pulmicort and gamma-cyclodextrin

The present study describes the crystal structure changes of gamma-cyclodextrin (gamma-CD) during the solution enhanced dispersion by supercritical fluids (SEDS) process and its effect on dissolution behaviour of complexed budesonide.. gamma-CD solution (10 mg/ml in 50% ethanol) was pumped together with supercritical carbon dioxide through a coaxial nozzle with or without a model drug, budesonide (3.3 mg/ml). The processing conditions were 100 b and 40, 60 or 80 degrees C. gamma-CD powders were characterised before and after vacuum-drying (2-3 days at RT) with XRPD, SEM and NMR. Budesonide/gamma-CD complexation was confirmed with DSC and XRPD. The dissolution behaviour of complexed budesonide was determined in aqueous solution (1% gamma-CD, 37 degrees C, 100 rpm).. During the SEDS process (100 b, 40 and 60 degrees C), gamma-CD and budesonide/gamma-CD complexes crystallized in a tetragonal channel-type form. The vacuum-drying transformed crystalline gamma-CD into amorphous form while the complexes underwent a tetragonal-to-hexagonal phase transition. The increase in the processing temperature decreased the crystallinity of gamma-CD. At 80 degrees C, amorphous gamma-CD was obtained while the complexes crystallized in a hexagonal channel-type form. The dissolution behaviour of budesonide/gamma-CD complexes was dependent on their crystal structure: the tetragonal form dissolved faster than the hexagonal form.. The crystal structure of gamma-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.

Topics: Budesonide; Carbon Dioxide; Crystallography, X-Ray; gamma-Cyclodextrins; Microscopy, Electron, Scanning; Molecular Structure; Solubility

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.

Topics: Administration, Inhalation; Budesonide; Chemistry, Pharmaceutical; Cyclodextrins; gamma-Cyclodextrins; Nebulizers and Vaporizers; Particle Size