Development of excipients free inhalable co-spray-dried tobramycin and diclofenac formulations for cystic fibrosis using two and three fluid nozzles.

This study aims to investigate the effect of physicochemical properties and aerosol performance of two (2FN) and three-fluid nozzles (3FN) on the inhalable co-formulation of tobramycin and diclofenac dry powders. Combination formulations of tobramycin and diclofenac at 2:1 and 4:1 w/w ratios were prepared at a laboratory scale using a spray dryer in conjunction with a 2FN or 3FN. Powder size, morphology, solid-state characteristics, and aerodynamic and dissolution properties were characterised. The nozzle types and the formulation composition influenced the yield, particle size, solid-state properties, aerosolization behaviour and dissolution of the co-spray dried formulations. In particular, using the 2FN the co-spray dried formulation of tobramycin and diclofenac at 2:1 w/w showed smaller particle size (D50, 3.01 ± 0.06 µm), high fine particle fractions (FPF) (61.1 ± 3.6% for tobramycin and 65.92 ± 3 for diclofenac) and faster dissolution with approx. 70% diclofenac released within 3 h and approx. 90% tobramycin was released within 45 min. However, the 3FN for the co-spray dried formulation of tobramycin and diclofenac at a 2:1 w/w ratio showed a larger particle size (D50, 3.42 ± 0.02 µm), lower FPF (40.6 ± 3.4% for tobramycin and 36.9 ± 0.84 for diclofenac) and comparative slower dissolution with approx. 60% diclofenac was released within 3 h and 80% tobramycin was released within 45 min. A similar trend was observed when the tobramycin to diclofenac ratio was increased to 4:1 w/w. Overall results suggest that spray drying with 2FN showed a superior and viable approach to producing excipients-free inhalable co-spray dried formulations of tobramycin and diclofenac. However, the formulation produced using the 3FN showed higher enrichment of hydrophobic diclofenac and an ability to control the tobramycin drug release in vitro.

The application of in vitro cellular assays for analysis of electronic cigarettes impact on the airway.

Electronic (e)-cigarettes have been marketed for more than a decade as an alternative to conventional cigarettes. Their popularity and use among adolescents have grown significantly during recent years. While e-cigarettes do not release carcinogenic aromatic hydrocarbons, they can generate reactive carbonyls and radicals during the heating process in vitro. Emphasis has been placed in recent studies to introduce more rigorous and physiologically relevant in vitro models to characterise the toxicological profile of e-cigarettes. However, significant challenges are present due to difficulties for the developed systems to fully represent the in vivo inhalation settings. Furthermore, research protocols that fail to simulate the characteristics of e-cigarettes can affect the findings of in vitro studies. This review will illustrate the status quo of e-cigarette assays in vitro, discussing the various cellular assays used for evaluating the safety profile of e-cigarettes. Future directions will also be provided to better assist the scientific community in interpreting the health risks of e-cigarettes.