VALIDATING PARTICLE SIZE AND MASS CONCENTRATION OF MICRONIZED FLUTICASONE PROPIONATE DELIVERED AS MONODISPERSE AEROSOLS

• Published in: Journal of aerosol medicine and pulmonary drug delivery Vol. 24; no. 6; p. 323
• Main Authors: Kalsi, H S, Biddiscombe, M F, Usmani, O S
• Format: Journal Article
• Language: English
• Published: 01.12.2011
• Subjects: Aerosol generators; Aerosol particles; Chromatography; Particle size distribution; Regression analysis
• ISSN: 1941-2711

Aerosol particle size is a major issue for targeting therapeutic drugs via the inhalation route. Existing devices for delivering inhaled drugs produce polydisperse aerosols. Monodisperse aerosols are designed to deliver a drug mass with a narrow particle size distribution and can be used to target therapy. We developed 3 monodisperse aerosols with MMAD's of 1.5, 3, and 6 mu m from fluticasone propionate (FP) using a spinning-top aerosol generator. Aerodynamic Particle Sizer's (APS) can measure particle MMAD and mass concentration in near real time but assume that particles are spherical with uniform density. Validation tests of APS measurements were warranted before in vivo experimentation. For validation of APS particle MMAD aerosols were sampled by an Andersen Cascade Impactor (ACI) at a flow rate of 28 L/min for 2 minutes and MMAD was determined by high-liquid performance chromatography (HPLC). For validation of APS particle mass concentration aerosols were drawn through total trap filters using a 2 L volume syringe and concentration mass from filters was determined by HPLC. Regression analysis showed a linear relationship between methods for particle MMAD (r super(2) = 0.98) and for mass concentration for the 3 monodisperse aerosols, 1.5 (r super(2) = 0.88), 3 (r super(2) = 0.89), and 6 MMAD (r super(2) = 0.92). Although there was not a one to one correspondence between the two methods for measuring mass concentration this can be resolved by appropriate correction factors. The APS can therefore be used to measure both particles size and mass concentration of a given monodisperse FP distribution.