Investigation into the influence of polymeric stabilizing excipients on inter-particulate forces in pressurised metered dose inhalers

D Traini, P M Young, P Rogueda, R Price

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Colloid probe atomic force microscopy (AFM) was utilised to quantify the cohesive forces of salbutamol sulphate in a model non-pressurised fluorinated liquid (mHFA), in the presence of increasing concentrations of poly(ethylene glycol) (PEG; molecular weight (MW) 200, 400 and 600). In addition, samples of PEG 400 (0.05-0.5%, v/w), were analysed in the presence of 0.001% (w/w) of poly(vinyl pyrrolidone) (PVP). In the absence of any stabilizing agents, strong attractive forces were present between particles. Increasing the concentration of the different MW PEG solutions in the mHFA system (up to 0.5%, v/w), significantly decreased the force of interaction (ANOVA, p < 0.05). The decrease in cohesion was particularly evident at very low concentrations of PEG (0.05-0.1%, v/w). Further data analysis (p < 0.05) suggested that the reduction in the force of cohesion was dependent on the concentration and molecular weight of PEG. The addition of low concentration of PVP to the PEG 400-mHFA system had the most significant influence on drug particle cohesion. In the presence of PVP, increasing addition of PEG 400 (0.05-0.5%, v/w) to the mHFA, resulted in no significant reduction in the force of cohesion (p > 0.05). Clearly, an understanding of the conformation of polymer molecules at interfaces is of vital importance when controlling the stability/flocculation behaviour of sterically stabilized pMDI suspensions. In this context, the use of the colloid probe AFM technique has provided a quantitative insight into the interactions of these complex systems and may be an invaluable asset during the early phase of formulation product development. (c) 2006 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalInternational Journal of Pharmaceutics
Volume320
Issue number1-2
DOIs
Publication statusPublished - 2006

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