Development of an aqueous nasal spray formulation containing granulocyte colony stimulating factor

Tanya Shukla, David Ward, Mark Hammond, Ben Forbes

The aim of the project was to assess the feasibility of developing an aqueous nasal spray formulation for granulocyte colony stimulating factor (GCSF) by addressing concerns that formulation excipients and shear stress on actuation may cause structural break down of protein.   Four different formulations containing bovine serum albumin (BSA) as a model protein, plus a fifth GCSF-containing formulation with the same composition as one of the BSA formulations, were evaluated for structural stability over a period of 4 weeks and tolerance to actuation-generated shear stress.  Circular dichroism, capillary isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) on reduced and non-reduced gels were performed to evaluate the protein structure in unactuated and actuated samples of each of the formulations.  Protein assays and BSA-specific enzyme-linked immunosorbent assays (ELISA) were performed to determine any loss of protein concentration.  United States Food and Drug Administration (FDA) guidelines were followed to evaluate the in vitro performance of the formulations when actuated as nasal sprays using pump devices.  The chemical and structural stability of the proteins were retained in the formulations that were tested.  All formulations complied with the FDA requirements, showing negligible respirable fraction (% of droplets of a size inhalable into lungs), plume angles ranging from 34°-42° (indicative of good nasal deposition) and an elliptical spray pattern.  Overall, the feasibility of developing GCSF formulations as nasal sprays was established, although long-term stability tests need to be carried out to develop a product commercially

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