Stability of levetiracetam in extemporaneously compounded suspensions

Abstract

Background: Levetiracetam is widely used as adjunctive therapy in the treatment of partial-onset seizures, myoclonic seizures, primary generalized tonic-clonic seizures, and idiopathic generalized epilepsy in the community and in hospital. However, no convenient, easy-to-swallow dosage form is commercially available in Canada. Moreover, no stability data are available for this antiepileptic prepared in a vehicle combining Ora-Sweet sweetener and Ora-Plus suspending agent. Objective: To evaluate the stability of levetiracetam suspensions in amber plastic bottles at room temperature and under refrigeration for up to 91 days. Methods: Suspensions of levetiracetam (50 mg/mL) were prepared in a 1:1 mixture of Ora-Sweet sweetening agent and Ora-Plus suspending agent. The suspensions were transferred to 50-mL amber plastic prescription bottles, which were stored at 25°C or at 4°C. Samples were collected from each bottle at time zero and on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, and 91. The samples were analyzed in triplicate by a validated, stability-indicating high-performance liquid chromatography method with ultraviolet detection. A suspension was considered stable if it maintained at least 90% of its initial concentration of levetiracetam. Colour, odour, taste, clarity, and pH were assessed to determine physical compatibility. Results: All samples remained physically unchanged over time, and there was no significant change in pH. The 95% confidence interval of the slope of the curve relating concentration to time, determined by linear regression, indicated that suspensions stored at 25°C would maintain at least 91.4% of the initial levetiracetam concentration for 91 days and that suspensions stored at 4°C would maintain at least 93.2% of the initial concentration for 91 days, with 95% confidence. Conclusion: Levetiracetam suspensions prepared in Ora-Sweet/Ora-Plus vehicle and stored in plastic prescription bottles at either 25°C or 4°C can be expected to remain stable for 91 days.