Comparing protein stabilisation effects of inositol to mannitol and trehalose in inhalable particles prepared by nano spray-drying
Michael Y.T. Chow1 & Jenny K.W. Lam1
1UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom
Summary
Pulmonary delivery of proteins offers enormous clinical potential, and it is desirable to formulate proteins into dry powders for enhanced storage stability. In this study, the potential of inositol as a stabilising agent was compared with mannitol and trehalose. Bovine serum albumin (BSA), as the model protein, was spray dried alone or with mannitol, (myo-) inositol or trehalose at equal mass ratio, using a nano spray dryer equipped with a mesh nebuliser. All particles exhibited a size distribution suitable for inhalation, with BSA-only particles having a median diameter of 3.84 µm. This reduced to 3.21-3.36 µm after incorporating stabilising agents. Contrast to pure BSA particles that showed a smooth spherical morphology, the spherical particles containing inositol or trehalose exhibited wrinkled surfaces, a desirable feature to promote deagglomeration. Inositol also resulted in a less residual moisture content (3.3%) than trehalose (5.0%) or pure BSA (5.4%), yet higher than that with mannitol (2.4%). While gel electrophoresis did not reveal detectable protein degradation across all formulations, size exclusion chromatography showed a reduction in monomer content of 4.8% in the absence of stabilisers. With inositol or trehalose, the reduction in monomer content decreased to 1.3% and 1.2%, respectively, implying protein stabilisation. To conclude, protein particles with an inhalable particle size distribution have been successfully prepared by nano-spray drying. Inositol showed comparable protein stabilising capacities to trehalose with less residual solvent, suggesting it as a promising excipient in the formulation of protein powders for pulmonary delivery.