Evaluating drug distribution in rat lung by mass spectrometry imaging after dry powder insufflation: Comparison of jet-milling, spray-drying, and thin film freezing

Abstract

Uniform drug distribution within lungs is crucial for effective treatment of lung diseases when delivered via the pulmonary route. Imaging techniques such as gamma scintigraphy, positron emission tomography, and single-photon emission computed tomography, and others, have limitations, including the need for tagging, product reformulation, and in vitro validation. Mass Spectrometry Imaging (MSI) overcomes these drawbacks by visualizing drug distribution within lungs without tagging. In this study, voriconazole dry powder formulations for inhalation were prepared by three different methods: jet-milling, spray-drying, and thin film freezing (TFF). MSI was used to differentiate voriconazole distribution in rat lung after dry powder insufflation. The TFF-processed voriconazole powder, consisting of brittle, easily shearable nanoaggregates, exhibited the most homogeneous distribution in lung tissue, with the lowest airway-to-lung voriconazole deposition ratio (1.27), followed by spray-dried (1.76) and jet-milled (2.73). This enhanced distribution is attributed to the smaller particle size after disaggregation and rapid movements on the liquid surface. The results suggest that TFF dry powders for inhalation can enhance treatment efficiency and reduce toxicity for lung diseases, further supporting TFF as a promising method to formulate powder for pulmonary drug delivery.