Stability of Valproate Sodium Syrup in Various Unit Dose Containers

Abstract

The stability of valproate sodium syrup repackaged in three types of unit dose containers was studied. Two-millimeter samples of commercial valproate sodium syrup 250 mg/5 ml (of valproic acid) were packaged in polypropylene oral syringes, glass oral syringes, and glass vials (126 of each type). These were stored at 4, 25, or 60 degrees C and assayed for valproic acid concentration using gas chromatography at 0, 5, 10, 20, 30, 90, and 180 days. Polypropylene syringes that were stored for 180 days at 4 and 25 degrees C were rinsed and put in chloroform 50 ml; valproic acid concentration was determined daily for 12 days. Valproate sodium syrup repackaged in glass oral syringes and glass vials retained 95% of valproic acid label claim after storage at 4 and 25 degrees C for 180 days, while valproate sodium syrup repackaged in polypropylene oral syringes did not retain 90% of label claim after storage for 20 days at 4 or 25 degrees C. All samples stored at 60 degrees C had greater loss than those stored at lower temperatures. An average of 86% of the drug lost from the polypropylene syringes was recovered in 12 days during the desorption experiment (range 80-92%). Repackaging valproate sodium syrup in unit dose glass vials or glass syringes resulted in retention of 95% of valproic acid label claim after storage for 180 days at 4 and 25 degrees C. Repackaging of this drug product in polypropylene oral syringes is not recommended.