Nano-Spray-Dried Levocetirizine Dihydrochloride with Mucoadhesive Carriers and Cyclodextrins for Nasal Administration

Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 mu m, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 mu m. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 degrees C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with beta-cyclodextrin showed the highest permeability (188.37 mu g/cm(2)/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC.

Automated summary

This study developed composite powders containing levocetirizine dihydrochloride (LC) for nasal administration using three mucoadhesive polymers and four cyclodextrin species. The LC was in the form of a zwitterion after neutralization and the product exhibited an amorphous state. The average particle size of the microparticles ranged from 2.42 to 3.44 μm, except for those containing a polyvinyl alcohol excipient, which had a larger diameter of 29.80 μm. The spray-dried powder with beta-cyclodextrin showed the highest permeability, while other cyclodextrins and polymer excipients showed similar or slightly higher penetration abilities than LC.