Raman spectroscopy was used to evaluate the effects of temperature and humidity on the physicochemical stability of inhalable spray-dried (SD) powders containing budesonide (BUD) and crystalline or amorphous lactose. Powders prepared by spray drying of BUD-lactose solution or suspension containing lactose crystals in BUD solution were stored for 0, 1 and 7 days at 25 °C/60 RH or 40 °C/75 RH. Bulk powders along with the large and small particle size fractions collected on stages 2 and 5, respectively, of the Next Generation Impactor (NGI) were chemically characterised. SD powder from solution contained BUD and lactose in amorphous form and both components were homogeneously distributed in bulk and in the particles collected from the two NGI stages. In contrast, SD powder from suspension showed heterogeneous distribution of lactose and drug in the particles containing crystalline lactose. After 1 day of storage at either condition, recrystallisation and changes in the chemical composition of the particles for the SD powder from solution occurred. The number of drug-only particles increased by 70 on stage 5, whereas most particles on stage 2 still contained both drug and lactose. These changes were not observed in the SD powder from suspension after storage, confirming superior stability of the SD powder obtained from suspension.
Keywords: Budesonide; Crystallinity; Dry powder aerosols; Lactose; Raman spectroscopy; Spray dry; Storage stability.
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