PURPOSE: To develop a unique in vitro aqueous fluid-capacity-limited dissolution system for the kinetic assessment of respirable aerosol drug particles from inhaler products. METHODS: Aerosol particles of 5 inhaled corticosteroids (ICSs) from 7 inhaler products were collected in the aerodynamic 2.1-3.3 or 4.7-5.8 mum on the filter membranes using the Andersen cascade impactor. Each filter membrane was then placed onto the donor compartment of the Transwell(R) system, where addition of 0.04ml aqueous fluid initiated aerosol ICS dissolution and permeation across its supporting membrane at 37 degrees C and approximately 100% humidity. RESULTS: The % profiles of dissolution and permeation were apparent first-order or pseudo-zero-order, reaching varying 1.9-95.0% by 5 h. Their kinetics overall conformed to the ICS aqueous solubility. With increasing aerosol mass, however, the profiles decelerated, attributed to undissolved ICSs left by the limited dissolution fluid capacity. The profiles could be also product-specific, as beclomethasone dipropionate aerosols from QVAR dissolved faster than those from VANCERIL, whereas fluticasone propionate aerosols from two different inhaler products exhibited comparable profiles. The 2.1-3.3 mum aerosols dissolved faster than the 4.7-5.8 mum aerosols. CONCLUSIONS: Aerosol ICS dissolution into the limited aqueous fluid volume differed kinetically due to ICS solubility and aerosol mass, size, formulation and/or generation.
PURPOSE: To develop a unique in vitro aqueous fluid-capacity-limited dissolution system for the kinetic assessment of respirable aerosol drug particles from inhaler products. METHODS: Aerosol particles of 5 inhaled corticosteroids (ICSs) from 7 inhaler products were collected in the aerodynamic 2.1-3.3 or 4.7-5.8 mum on the filter membranes using the Andersen cascade impactor. Each filter membrane was then placed onto the donor compartment of the Transwell(R) system, where addition of 0.04ml aqueous fluid initiated aerosol ICS dissolution and permeation across its supporting membrane at 37 degrees C and approximately 100% humidity. RESULTS: The % profiles of dissolution and permeation were apparent first-order or pseudo-zero-order, reaching varying 1.9-95.0% by 5 h. Their kinetics overall conformed to the ICS aqueous solubility. With increasing aerosol mass, however, the profiles decelerated, attributed to undissolved ICSs left by the limited dissolution fluid capacity. The profiles could be also product-specific, as beclomethasone dipropionate aerosols from QVAR dissolved faster than those from VANCERIL, whereas fluticasone propionate aerosols from two different inhaler products exhibited comparable profiles. The 2.1-3.3 mum aerosols dissolved faster than the 4.7-5.8 mum aerosols. CONCLUSIONS: Aerosol ICS dissolution into the limited aqueous fluid volume differed kinetically due to ICS solubility and aerosol mass, size, formulation and/or generation.
Authors: Yuanlin Song; Wan Namkung; Dennis W Nielson; Jae-Woo Lee; Walter E Finkbeiner; A S Verkman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-10-09 Impact factor: 5.464
Authors: Cynthia K Brown; Horst Dieter Friedel; Amy R Barker; Lucinda F Buhse; Susanne Keitel; Todd L Cecil; Johannes Kraemer; J Michael Morris; Christos Reppas; Mary P Stickelmeyer; Chikako Yomota; Vinod P Shah Journal: AAPS PharmSciTech Date: 2011-06-18 Impact factor: 3.246
Authors: P Worth Longest; Karl Bass; Rabijit Dutta; Vijaya Rani; Morgan L Thomas; Ahmad El-Achwah; Michael Hindle Journal: Expert Opin Drug Deliv Date: 2018-12-10 Impact factor: 6.648