title: Dispersibility of lactose fines as compared to API in dry powders for inhalation.
abstract: This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. Fine particle assessment demonstrates that the lactose fines have higher dispersibility than the API. For standard formulations, processing time has a limited effect on the Fine Particle Fraction (FPF). For formulations containing magnesium stearate (MgSt), FPF of BDP is heavily influenced by processing time, with an initial increase, followed by a decrease at longer mixing times. An equation modeling the observed behavior is presented. Surprisingly, the dispersibility of the lactose fines present in the same formulation remains unaffected by mixing time. Magnesium analysis demonstrates that MgSt is transferred to the fine particles during the mixing process, thus lubrication both BDP and lactose fines, which leads to an increased FPF. Dry particle sizing of the formulations reveals a loss of fine particles at longer mixing times. Incorporation of fine particles into the carrier surfaces is believed to be behind this, and is hence a mechanism of importance as regards the dispersion performance of dry powders for inhalation.
authors.affiliation: Pharmaceutical Development, AstraZeneca Gothenburg, Pepparedsleden 1, 43183 Mölndal, Sweden. Electronic address: Kyrre.Thalberg@astrazeneca.com.
authors.forename: Kyrre
authors.initials: K
authors.lastname: Thalberg
authors.affiliation: Pharmaceutical Development, AstraZeneca Gothenburg, Pepparedsleden 1, 43183 Mölndal, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Åslund
authors.affiliation: Pharmaceutical Development, AstraZeneca Gothenburg, Pepparedsleden 1, 43183 Mölndal, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Skogevall
authors.affiliation: Pharmaceutical Development, AstraZeneca Gothenburg, Pepparedsleden 1, 43183 Mölndal, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Andersson
mesh_terms: D000280:Administration, Inhalation; D018927:Anti-Asthmatic Agents / Q000737:chemistry; D001507:Beclomethasone / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry*; D005938:Glucocorticoids / Q000737:chemistry; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D011208:Powders
chemical_list: D018927:Anti-Asthmatic Agents; D005079:Excipients; D005938:Glucocorticoids; D011208:Powders; D007785:Lactose; D001507:Beclomethasone
keywords: Dispersibility; Dry powder inhalation; Fine particle fraction; High shear mixing; Lactose carrier; Lactose fines