Production of cromolyn sodium microparticles for aerosol delivery by supercritical assisted atomization

Abstract

The purpose of this study was to produce cromolyn sodium (CS) micrometric particles with controlled particle size (PS) and PS distribution (PSD) suitable for aerosol delivery, using a supercritical fluids-based process. CS was micronized using the supercritical assisted atomization (SAA) technique at different solute concentrations in water and different precipitation temperatures. Two techniques were used to measure PS and PSD of produced particles: scanning electron microscopy image analysis and laser scattering analysis. The 2 techniques were compared to provide a complete description of the powder obtained. High-performance liquid chromatography analysis was used to verify the absence of degradation of CS after micronization; differential scanning calorimetry, thermogravimetric analysis (TGA), and X-ray analysis were performed to study the effect of operative conditions on the crystalline structure and on the water content of SAA micronized particles. The CS particles obtained were spherical, with a volumetric percentage of particles with a diameter ranging between 1 and 5 μm of 50% to 66%. The precipitation temperature had no significant effect on PSD, but high drying temperatures led to product degradation. Increasing the concentration of CS in water solution produced an increase in PS of the micronized particles. TGA showed that the micronized CS had a different hydration state than the untreated CS did. The micronized product was stable after 12 months of storage, and no modifications in structure, morphology, or crystallinity were detected. In conclusion, SAA is an efficient technique for micronization of CS, and stable spherical amorphous particles suitable for aerosol delivery can be produced.

Precipitation parameters and the cytotoxicity of chitosan hydrochloride microparticles production by supercritical assisted atomization

“…Therefore, the discrepancy in overestimated DLS data resulted from the expected agglomerates formation, but the trend of the effects of SAA parameters on the mean CH particle sizes was consistent with that of the effects of parameters in the FESEM analyses. Similar results were reported previously [26,32,33]. …”

“…4 and 5, the second effect was observed in the present study; thus, smaller particles were obtained with a lower solution concentration. Similar results have been reported for relevant SAA processes [15,[18][19][20]24,25,32,33]. The effect of saturator temperature (T S ) in the range of 313.2 to 363.2 K (Table 1, runs #C1, #C5-#C7) on the CH particle size is shown in Fig.…”

Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer

“…Additional functional groups covalently attached to ketone, such as the ether moiety and carboxylate display meaningful peaks in the Raman spectra. The asymmetric stretching vibrational modes of carboxylic acid moiety occur near 1574 cm –1 , and this is found in the Raman spectra of CS and all of the metal complexes that were analyzed . The CH 2 next to the carbonyl presents a strong band as a result of CH 2 deformation at 1415 cm –1 ; such a peak is observed on the Raman spectra obtained for CS.…”

“…The asymmetric stretching vibrational modes of carboxylic acid moiety occur near 1574 cm −1 , and this is found in the Raman spectra of CS and all of the metal complexes that were analyzed. 30 The CH 2 next to the carbonyl presents a strong band as a result of CH 2 deformation at 1415 cm −1 ; such a peak is observed on the Raman spectra obtained for CS. Changes observed in the Raman spectra of the metal complexes included a shift in this peak occurring at around 1430 cm −1 in Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca.…”

Supercritical fluids applications in nanomedicine

“…It has been successfully used to produce fine particles of several pharmaceuticals and composite microparticles for drug release [60][61][62][63][64]. In this process, the organic solution and SC-CO 2 form an expanded liquid in a saturator.…”