Effect of ethanol as a co-solvent on the aerosol performance and stability of spray-dried lysozyme

• Published in: International journal of pharmaceutics 2016-11, Vol.513 (1-2), p.175-182
• Main Authors: Ji, Shuying, Thulstrup, Peter Waaben, Mu, Huiling, Hansen, Steen Honoré, van de Weert, Marco, Rantanen, Jukka, Yang, Mingshi
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosol performance; Aerosols; Chemistry, Pharmaceutical - methods; Drug Compounding - methods; Drug Stability; Ethanol; Ethanol - chemistry; Lysozyme; Muramidase - administration & dosage; Muramidase - chemistry; Protein stability; Solvents - chemistry; Spray drying; Water - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.09.025

[Display omitted] 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.