Analysis of the variance components in a pharmaceutical aerosol product: lodoxamide tromethamine

The contributions of several components to the variance in lodoxamide delivery from lodoxamide tromethamine metered-dose aerosol containers have been estimated. Two aerosol lots, manufactured with mean diameters of 2.3 and 7.2 micron, exhibited approximately equal variances. The variance was apportioned to the following components: container-to-container, 27%; mouthpiece-to-mouthpiece 18%; valve-to-valve, 11%; assay, 6%. The largest single contribution to the variance (38%) is attributed to unassignable variations which include within-container variations in the dose; quality improvement efforts should concentrate on this area. Little effort should be expended to minimize the assay, valve delivery, or mouthpiece variation as their contribution to lodoxamide dose variation is small. Likewise, the bulk drug particle size did not contribute appreciably to within-lot dose variation.