Cyclodextrins as a potential carrier in drug nebulization.
The inhalation route is widely studied for many drug applications focusing on either local or systemic distributions. One matter of concern is the solubilization of hydrophobic drugs. We have studied the feasibility of using different cyclodextrins (CDs) to elaborate pharmaceutical formulations for the inhalation route and tested the short-term toxicity of such formulations administered by inhalation to C57BL/6 mice. We have shown that HP-beta-CD, gamma-CD, as well as RAMEB aqueous solutions can undergo aerosolization and that the resulting droplet-size ranges are compatible with pulmonary deposition. In vivo, we have demonstrated that short-term exposure to inhaled HP-beta-CD, gamma-CD and RAMEB solutions are non-toxic after assessing bronchoalveolar lavage (BAL), lung and kidney histology, bronchial responsiveness to methacholine and blood urea. The only change noted is a slight increase in lymphocyte count in the BAL after HP-beta-CD and gamma-CD inhalation. We conclude that CDs are useful in significantly enhancing the solubility of apolar drugs with a view to inhalation therapy although an increase in lymphocyte counts in the BAL after CDs inhalations needs further investigations.
Evrard
B
B
Department of Pharmacy, University of Liège, CHU-Tour 4, Bât B36, Avenue de l' Hôpital 1, 4000, Liège 1, Belgium. B.Evrad@ulg.ac.be
Bertholet
P
P
Gueders
M
M
Flament
M-P
MP
Piel
G
G
Delattre
L
L
Gayot
A
A
Leterme
P
P
Foidart
J-M
JM
Cataldo
D
D
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001806:Blood Urea Nitrogen; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003505:Cyclodextrins / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009330:Nebulizers and Vaporizers; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D013500:Surface Tension; D014783:Viscosity; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000633:toxicity; D047408:gamma-Cyclodextrins / Q000737:chemistry / Q000633:toxicity
D000336:Aerosols; D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D004364:Pharmaceutical Preparations; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins