Formulation of IN SITU gelling suppository containing Centella Asiatica extract spray-dried with Chitosan

Abstract

The in situ gelling suppositories containing Centella asiatica extracts spray-dried with chitosan were formulated with poloxamer mixtures in this investigation. An experimental factorial design was built to investigate the effects of five parameters on percentage production yield and percentage moisture content of spray-dried products. These factors concerned both formulation parameters (%solid content, %additive concentration and polymer: extract ratio) and spray drying parameters (inlet temperature and feed rate). The operating condition was to maximize production yields while minimizing moisture contents. First screening experiments consisting of 25-1 fractional factorial design revealed the most significant factors to be inlet temperature and %solid content (P < 0.01). Then, the optimal operating condition was estimated by response surface methodology. Central rotational composite design showed a quadratic model for %yield and a linear model for %moisture content were adequate (P < 0.05). The optimum region by overlay plot was carried out using the last condition to evaluate the repeatability of the spray-drying technique. The observed means obtained for yield and %moisture content were in range of the prediction intervals at 95% confidence level. The result clearly showed that the model fitted the experimental data well. The optimal microsphere formulation showed high loading efficiency of asiaticoside and madecassoside (84.25±1.01% and 86.64±0.54%, respectively), small size (5.19±0.02 μm), positive charge (32.87±1.39 mV) and good mucoadhesive property. Differential scanning calorimetry and powder x-ray diffraction studies revealed that the centella extract was molecularly dispersed with chitosan or/and existed in an amorphous state as a solid dispersion. The release from the optimal microspheres was fast. To prepare a novel in situ gelling suppositories with poloxamer mixtures, the mixtures of poloxamer 407 (18%) and poloxamer 188 (4%) existed as a liquid at room temperature, but gelled at 30–36°C with suitable gel strength and setting time. The analysis of release mechanism showed that the releases of asiaticoside and madecassoside were proportional to the square root of time, indicating that asiaticoside and madecassoside might be released from the suppositories by Fickian diffusion.