Preparation of Chlorpheniramine Maleate-loaded Alginate/Chitosan Particulate Systems by the Ionic Gelation Method for Taste Masking

Abstract

Chlorpheniramine maleate (CM) is widely used as an antihistaminic drug but it is very bitter and as yet no mouth dissolving/disintegrating taste-masked preparation that might be useful for pediatric and geriatric patients is available in the market. The purpose of this research was to mask the bitter taste of CM by formulating microspheres of the taste-masked drug. This work was done to develop alginate/chitosan particles prepared by ionic gelation (Ca(2+) and Al(3+)) for the CM release. The effect of different chitosan and Ca(2+) concentrations on taste masking and the characteristics of the microspheres were investigated. Ca(2+) and Al(3+) alginates microspheres of CM were prepared using cross-linked insoluble complexes that precipitate, incorporating the drug. Formulations were characterized for particle size and shape, entrapment efficiency, fourier transform spectroscopy (FTIR), x-ray diffraction (XRD), and differential scanning calorimetry (DSC), bitter taste threshold and in vitro drug release in simulated gastrointestinal fluids. FTIR, XRD and DSC demonstrated unstable characters of CM in the drug-loaded microspheres and revealed an amorphous form. Also, the peak of alginate microparticles (Ca(2+) and Al(3+) ions) in all formulations remained the same, with low intensity of spectrum. The results of DSC, X-ray diffraction and FTIR showed the presence of several CM chemical interactions with alginate and ions (Ca(2+) and Al(3+)). The microsphere formulations showed desirable drug entrapment efficiencies (62.2-94.2%). Calcium/aluminum alginate retarded the release of CM at low pH = 1.2 and released the drug from microspheres slowly at pH = 6.8, simulating intestine pH. The drug release duration and the release kinetics were dependent on the nature of the polymers, the cation concentrations, and valences (Ca(2+) and Al(3+)). The drug release rate was decreased by an increase in chitosan and cation concentrations. The results of the present study indicated that oral preparation of CM with an acceptable taste is feasible.