Pulmonary deposition of a budesonide/gamma-cyclodextrin complex in vitro.
Cyclodextrins (CDs) may be potential excipients in inhalation powders; e.g., to increase drug stability, dissolution rate and bioavailability, or to decrease local irritation of an inhaled drug. The aim of this study was to investigate the effect of CD complexation on the pulmonary deposition of drugs. Studies were performed by using novel Taifun multi-dose dry powder inhalers and budesonide as a model compound. A precipitation method was developed to prepare solid budesonide/gamma-CD complexes. Inhalation powders containing either budesonide/gamma-CD complexes (15 microg/dose; complex:carrier ratio 1:15) or budesonide (10 microg/dose and 100 microg/dose; drug:carrier ratio 1:159 and 1:15, respectively) with a lactose carrier, were prepared by dry mixing. The in vitro pulmonary depositions of budesonide and budesonide/gamma-CD complexes were determined initially and after 1 month's storage (40 degrees C, 75% RH) using an Andersen cascade impactor. The respirable fraction (RF) of the budesonide/gamma-CD complex was 35% initially and 31% after storage. The RF of budesonide was 35% (10 microg/dose) and 45% (100 microg/dose) initially, and 31% (10 microg/dose) and 51% (100 microg/dose) after storage, respectively. In conclusion, CDs may be used in inhalation powders to improve pharmaceutical and biopharmaceutical properties of drugs without lowering their pulmonary deposition.
Kinnarinen
Tarja
T
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
Jarho
Pekka
P
Järvinen
Kristiina
K
Järvinen
Tomi
T
D000280:Administration, Inhalation; D019819:Budesonide / Q000008:administration & dosage / Q000138:chemical synthesis*; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000008:administration & dosage / Q000138:chemical synthesis*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D047408:gamma-Cyclodextrins
D003505:Cyclodextrins; D047408:gamma-Cyclodextrins; D019819:Budesonide; C023792:gamma-cyclodextrin