Shelf-life Prediction Of Esomeprazole Magnesium Enteric-coated Tablets

The shelf-life of a drug product is most-often determined based on the time when that product,in its packaging,remains safe and effective while stored under defined temperature and relative humidity conditions.In order to determine the stability of the drug product as soon as possible,researchers often use accelerated and stress stability data to predict shelf life of pharmaceuticals.In this study,we applied a variety of prediction methods to predict the shelf-life of esomeprazole magnesium enteric-coated tablets.Meanwhile,the two indicators of active ingredient content and impurity content were examined and the prediction results were compared with the long-term test results.Under the temperature conditions,the content of impurity No.1 was used as the test index.Classical isothermal kinetic method,t_0.2method,gray model,and multivariate linear model were used to predict the shelf-life of the drug.The obtaining equations for the four prediction models were as follows:lnk=-12161.908/T+31.045,lgt_0.2=5114.544/T-12.748,lnt=11877.919/T-29.619,lnt=-28.630+11637.858/T+1.061×ln（lgc-lgc₀）.The expiration dates of esomeprazole magnesium enteric-coated tablets by four different methods were 21.1 months,18.3 months,19.6 months,17.9 months.Under the temperature conditions,the active ingredient content as the test index.Classical isothermal kinetic method,t_0.95method,and multivariate linear model method were used to predict the shelf-life of the drug,the obtaining equations for three prediction models were as follows:lnk=-13015.169/T+25.187,lgt_0.95=5900.282/T-14.863,lnt=-25.498+12843.467/T+0.894×ln（1/c-1/c₀）.The expiration dates of esomeprazole magnesium enteric-coated tablets by three different methods were 37.0 months,54.9 months,45.3 months.Under the temperature and humidity conditions,the content of impurity No.1 was used as the test indexes.Humidity-corrected Arrhenius model method was used to predict the shelf-life of the drug.The equations for the prediction model was as follows:ln（1/t）=-16824.430/T+0.013RH+45.260.The predicted shelf-life was 36.0 months.We used actual 18-month long-term test results to verify the validity prediction model.The preliminary judgment was that the prediction model obtained by using humidity-corrected Arrhenius equation（the content of impurity No.1 was used as the test index）agreed well with the actual 18-month long-term test results.