The acid lability of rosuvastatin hinders the preparation of mixed combination formulations\nof rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to\ndevelop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin\nand clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective\nat inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore,\nthe multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate\nbetween the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed\ndissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel\ncore tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin,\nachieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting\nmultilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix®\nand Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum\nplasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the\narea under the plasma-concentration time curve (AUC) between the test and reference formulations.\nThe storage stability tests showed that the amounts of acid degradation products and total impurities\nwere comparable to that of the reference drug. In conclusion, the present study successfully developed\na stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the\npatient compliance in combination therapy for cardiovascular diseases.
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