title: Coated particle assemblies for the concomitant pulmonary administration of budesonide and salbutamol sulphate.
abstract: The aims were to prepare stable and well-dispersible pulmonary fine powders composed of combination drugs with different water solubility, to facilitate concomitant release of corticosteroid budesonide and short acting β-agonist salbutamol sulphate and to improve the dissolution of the budesonide. The budesonide nanosuspensions were prepared by a wet milling which were mixed then with salbutamol sulphate, mannitol (bulking material) and leucine (coating material) for the preparation of micron-sized particles by an aerosol flow reactor wherein leucine formed a rough coating layer on particle surface. The stable and intact particle assemblies showed excellent aerosolization performance. The emitted doses from the inhaler, Easyhaler(®), were ~3 mg/dose with a coefficient variation of 0.1, and the fine particle fractions were ~50%. Complete dissolution of budesonide nanocrystals from the particles took place within 20 min with the same rate as salbutamol sulphate. Combining the two formulation technologies enabled the encapsulation of drugs with different solubility into a single, intact particle. The leucine coating provided excellent aerosolization properties which allowed fine powder delivery from the inhaler without carrier particles. This study showed the feasibility of preparing powders for combination therapy that are utilized, for instance, in inhalation therapy.
authors.affiliation: Department of Applied Physics, Aalto University School of Science, P.O. Box 15100, 00076 Aalto, Finland. janne.raula@aalto.fi
authors.forename: Janne
authors.initials: J
authors.lastname: Raula
authors.forename: Antti
authors.initials: A
authors.lastname: Rahikkala
authors.forename: Tuomas
authors.initials: T
authors.lastname: Halkola
authors.forename: Jenni
authors.initials: J
authors.lastname: Pessi
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.forename: Esko I
authors.initials: EI
authors.lastname: Kauppinen
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D012995:Solubility; D013997:Time Factors
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004338:Drug Combinations; D005079:Excipients; D005938:Glucocorticoids; D008353:Mannitol; D019819:Budesonide; D007930:Leucine; D000420:Albuterol