Optimization and Formulation of Cinnarizine-Loaded Chitosan Microspheres in Liquid Dosage Form for Pediatric Therapy

Cinnarizine pediatric preparation is extemporaneously prepared from adult tablets or capsules that are unstable in liquid dosage form. The aim of this work is to develop cinnarizine oral pediatric formulation with improved stability and organoleptic properties as well as to achieve ease of administration. For this purpose, cinnarizine-loaded microspheres of chitosan cross-linked with tripolyphosphate anion were prepared. A full 23 factorial design of experiment approach was employed to evaluate the individual and the combined effect of the independent variables namely, concentration of each of chitosan (XA), tripolyphosphate (XB), and that of cinnarizine (XC) on the different responses namely drug entrapment efficiency, drug content, percentage yield and drug release rate for the prepared microspheres. Statistical analysis through response-surface methodology as well as contour plots was assessed. The optimized microspheres (formula 4) showed 93.6±3.3 % percentage yield, 74.3±0.8 mg drug loading, 74.3±0.8 % encapsulation efficiency and 0.19 µm particle size. Hence, it was subjected to stability study of cinnarizine in the dry microspheres immediately thereafter preparation through transmission electron microscope, x-ray diffractometry, Fourier transform infrared spectroscopy and differential scanning calorimetry. The microspheres were further dispensed in the prepared syrup and the suspension was subjected to accelerated stability study, as mentioned in the International Conference on Harmonization (ICH) guidelines. Subsequently, oral bioavailability study of (formula 4) microspheres was conducted on rats and compared with aqueous suspension of the plain drug. Formula 4 complied successfully with ICH guidelines and experienced enhanced extent of bioavailability with long mean residence time (MRT).