Formulation and comparison of spray dried non-porous and large porous particles containing meloxicam for pulmonary drug delivery

Abstract

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.

Formulation and aerodynamic evaluation of carrier-free dry powder inhalation systems containing meloxicam

“…HA, as well as PVA, was used in order to stabilize the structure of formulations (Martinelli et al, 2017). However, literature data report that sodium hyaluronate could promote surface roughness of spray dried particles (Li et al, 2017), we did not detected the same intensive effect (Chvatal et al, 2019). However the surface roughness of porous formulations was much lower, slight wrinkles could be detected on the surface of the large sized spherical particles.…”

“…Formulations prepared with 1.5 and 2.0 mg/mL AB concentrations had the same geometric diameter (Chvatal et al, 2019). Porous formulations also have narrow size distribution with Span ≤2.0.…”

“…and 1595 cm -1 (Fig. 12) (Chvatal et al, 2019). (Chvatal et al, 2017) and MX (at 13.22°, 15.06°, 26.46° 2-theta) (Aytekin et al, 2018;Chvatal et al, 2019).…”

“…12) (Chvatal et al, 2019). (Chvatal et al, 2017) and MX (at 13.22°, 15.06°, 26.46° 2-theta) (Aytekin et al, 2018;Chvatal et al, 2019). The fact that the characteristic peaks of crystalline APIs are missing from the diffractogram of spray dried samples (MXP-SD, MX-SD) indicates that the raw material becomes amorphous during the spray drying (Fig.…”

“…Non-porous formulations with PVA+LEU combination decreased the density from 0.37 till 0.34 g/cm 3 (MXP/LEU 20 /PVA 0.25 is the lowest), but the difference was not significant. Despite the fact that polymers increase the viscosity of solutions, PVA and HA had no significant effect on the density of the spray dried particles (Chvatal et al, 2017;Chvatal et al, 2019). There were detected significant differences in the tap densities of the two formulation types.…”