title: Novel sustained release microspheres for pulmonary drug delivery.
abstract: A novel process for generating sustained release (SR) particles for pulmonary drug delivery is described. High purity nanoparticles of a hydrophilic, ionised drug are entrapped within hydrophobic microspheres using a spray-drying approach. Sustained release of the model drug, terbutaline sulphate (TS), from the microspheres was found to be proportional to drug loading and phospholipid content. Microspheres with a 33% drug loading exhibited sustained release of 32.7% over 180 min in phosphate buffer. Release was not significantly different in simulated lung fluids. No significant burst release was observed which suggested that nanoparticles were coated effectively during spray-drying. The absence of nanoparticles at the microsphere surface was confirmed with confocal microscopy. The sustained release microspheres were formulated as a carrier-free dry powder for inhalation, and exhibited a favourable Fine Particle Fraction (FPF) of 46.5+/-1.8% and Mass Median Aerodynamic Diameter (MMAD) of 3.93+/-0.12 microm.
authors.affiliation: Department of Pharmaceutics, University of London School of Pharmacy, 29/39 Brunswick Square, London, WC1N 1AX, UK. rcook@mappharma.com
authors.forename: Robert O
authors.initials: RO
authors.lastname: Cook
authors.forename: Rupi K
authors.initials: RK
authors.lastname: Pannu
authors.forename: Ian W
authors.initials: IW
authors.lastname: Kellaway
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000336:Aerosols; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008863:Microspheres; D008954:Models, Biological; D049329:Nanostructures; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013499:Surface Properties; D013726:Terbutaline / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000336:Aerosols; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011208:Powders; D015060:1,2-Dipalmitoylphosphatidylcholine; D013726:Terbutaline