International journal of pharmaceutics
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High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve this, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would produce inhalable particles with surfaces enriched in rifampicin. ⋯ In vitro aerosolization (fine particle fraction) determined by next generation impactor (NGI), dramatically improved from 29.5 ± 0.2% (kanamycin-only) to 78.2 ± 1.3% (kanamycin-rifampicin combination). The combination powder was flake-shaped in morphology, stable at 15% and 53% RH and 25 ± 2 °C during one-month storage in an open Petri dish, and non-toxic (up to 50 µg/mL) to human alveolar and bronchial cell-lines. Surface enrichment of kanamycin by hydrophobic rifampicin improves aerosolization, which may help to combat drug-resistant local infections by facilitating high dose delivery to deep lung.
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Amorphous powders are thermodynamically unstable, significantly impacting the processing, storage and performance of a product. Therefore, stabilization of the amorphous contents is in demand. In this study, disodium cromoglycate (DSCG) powder was chosen as a model drug because it is amorphous and highly hygroscopic after spray drying. ⋯ However, after one month storage at 75% RH, SD formulation containing 10% NaSt showed a reduction in FPF, while formulations containing 50% or 90% NaSt showed no change. The underlying mechanism was that NaSt increased the crystallinity of the powders and its presence on the particle surface reduced particle aggregations and cohesiveness. However, NaSt at high concentration could reduce dissolution rate, which needs to be taken into consideration.