Preparation of human serum albumin microaggregates labelled with §9§9[superscript]m to examine the nasal deposition and clearance of suspended pharmaceutical formulations

grantor: University of TorontoIn order to simulate the intranasal drug distribution of budesonide suspension aerosol, a tracer particle having a size distribution similar to this parent pharmaceutical was developed. This particle can be easily labelled with the $\gamma$-emitting radionuclide technetium-99m, and permits the study of deposition and subsequent movement of the formulation. Microaggregated human serum albumin (HSA) particles of about 2-3 microns in size were prepared by denaturing human serum albumin with a stabilizer and surfactant in a boiling water bath. By carefully controlling the time of thermal denaturation, microaggregates with the desired particle size distribution were prepared. Microaggregates were labelled with Tc-99m by adding diluted stannous chloride to reduce the $\rm\sp{99m}$Tc(VII) to $\rm\sp{99m}$Tc(V) and subsequently bind the $\rm\sp{99m}$Tc to the albumin. Polycarbonate membrane filters (Nuclepore) were utilized to perform particle size analysis by differential filtration. In addition, a quantitative, non-invasive three-dimensional image of human serum albumin microaggregates was obtained by using the laser confocal scanning microscope (Bio-Rad 600). The aerodynamic size distribution of microaggregates suspended in distilled water were verified by a single-particle, laser sizing system based on the time-of-flight data. Fifty percent of dried, aerosolized microaggregate particles were determined to be smaller than 2.040 microns in aerodynamic size, compared to 2.099 microns of the parent pharmaceutical. The characteristics of the tracer particles in an aqueous vehicle after nebulization was studied with an Andersen Impactor. Using a versatile shear cell, the diffusion coefficients of $\rm\sp{99m}$Tc microaggregates and of the parent pharmaceuticals in a viscous vehicle were compared.M.Sc