Pulmonary deposition of a budesonide/γ-cyclodextrin complex in vitro

• Published in: Journal of controlled release 2003-06, Vol.90 (2), p.197-205
• Main Authors: Kinnarinen, Tarja, Jarho, Pekka, Järvinen, Kristiina, Järvinen, Tomi
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Budesonide; Budesonide - administration & dosage; Budesonide - chemical synthesis; Chemistry, Pharmaceutical; Cyclodextrin complex; Cyclodextrins - administration & dosage; Cyclodextrins - chemical synthesis; gamma-Cyclodextrins; General pharmacology; Inhalation powder; Medical sciences; Multi-dose inhaler; Nebulizers and Vaporizers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pulmonary deposition
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(03)00176-7

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/γ-CD complexes. Inhalation powders containing either budesonide/γ-CD complexes (15 μg/dose; complex:carrier ratio 1:15) or budesonide (10 μg/dose and 100 μg/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/γ-CD complexes were determined initially and after 1 month’s storage (40 °C, 75% RH) using an Andersen cascade impactor. The respirable fraction (RF) of the budesonide/γ-CD complex was 35% initially and 31% after storage. The RF of budesonide was 35% (10 μg/dose) and 45% (100 μg/dose) initially, and 31% (10 μg/dose) and 51% (100 μg/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.