Stabilisation of deoxyribonuclease in hydrofluoroalkanes using miscible vinyl polymers

Stuart A. Jones, Gary P. Martin, Marc Brown

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
34 Downloads (Pure)

Abstract

A mix of biocompatible macromolecules (poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP)) has been shown previously to enhance the physical stability of non-aqueous pharmaceutical suspensions. The aim of this work was to assess the feasibility of employing such a combination to facilitate the formulation of deoxyribonuclease I (DNase I) in a metered dose inhaler (MDI) using hydrofluoroalkane (HFA) propellants. DNase I was combined with the selected excipients and formed into an inhalable microparticle by spray-drying. When spray-dried alone DNase I lost almost 40% of its original biological activity, but stabilising DNase I with trehalose and PVA (DTPVA) retained 85% biological activity and trehalose, PVA and PVP (DTPVAPVP) retained 100%. Suspending the DTPVAPVP microparticles within a HFA pMDI for 24 weeks led to no further reduction in the biological activity of DNase I and the formulation delivered almost 60% of the dose expelled to the second stage of a twin-stage impinger. The solubility of PVP in HFA propellants suggests that the enhanced physical stability observed with PVA and PVP may partially be as a result of steric stabilisation. However, the large zeta potential associated with the suspensions suggested that charge stabilisation may also influence the pMDI physical stability. (c) 2006 Elsevier B.V All rights reserved.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalJournal of Controlled Release
Volume115
Issue number1
DOIs
Publication statusPublished - 28 Sept 2006

Keywords

  • METERED-DOSE INHALERS
  • HUMAN DNASE-I
  • CYSTIC-FIBROSIS
  • SHORT-TERM
  • DISPERSIONS
  • STABILITY

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