Escitalopram Oxalate Tablets Manufacturing Process Improvement And Quality Control

Eseitalopram oxalate tablet is a new generation of antidepressant used for depressive disorder in clinical therapeutics. This work was aimed to produce Eseitalopram oxalate tablet with higher quality and stability and establish the specification of the product as well. The main achievements of the work are as follows:1. A process consisting of wet granulation, drying, mixing, tabletting and coating was developed for the prepartion of Eseitalopram oxalate tablet. Since granulation process was improved and OPADRY(?) Ⅱ (85G white) instead of TiO2-PEG6000-PHMC, was employed as coating material, the stablity of the product was enhanced significantly.2. HPLC methods for the demnation of Escitalopram oxalate and L-isomer were set up and validated as well. A specification of Escitalopram oxalate tablet was proposed, including appearance, dissolution, assay, L-isomer, related substances, uniformity.3. Impurities were investigated and the unknown impurity, denoted as Impurity C, was idetified and determined by LC-MS. It was found Impurity C was the major impurity that affected the quality of Escitalopram oxalate tablet. Stress test showed moisture and temperature were key factors in the formation of Impurity C. The content of Impurity C fomed in the developed process was 0.1% while the content of Impurity C formed in old process reached 0.2%, showing that process developed in the work produced less Impurity C than the old one did.4. Stablity tests under different temperatures were carried out and the results showed the product prepared by the developed process was more stable with the content of Impurity C kept around 0.2% after 18 months’test, while the content of Impurity C in the product prepared by old process can reach as high as 0.6%. Under 298.15 K and 313.15 K, the reaction kinetics of Impurity C for both developed and old processes were studied and the results showed that Impurity C increased linearly with time in both cases, indicating the fromation of Impurity C was a zero-order reaction. Calculated by Arrhenius Equation, the corresponding reaction activation energies for the old and developed process were 44,451 and 56,697 kJ/mol, respctively. Since the activation energies of the old process was smaller than that of the developed one, the product prepared by the developed process was more stable than that by the old one.The achievements of the work promoted the quality of Escitalopram oxalate tablet as well as enchanced the safity of the product.