Enhancing dissolution properties of cinnarizine by enteric polymers

Abstract

Introduction: Poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic environment of stomach, tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability.Aim: In this work the influence of plasticizers (polyethylene glycol, glycerin, methylparaben and propylparaben) on inhibitory effect of Eudragit S100 on Cinnarizine crystallization in buffer solution (pH=6.8) was assessed.Method: Upon induction of supersaturation in buffer solution using a pH shift method, precipitation was assessed as a function of time. Samples including the solid dispersions or physical mixtures containing polymer and plasticizer were prepared and Cinnarizine was added to each sample physically and characterized using dissolution studies. Dissolution analyses were conducted at supersaturated conditions using a pH change method and the area under the concentration curve values were calculated for each evaluated composition to provide a quantitative means of comparing the extent of supersaturation.Results: Superior supersaturation stabilizing effect was observed using solid dispersion formulations containing polyethylene glycol, methylparaben or propylparaben as plasticizers in comparison with Eudragit alone, while this superiority was’t detected with physical mixture of mentioned plasticizers; In addition, solid dispersion and physical mixture formulations containing glycerin and Eudragit, not only had no advantage in stabilizing supersaturation over Eudragit, but also presented a lower precipitation inhibition effect compared with Eudragit. Interaction between drug and polymer which was confirmed by FT-IR and DSC was necessary for supersaturation stabilization.Conclusion: From these finding, we are convinced that adding polyethylene glycol, methylparaben and propylparaben in Eudragit as a solid dispersion formulation and mixing this formulatin with Cinnarizine might be beneficial to improve the dissolution and bioavailability of Cinnarizine while addition of glycerin in Eudragit as a solid dispersion or physical mixture formulation might reduce the inhibitiory effect of Eudragit on precipitation of Cinnarizine.