Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles.

PURPOSE

Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance.

METHODS

Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated.

RESULTS

The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F and F were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min.

CONCLUSION

SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime.