Protein conformational stability in the hydrofluoroalkane propellants tetrafluoroethane and heptafluoropropane analysed by Fourier transform Raman spectroscopy

• Published in: International journal of pharmaceutics Vol. 186; no. 1; pp. 31 - 41
• Main Authors: Quinn, Éilı́s Á, Forbes, Robert T, Williams, Adrian C, Oliver, Martin J, McKenzie, Lesley, Purewal, Tol S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-09-1999
• Subjects: Drug Stability; Fourier transform Raman spectroscopy; Heptafluoropropane; Hydrocarbons, Fluorinated - administration & dosage; Hydrofluoroalkane propellant; Nebulizers and Vaporizers; Protein; Protein Conformation; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Stability; Tetrafluoroethane; Stability; Tetrafluoroethane; Fourier transform Raman spectroscopy; Hydrofluoroalkane propellant; Heptafluoropropane; Protein
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00135-0

Due to the inherent structural instability of proteins, development of chlorofluorocarbon (CFC) free metered dose inhalers (MDIs) containing these biomolecules is beset with numerous challenges. In assessing the conformation of proteins in any medium, both secondary and tertiary structures need to be elucidated. This study uses Fourier transform (FT-) Raman spectroscopy to probe protein conformational stability in hydrofluoroalkane (HFA) propellants. Assignments of molecular modes for lysozyme as a solid and in aqueous solution, and for the first time, HFAs tetrafluoroethane (HFA 134a) and heptafluoropropane (HFA 227) are given. The Raman spectra provided molecular structural information on the peptide backbone, disulfide bonds and C-C stretching vibrations of hen egg lysozyme, enabling the secondary conformation of protein in HFA propellants to be determined; structural integrity of this robust model protein was maintained in both propellants. These results demonstrate that FT-Raman may be a useful tool for the optimisation of protein MDI formulations.