Pulmonary drug administration provides a platform for the effective local treatment of various respiratory diseases. Application of nano-sized active ingredients results in higher bioavailability because of their large specific surface area. Extra-fine dry powder inhalers reach the smaller airways, further improving therapeutic efficiency. Poorly water-soluble meloxicam was the selected active ingredient. We aimed to decrease the particle size into the nano range by wet milling and producing extra-fine inhalable particles via nano spray-drying. The diameter of the drug was reduced to 138 nm. The particle size of the dry products was between 1.1 and 1.5 µm, and the dispersed diameter was between 500 and 800 nm. Owing to the excipients (poly-vinyl-alcohol, leucine), the spray-dried particles presented nearly spherical morphology. The drug became partially amorphous. Thanks to the improved surface area, the solubility and the released and the diffused amount of the meloxicam increased in artificial lung media. The in vitro aerodynamic measurements showed that the leucine-containing formulations had outstanding fine particle fraction (FPF) deposition with 1.3 µm mass median aerodynamic diameter (MMAD). The aerodynamic particle counter test also proved the extra-fine aerodynamic particle size. The in vitro cell line experiments revealed the non-cytotoxicity of the products and the suppression of the interleukin concentration. Overall, the powders are suitable for deep pulmonary delivery and the local treatment of lung inflammations.
Keywords: A549 cell line; Aerodynamic particle counter; Andersen cascade impactor; Dry powder inhaler; Meloxicam; Nano spray-drying.
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