The effects of polyvinyl alcohol on the in vitro stability and delivery of spray-dried protein particles from surfactant-free HFA 134a-based pressurised metered dose inhalers

Y. H. Liao, Stuart A. Jones, T. Nazir, Gary P. Martin, Marc Brown

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The objective of the present study was to investigate the physical stability of spray-dried proteins within surfactant-free hydrofluoroalkane (HFA) pressurised metered dose inhalers (pMDIs) during prolonged storage. Two model proteins (lysozyme and catalase) were spray-dried and stabilised in the presence of excipients, and subsequently suspended within HFA 134a. The pMDIs were stored valve-up for 6 months at room temperature (ca. 25 degrees C). Activities of the proteins were determined using biological assays and the fine particle fraction of the pMDIs was measured using a twin-stage impinger. The biological activities of catalase and lysozyme were found to be preserved in the presence of sugars and/or 80% hydrolysed polyvinyl alcohol (PVA) during spray drying. In addition, suspending the stabilised proteins within HFA for up to 6 months had little effect on their activity. The aerosolisation performance of lysozyme or catalase formulations containing either sucrose or trehalose as stabilisers appeared to deteriorate as a function of storage time. However, those formulations containing PVA were found to generate the greatest fine particle fraction, which in some cases was up to 50%, and to possess excellent physical stability during storage. The results indicated that the presence of PVA in the spray-dried stabilised protein particles could enhance the physical stability of particles, when suspended in the surfactant-free HFA MDI formulations, without affecting the protein stability upon prolonged storage. (c) 2005 Elsevier B.V All rights reserved.

Original languageEnglish
Pages (from-to)29-39
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume304
Issue number1-2
DOIs
Publication statusPublished - 4 Nov 2005

Keywords

  • spray-drying
  • protein stability
  • metered dose inhaler
  • pulmonary delivery
  • catalase
  • polyvinyl alcohol
  • lysozyme
  • hydrofluoroalkane
  • THERAPEUTIC PROTEINS
  • PRESERVATION
  • FORMULATION
  • SUSPENSION
  • LYSOZYME
  • LUNG

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