title: Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation.
abstract: The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters. The effect of drug/lactose co-micronization on aerosolization was then evaluated. In vitro deposition studies were performed with the twin stage glass impinger and the inhaler Spinhaler. Micronization did not induce DSC-detectable amorphization and gave a highly cohesive, poor flowable powder with a theoretical aerodynamic diameter of 5 microm. The powder was then blended with coarse lactose and optionally fine lactose. Unfortunately, the respirable fraction could not be optimized and remained below 10%. On the other hand, a co-micronized powder drug/fine lactose 50:50 gave a respirable fraction of 16%. Following blending with a carrier, the respirable fraction and the emitted dose fraction reached 23% and 69%, respectively. The use of a fine lactose grade for co-micronization was essential. In conclusion, this study demonstrated that co-micronization with a fine lactose is an efficient and simple strategy to formulate a powder for inhalation with enhanced aerosolization properties, especially for highly cohesive drug substance.
authors.affiliation: Technologie Servier, 25/27 Rue Eugène Vignat, 45000 Orléans, France.
authors.forename: K
authors.initials: K
authors.lastname: Giry
authors.forename: J M
authors.initials: JM
authors.lastname: Péan
authors.forename: L
authors.initials: L
authors.lastname: Giraud
authors.forename: S
authors.initials: S
authors.lastname: Marsas
authors.forename: H
authors.initials: H
authors.lastname: Rolland
authors.forename: P
authors.initials: P
authors.lastname: Wüthrich
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D007785:Lactose / Q000008:administration & dosage*; D011208:Powders; D013678:Technology, Pharmaceutical
chemical_list: D000336:Aerosols; D011208:Powders; D007785:Lactose