Solid Dispersions of Chitosan Glutamate for the Local Delivery of Miconazole: Characterization and In Vitro Activity

ABSTRACT

The incorporation of miconazole nitrate (MCN) in mucoadhesive microparticles made of a water-soluble chitosan salt, chitosan glutamate (CHG) was studied. These solid systems may be proposed for buccal or vaginal applications against mycotic infections, taking advantage of the muco-adhesive and permeation enhancing properties of this polymer. Two series of solid dispersions were obtained by either spray-drying and lyophilization, under different formulation variables. The in vitro release of MCN from both the series of microparticles was analyzed at pH simulating the mouth or vaginal environments. A high amount (60 to 85%) of the loaded MCN was released quickly within the first 30 min both at pH 5.0 and 6.6 from all the systems, while the release did not further increase in the following 4 h. These results suggest that the released drug was the fraction of drug desorbed from the CHG particle surface, while a residual amount of drug remained associated or entrapped within them.

An in vitro microbiological assay was carried out against different strains of Candida. MCN- CHG lyophilized solid dispersions gave enhanced inhibitory activity on yeast growth compared to the free drug, whereas the inclusion of MCN in spray-dried microparticles generally did not improve the activity of the drug. The different physical properties of the two kinds of dispersions seemed to be at the basis of the observed different in vitro antimycotic activity.

Keywords:

Chitosan glutamate, miconazole, antimycotic activity, microparticles, mucoadhesion, drug delivery system.