Light Induced Fluorescence (LIF) was evaluated as a potential Process Analytical Technology (PAT) tool for the assessment of blend uniformity in lactose-based dry powder inhaler (DPI) blends containing low active pharmaceutical ingredient (API) concentrations (<1% w/w). This technique has the potential to overcome the limitations of near infrared spectroscopy in terms of sensitivity for low drug concentrations.
Selectivity for the tested API was assured. The sample size measured by LIF was estimated to be approximately
2 mg, and density increases seem to decrease the LIF signal intensity.
A good calibration model was obtained for blends containing API contents from 0.08% to 0.16% w/w. Linear regression was used to generate a calibration model, due to the simplicity of the spectral features of API and lactose, allowing the quantitative characterization of blending processes.
The assessment of the blend uniformity depends on the understanding of blending mechanisms and kinetics. Convective blending takes place in the first minutes with rapid decrease of the sample RSD to acceptable levels. Diffusive mixing will occur during longer blending times. Density may also influence the signal intensity. The definition of the blending end time is dependent on the understanding of the multiple events taking place through time in the powder bed, and on the use of appropriate mathematical tools, coupled with aerosol performance testing.
LIF may be a suitable sensitive PAT method for blend uniformity monitoring of low-dose lactose-based DPI formulations, with simple analysis, allowing both qualitative and quantitative assessments of the blend uniformity.