Formulation and process development of (recombinant human) deoxyribonuclease I as a powder for inhalation.
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.
Zijlstra
Gerrit S
GS
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, The Netherlands. G.S.Zijlstra@rug.nl
Ponsioen
Bart J
BJ
Hummel
Sylvia A
SA
Sanders
Niek
N
Hinrichs
Wouter L J
WL
de Boer
Anne H
AH
Frijlink
Henderik W
HW
D000280:Administration, Inhalation; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D004356:Drug Storage; D055119:Elastic Modulus / Q000187:drug effects; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007444:Inulin / Q000737:chemistry; D011208:Powders; D013183:Sputum / Q000737:chemistry / Q000187:drug effects*; D013696:Temperature; D014783:Viscosity / Q000187:drug effects
D005079:Excipients; D011208:Powders; D007444:Inulin; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I