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Therapeutic antibodies offer a potential treatment for, or means of protection against, airborne infections. For this application, it may be desirable to deliver the antibody directly into the nasal cavity, one of its potential sites of action, since this would be more efficient and convenient than systemic administration. Formulations of a model antibody (human IgG) were developed using albumin, sodium chloride and disaccharides. A combination of these excipients allowed the efficient spray-drying (yield>70%) of the antibody into a microparticulate (1-15 microm) dry powder that was rapidly soluble in aqueous media. The water content and crystallinity of the formulations were also measured, with both properties being affected by the substitution of some of the sodium chloride in the formulation, with lactose. The antibody was found to be stable following the formulation process, as determined by gel-electrophoresis, field-flow-fractionation and enzyme-linked immunosorbent assay. Incubation of an in vitro epithelial cell line in the presence of solutions of the formulations (at concentrations of up to 2500 microg/mL) was found not affect cell viability. The aerosolisation properties of the formulations were tested using Bespak's "Unidose-DP", dry-powder nasal device. The powder aerosol was analysed by laser diffraction, high-speed video and dose deposition in Bespak's nasal cast model. For the latter experiment, a range of additional excipients were either dissolved in the spray-drying liquid feed (leucine), or blended with the spray-dried powder formulation (magnesium stearate, Aerosil and lactose). The major dose deposition site of the standard spray-dried formulation was the nasal vestibule (approximately 55%). The addition of leucine and Aerosil resulted in a 10% increase in the deposition beyond the nasal vestibule, with approximately 45% of the delivered dose being deposited in the turbinates, olfactory region, and nasal-pharynx.

The behaviour of the lecithin Epikuron 200 was studied in solution in a chlorofluorocarbon (CFC) aerosol propellant (P113) using light scattering to determine the micellar structure as a function of temperature. At room temperature Epikuron 200 formed micelles with a radius of approximately 25 nm. The radius increased with decreasing temperature until a phase boundary was reached at 15–16°C, below which the micellar radius increased rapidly to 150–250 nm. This was accompanied by a large increase in the viscosity and turbidity of the solution. We consider that this behaviour is due to the formation of large wormlike micelles similar to those reported for lecithin in cyclohexane. The adsorption of Epikuron 200 on salbutamol sulphate was measured over this temperature range. The adsorbed amount of Epikuron 200 increased with decreasing temperature, and the hemimicelle concentration decreased rapidly at a temperature corresponding to the threshold for the formation of wormlike micelles. It is likely that these structures do form in CFC-MDI systems (particularly during cold-fill formulation), and that the structure of the adsorbed surfactant layer changes at low temperature. This may have implications for the formulation of stable aerosol suspensions.