4.9)% for the lipidic physical blend formulation (PB). These results corresponded well with the in vitro fine particle assessment. In comparison with data recorded in literature for in vivo deposition obtained with Pulmicort Turbuhaler, it was estimated that lung deposition was 1.5 and 2.0 times higher for the M and PB formulations, respectively. Furthermore, the relative drug availability obtained from the pharmacokinetic evaluation, expressed as the percentage of pulmonary absorption of the comparator product, was 154% and 220% for M and PB, respectively. The results of the present study indicate that pulmonary administration using SLmP gives a prominent and significant increase in budesonide lung deposition.
Sebti
Thami
T
Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Brussels, Belgium.
Pilcer
Gabrielle
G
Van Gansbeke
Bernard
B
Goldman
Serge
S
Michils
Alain
A
Vanderbist
Francis
F
Amighi
Karim
K
D000042:Absorption; D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000737:chemistry*; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D006801:Humans; D001239:Inhalation; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000473:pathology; D008297:Male; D009330:Nebulizers and Vaporizers; D011208:Powders; D011877:Radionuclide Imaging / Q000379:methods*; D012129:Respiratory Function Tests; D013678:Technology, Pharmaceutical / Q000379:methods
D001993:Bronchodilator Agents; D008055:Lipids; D011208:Powders; D019819:Budesonide