Pharmaceutical Research

, Volume 24, Issue 1, pp 125–135 | Cite as

In Vitro Investigation of Drug Particulates Interactions and Aerosol Performance of Pressurised Metered Dose Inhalers

  • Daniela Traini
  • Paul M. Young
  • Philippe Rogueda
  • Robert Price
Research Paper

Abstract

Purpose

To determine a relationship between adhesive and cohesive inter-particulate forces of interactions and in vitro performance in pressurised metered dose inhalers (pMDIs) suspension formulations.

Methods

Interparticulate forces of salbutamol sulphate (SS), budesonide (BUD) and formoterol fumarate dihydrate (FFD) were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H, 3H perfluoropentane (HPFP). Experimental data were analysed using the recently developed cohesive/adhesive analysis method (CAB) and compared with in vitro deposition performances in pMDIs systems using Andersen cascade impactor (ACI).

Results

The in vitro investigation suggested that the micronised drug materials had significantly different aerosolisation profiles when manufactured as single or combination formulations. In general, the greatest significant differences were observed between SS single drug and SS-BUD and SS-FFD combinations. Analysis of the in vitro performance for the SS only formulation suggested that the cohesive nature of SS (as predicted by the CAB and observed with AFM) led to tightly bound flocs that did not fully deaggregate upon aerosolisation.

Conclusions

It is suggested that the relationship between interparticulate interactions and in vitro performance of pMDIs suspension systems, when compared to direct measurement of the adhesion/cohesion forces, indicated good correlation. This approach may be useful in expediting the development of pMDI formulation and predicting performance.

Key words

adhesive/cohesive forces AFM in vitro testing pMDI suspensions 

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Daniela Traini
    • 1
    • 2
  • Paul M. Young
    • 1
  • Philippe Rogueda
    • 3
  • Robert Price
    • 2
  1. 1.Advanced Drug Delivery GroupFaculty of Pharmacy (A15), University of SydneySydneyAustralia
  2. 2.Pharmaceutical Surface Science Research GroupDepartment of Pharmacy, University of BathBathUK
  3. 3.AstraZeneca R&D CharnwoodLoughboroughUK

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