title: Modeling and Understanding Combination pMDI Formulations with Both Dissolved and Suspended Drugs.
abstract: A simulation model has been established to predict the residual aerodynamic particle size distribution (APSD) of dual-component pressurized metered dose inhalers (pMDIs). More specifically, this model estimates the APSD of pMDI formulations containing dissolved and suspended compounds for various formulations, and has been verified experimentally. Simulated and experimental data illustrate that APSDs of the dissolved and suspended components of the pMDI are influenced by concentrations of the dissolved and micronized suspended drugs, along with suspended drug size. Atomized droplets from such combination formulations may contain varying number of suspended drug particles and a representative concentration of dissolved drug. These sub-populations of atomized droplets may explain the residual APSDs. The suspended drug follows a monomodal, lognormal distribution and is more greatly impacted by the size and concentration of the suspended drug in comparison to the concentration of dissolved drug. On the other hand, dissolved drug illustrates a bimodal, lognormal residual particle size distribution both theoretically and experimentally. The smaller mode consists of residual particles made of dissolved drug only, while the larger mode consists of residual particles that contain both dissolved and suspended drugs. The model effectively predicted the size distributions of both the dissolved and suspended components of combination formulations (r(2) value of 0.914 for the comparison of simulated versus experimental MMAD values for the formulations examined). The results demonstrate that this model is a useful tool that may be able to expedite the development of combination pMDI formulation.
authors.affiliation: 3M Drug Delivery Systems , 3M Center-Building 260-3A-05, St. Paul, Minnesota 55144, United States.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Stein
authors.affiliation: Cirrus Pharmaceuticals, Inc. , 511 Davis Drive, Suite 100, PO Box 14748, Morrisville, North Carolina 27560, United States.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sheth
authors.affiliation: College of Pharmacy, The University of Arizona , 1703 East Mabel Street, PO Box 210207, Tucson, Arizona 85721, United States.
authors.forename: Usir S
authors.initials: US
authors.lastname: Younis
authors.affiliation: Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
authors.forename: Erik
authors.initials: E
authors.lastname: Mogalian
authors.affiliation: College of Pharmacy, The University of Arizona , 1703 East Mabel Street, PO Box 210207, Tucson, Arizona 85721, United States.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Myrdal
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D001993:Bronchodilator Agents / Q000737:chemistry*; D003198:Computer Simulation; D004867:Equipment Design; D036501:Metered Dose Inhalers; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011312:Pressure; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000336:Aerosols; D001993:Bronchodilator Agents; D004364:Pharmaceutical Preparations
keywords: aerodynamic particle size distribution (APSD); cascade impactor; pressurized metered dose inhalers (pMDIs); simulation model; suspension formulations