Hollow porous particles in metered dose inhalers

• Published in: Pharmaceutical research Vol. 17; no. 2; pp. 168 - 174
• Main Authors: DELLAMARY, L. A, TARARA, T. E, SMITH, D. J, WOELK, C. H, ADRACTAS, A, COSTELLO, M. L, GILL, H, WEERS, J. G
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.02.2000; Springer Nature B.V
• Subjects: Administration, Inhalation; Aerosols; Albuterol - administration & dosage; Albuterol - pharmacokinetics; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - pharmacokinetics; Asthma - drug therapy; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - pharmacokinetics; Cromolyn Sodium - administration & dosage; Cromolyn Sodium - pharmacokinetics; Ethanolamines - administration & dosage; Ethanolamines - pharmacokinetics; Formoterol Fumarate; General pharmacology; Humans; In Vitro Techniques; Lung; Medical sciences; Microscopy, Electron; Microspheres; Nebulizers and Vaporizers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powders; Respiratory system; Particle size; Microsphere; Stability; Pharmaceutical technology; Respiratory disease; Spray drying; Suspension; Drug carrier; Propellant fluid; Powder; Asthma; Dosage form; Inhaler; Obstructive pulmonary disease; Aerosol batcher; Physicochemical properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1007513213292

To assess the physical stability and aerosol characteristics of suspensions of hollow porous microspheres (PulmoSpheres) in HFA-134a. Cromolyn sodium, albuterol sulfate, and formoterol fumarate microspheres were prepared by a spray-drying method. Particle size and morphology were determined via electron microscopy. Particle aggregation and suspension creaming times were assessed visually, and aerosol performance was determined via Andersen cascade impaction and dose uniformity studies. The hollow porous particle morphology allows the propellant to permeate freely within the particles creating a novel form of suspension termed a homodispersion, wherein the dispersed and continuous phases are identical, separated by an insoluble interfacial layer of drug and excipient. Homodispersion formation improves suspension stability by minimizing the difference in density between the particles and the medium, and by reducing attractive forces between particles. The improved physical stability leads to excellent dose uniformity. Excellent aerosolization efficiencies are also observed with PulmoSpheres formulations, with fine particle fractions of about 70%. The formation of hollow porous particles provides a new formulation technology for stabilizing suspensions of drugs in hydrofluoroalkane propellants with improved physical stability, content uniformity, and aerosolization efficiency.