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.

The aim of this study was to develop oral lyophilisates with improved meloxicam (MEL) dissolution, optimizing each step of the preparation by design of experiments. First, meloxicam nanosuspensions were prepared by high-pressure homogenization (HPH), using PVP, Poloxamer or PEG as stabilizers and were subjected to freeze-drying using mannitol as cryoprotectant. The effects of the stabilizers and cryoprotectant were assessed and an optimal formulation was generated within the Design Space where the particle sizes and the PDIs are at their lowest values. The optimal formulation was used at the preparation of oral lyophilisates. Sodium alginate (SA) and croscarmellose sodium (CCS) were tested as matrix forming agents and three different freezing regimes were applied. The formulation was optimized, choosing the polymer that yielded both high mechanical strength and fast MEL dissolution. Poloxamer led to particle size reduction down to 10.27% of the initial size, meaning 477.6±7.5nm, with a slight increase during freeze-drying process. PEG showed lower nanonizing capacity during HPH, but freeze-drying produced further diminution of the particle size. Since Poloxamer provided advanced size reduction while preserving MEL crystallinity, it was used for the optimized formulation containing 1% Poloxamer and 5% mannitol added before freeze-drying. SA showed good structural properties when compared to CCS and allowed fast MEL dissolution at low ratios. The optimal formulation contained 1.157% of SA was subjected to thermal treatment during freeze-drying. It disintegrated in 3.33s and released 77.14% of the MEL after 2min. The quality by design (QbD) approach for the development of pharmaceutical products ensured high quality of the dosage form and good understanding of the preparation process.

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