title: Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate.
abstract: Interactions between particles are dependent on the physicochemical characteristics of the interacting particles but it is also important to consider the manufacturing process. Blending active pharmaceutical ingredient (API) with carrier is a critical stage that determines the blend homogeneity and is the first step towards obtaining the final quality of the powder blend. The aim of this work was to study parameters that influence the interactions between API and carrier in adhesive mixtures used in DPI and their effect on API dispersion. The study was done with fluticasone propionate blended with lactose 'Lactohale 200'. The study was based on the influence of the operating conditions (speed, mixing time, resting steps during mixing), the size of the carrier and the storage conditions on the blend properties and on the API dispersion. The quality of the blends was examined by analysing the API content uniformity. Adhesion characteristics were evaluated by submitting mixtures to a sieving action by air depression with the Alpine air-jet sieve. Aerodynamic evaluation of fine particle fraction (FPF) was obtained using a Twin Stage Impinger; the FPF being defined as the mass percentage of API below 6.4 μm. For good dispersion and therefore good homogeneity of the API in the carrier particles, speed and powder blending time have to be sufficient, but not too long to prevent the appearance of static electricity, which is not favourable to homogeneity and stability. The FPF increases with the decrease in the carrier size. The storage conditions have also to be taken into consideration. Higher humidity favours the adhesion of API on the carrier and decreases the FPF.
authors.affiliation: College of Pharmacy, U 1008, Univ. Lille Nord de France, 3, Rue du Professeur Laguesse, BP 83, 59006, Lille, France.
authors.forename: V N P
authors.initials: VN
authors.lastname: Le
authors.forename: T H
authors.initials: TH
authors.lastname: Hoang Thi
authors.forename: E
authors.initials: E
authors.lastname: Robins
authors.forename: M P
authors.initials: MP
authors.lastname: Flament
mesh_terms: D000268:Adhesiveness; D000280:Administration, Inhalation; D000336:Aerosols; D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004356:Drug Storage; D058995:Dry Powder Inhalers; D000068298:Fluticasone; D006813:Humidity; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000336:Aerosols; D000730:Androstadienes; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D014867:Water; D000068298:Fluticasone; D007785:Lactose