Excipient-free nanoporous microparticles of budesonide for pulmonary delivery.
The aim of this study was to investigate the application of a spray-drying process for the production of nanoporous microparticles (NPMPs) to budesonide, and to characterise the particles produced in terms of their suitability for pulmonary delivery. Budesonide was spray dried with and without ammonium carbonate from ethanol/water or methanol/water solutions. The solid-state characteristics and micromeritic (particle size, density, surface area) properties of spray dried powders were assessed. In vitro deposition studies were performed to assess aerosol performance. The densities of the NPMPs were significantly lower and the surface areas significantly higher than for non-porous spray dried or micronised material. NPMPs of budesonide demonstrated improved aerosolisation properties compared to spray dried non-porous, micronised material and two budesonide commercial products. All spray dried materials were amorphous in nature. The glass transition temperature (approximately 90 degrees C) was sufficiently high to suggest good physical stability at room temperature. When stored at 25 degrees C/60% RH NPMPs showed a reduced tendency to recrystallise compared to the equivalent non-porous spray dried powder. The physical stability and amorphous nature of NPMPs was retained, under these storage conditions for at least one year and the in vitro aerosolisation properties were not affected by the storage conditions. Excipient-free porous microparticles, prepared by the novel process described, show good potential for drug delivery by oral inhalation with improved in vitro deposition properties compared to non-porous particles.
Nolan
Lorraine M
LM
School of Pharmacy and Pharmaceutical Sciences, Trinity College, University of Dublin, Dublin 2, Ireland.
Tajber
Lidia
L
McDonald
Bernard F
BF
Barham
Ahmad S
AS
Corrigan
Owen I
OI
Healy
Anne Marie
AM
D000280:Administration, Inhalation; D000336:Aerosols; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002254:Carbonates / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D016062:Porosity; D033362:Powder Diffraction; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D014018:Tissue Distribution
D000336:Aerosols; D002254:Carbonates; D004337:Drug Carriers; D005079:Excipients; D012996:Solutions; D012997:Solvents; D019819:Budesonide; D007785:Lactose; C040502:ammonium carbonate