Formulation and process development of (recombinant human) deoxyribonuclease I as a powder for inhalation

Gerrit S Zijlstra, Bart J Ponsioen, Sylvia A Hummel, Niek Sanders, Wouter L J Hinrichs, Anne H de Boer, Henderik W Frijlink

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)

Abstract

A formulation and process development study was performed to formulate recombinant human deoxyribonuclease I as a powder for inhalation. First, excipient compatibility (with bovine DNase as a model substance) was examined with a stability study at stressed conditions (60 and 85 degrees C) while monitoring for occurrence of the Maillard reaction. Next, powders for inhalation were prepared by spray drying and spray freeze drying. We found that spray drying with inulin as stabilizer resulted in the best powder for inhalation. Finally, an ex-vivo test with the spray dried rhDNase I/inulin powder significantly decreased elastic and viscous moduli of sputum from five cystic fibrosis patients.

Original languageEnglish
Pages (from-to)358-368
Number of pages11
JournalPharmaceutical development and technology
Volume14
Issue number4
DOIs
Publication statusPublished - 2009

Keywords

  • DNase
  • Dry powder inhalation
  • Maillard reaction
  • Protein
  • RhDNase
  • Sputum
  • Stabilization
  • deoxyribonuclease
  • dornase alfa
  • inulin
  • article
  • drug formulation
  • excipient compatibility
  • female
  • freeze drying
  • glycation
  • human
  • lung fibrosis
  • nonhuman
  • priority journal
  • process development
  • spray drying
  • sputum

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