Analysis of the Causes of Generation of Degradation Impurity Ⅰ of Loxoprofen Sodium Tablets
OBJECTIVE To study the factors affecting the generation of the degradation impurity 2-[(4-acetylphenyl)methyl]cyclopentanone(loxoprofen sodium impurity Ⅰ)in loxoprofen sodium tablets thus to provide reference for the formulation,preparation process and packaging design of loxoprofen sodium tablets.METHODS Stress testing of loxoprofen sodium and loxoprofen sodium tablets were carried out in conditions of high temperature(60 ℃),high humidity(92.5％RH)and strong light irradiation(4 500 lx).The compatibility test of loxoprofen sodium with excipients,and the content of impurity Ⅰ in bare tablets and different packages of loxoprofen sodium tablets were investigated under accelerated test conditions(50 ℃ and 75％RH).The content of impurity Ⅰ was determined by HPLC.RESULTS Loxoprofen sodium impurity Ⅰ is sensitive to humidity.High water content,moisture attracting and hydrophilic excipients such as calcium hydrogen phosphate,silicon dioxide and sodium starch glycolate might cause a significant increase of impurity Ⅰ.Moreover,there was incompatibility between mannitol and loxoprofen sodium,and the sealing performance of the package of aluminum plastic plate plus aluminum foil bag was better than that of the aluminum plastic plate package alone.CON-CLUSION In order to reduce the generation of potentially toxic impurity Ⅰ,the excipients of loxoprofen sodium tablets and the gran-ulation after drying should be controlled for water content.The use of aluminum plastic plate plus aluminum foil bag with better sealing performance can effectively reduce the generation of impurity Ⅰ.In addition,mannitol and loxoprofen sodium have compatibility prob-lems and should be avoided in the prescription.
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