Effect of ethanol as a co-solvent on the aerosol performance and stability of spray-dried lysozyme.
In the spray drying process, organic solvents can be added to facilitate drying, accommodate certain functional excipients, and modify the final particle characteristics. In this study, lysozyme was used as a model pharmaceutical protein to study the effect of ethanol as a co-solvent on the stability and aerosol performance of spray-dried protein. Lysozyme was dissolved in solutions with various ratios of ethanol and water, and subsequently spray-dried. A change from spherical particles into wrinkled and folded particles was observed upon increasing the ratio of ethanol in the feed. The aerosol performance of the spray-dried lysozyme from ethanol-water solution was improved compared to that from pure water. The conformation of lysozyme in the ethanol-water solution and spray dried powder was altered, but the native structure of lysozyme was restored upon reconstitution in water after the spray drying process. The enzymatic activities of the spray-dried lysozyme showed no significant impact of ethanol; however, the lysozyme enzymatic activity was ca. 25% lower compared to the starting material. In conclusion, the addition of ethanol as a co-solvent in the spray drying feed for lysozyme did not compromise the conformation of the protein after drying, while it improved the inhaled aerosol performance.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Shuying
S
Ji
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark.
Peter Waaben
PW
Thulstrup
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Huiling
H
Mu
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Steen Honoré
SH
Hansen
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Marco
M
van de Weert
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Jukka
J
Rantanen
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road No. 103, 110016, Shenyang, China. Electronic address: mingshi.yang@sund.ku.dk.
Mingshi
M
Yang
D000280:Administration, Inhalation; D000336:Aerosols; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry*; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000336:Aerosols; D012997:Solvents; D014867:Water; D000431:Ethanol; D009113:Muramidase
Aerosol performance; Ethanol; Lysozyme; Protein stability; Spray drying