Modeling and Understanding Combination pMDI Formulations with Both Dissolved and Suspended Drugs

Stephen W. Stein, Poonam Sheth, Usir S. Younis, Erik Mogalian, Paul B Myrdal

Research output: Contribution to journalArticle

2 Scopus citations

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<sup>2</sup> 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.

Original languageEnglish (US)
Pages (from-to)3455-3467
Number of pages13
JournalMolecular Pharmaceutics
Volume12
Issue number9
DOIs
StatePublished - Sep 8 2015

Keywords

  • aerodynamic particle size distribution (APSD)
  • cascade impactor
  • pressurized metered dose inhalers (pMDIs)
  • simulation model
  • suspension formulations

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

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