Meloxicam is an anti-inflammatory drug that could be interesting to deliver locally to the lungs to treat inflammation occurring in cystic fibrosis or chronic obstructive pulmonary disease (COPD). Spray drying conditions were optimized to prepare inhalable dry powders, from meloxicam aqueous solution with pH adjustment. A comparison study between non-porous and large porous particles (LPPs) was carried out to demonstrate the relevance of the aimed large size (>5 µm) and low density (<0.2 mg/cm 3) formulations. With the appropriate amount of porogen agent, ammonium bicarbonate, LPPs exhibited the same aerodynamic diameter and a higher deposited fraction than smaller but dense particles. The aerodynamic evaluation of LPPs showed that the fine particle fraction (FPF) reached up to 65.8%, while the emitted fraction (EF) reached 85.4%, both higher than for the non-porous particles. Stability tests demonstrated that, after 10 weeks of storage, no significant difference could be detected in the aerodynamic behaviour of the formulations. To the best of our knowledge this is the first time large porous particles, with enhanced aerodynamic properties, from an aqueous solution of meloxicam are reported.

Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.

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A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles. Mannitol and leucine were added when producing dry particles using nano-spray drying. The following investigations were implemented: dynamic light scattering, laser diffraction, surface tension measurement, scanning electron microscopy, X-ray powder diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, in vitro dissolution test, and in vitro aerodynamic assessment (Andersen Cascade Impactor). The particle diameter of the IBU was in the nano range. The spray-dried particles showed a spherical morphology. The drug release was rapid in artificial lung media. The products represented large fine particle fractions and proper aerodynamic diameters. We successfully created an inhalable powder, containing nano-sized IBU. Along with the exceptional aerodynamic performance, the ideal particle size, shape, and drug-release profile might offer a ground-breaking local therapy for CF.

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