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Pharmaceutical Research

, Volume 25, Issue 2, pp 337–348 | Cite as

An Investigation into the Dispersion Mechanisms of Ternary Dry Powder Inhaler Formulations by the Quantification of Interparticulate Forces

  • Matthew D. Jones
  • Jennifer C. Hooton
  • Michelle L. Dawson
  • Alan R. Ferrie
  • Robert Price
Research Paper

Abstract

Purpose

To investigate the dispersion mechanism(s) of ternary dry powder inhaler (DPI) formulations by comparison of the interparticulate adhesions and in vitro performance of a number of carrier–drug–fines combinations.

Materials and Methods

The relative levels of adhesion and cohesion between a lactose carrier and a number of drugs and fine excipients were quantified using the cohesion–adhesion balance (CAB) approach to atomic force microscopy. The in vitro performance of formulations produced using these materials was quantified and the particle size distribution of the aerosol clouds produced from these formulations determined by laser diffraction.

Results

Comparison between CAB ratios and formulation performance suggested that the improvement in performance brought about by the addition of fines to which the drug was more adhesive than cohesive might have been due to the formation of agglomerates of drug and fines particles. This was supported by aerosol cloud particle size data. The mechanism(s) underlying the improved performance of ternary formulations where the drug was more cohesive than adhesive to the fines was unclear.

Conclusions

The performance of ternary DPI formulations might be increased by the preferential formation of drug–fines agglomerates, which might be subject to greater deagglomeration forces during aerosolisation than smaller agglomerates, thus producing better formulation performance.

Key words

adhesion agglomeration atomic force microscope fines ternary interactive mixture 

Abbreviations

AFM

Atomic force microscopy

CAB

Cohesion–adhesion balance

CV

Coefficient of variation

DPI

Dry powder inhaler

ED

Emitted dose

FFD

Formoterol fumarate dihydrate

FP

Fluticasone propionate

FPD

Fine particle dose

FPF

Fine particle fraction

GSD

Geometric standard deviation

HPLC

High performance liquid chromatography

MMAD

Mass median aerodynamic diameter

NGI

Next Generation Impactor

Ra

Mean roughness

Rq

Root mean square roughness

SEM

Scanning electron microscope

SX

Salmeterol xinafoate

Notes

Acknowledgements

The authors gratefully acknowledge the Engineering and Physical Sciences Research Council and GlaxoSmithKline for their generous funding of this work. The authors gratefully acknowledge the assistance of Andy Smith (Sympatec Ltd.) in obtaining the aerosol cloud particle size distribution data.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Matthew D. Jones
    • 1
    • 3
  • Jennifer C. Hooton
    • 1
    • 4
  • Michelle L. Dawson
    • 2
  • Alan R. Ferrie
    • 2
  • Robert Price
    • 1
  1. 1.Pharmaceutical Surface Science Research Group, Department of Pharmacy and PharmacologyUniversity of BathBathUK
  2. 2.GlaxoSmithKline Research and DevelopmentHertsUK
  3. 3.Department of Pharmaceutics, The School of PharmacyUniversity of LondonLondonUK
  4. 4.AstraZeneca R&DCheshireUK

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