Chiral Stability Study of Oral Liquid Clopidogrel Formulations for Infants

Abstract

ABSTRACTBackgroundClopidogrel is used in at‐risk infants to prevent thrombotic complications. There is no commercially available liquid preparation and existing formulations have not been evaluated for the chiral stability of clopidogrel.AimTo determine the stability of clopidogrel 1 mg/mL liquid formulations using chiral chromatography.MethodClopidogrel 1 mg/mL suspension was formulated using Plavix (clopidogrel) tablets and Ora‐Plus:Ora‐Sweet 1:1, and stored at room temperature and under refrigeration. Samples were also prepared using a variety of co‐solvents and stored at room temperature. Samples were taken for up to 49 days and assayed for S‐clopidogrel, R‐clopidogrel and S‐acid using high‐performance chiral liquid chromatography. Percentage of S‐clopidogrel remaining (at least 90% of nominal content) and percentage of degradation product formation were used to estimate shelf‐life.ResultsOnly the refrigerated Ora‐Plus:Ora‐Sweet mixture did not have degradation products that exceeded USP limits for clopidogrel impurities for at least 30 days. The estimated shelf‐lives of the Ora‐Plus:Ora‐Sweet mixtures at room temperature (25 °C) and under refrigeration (4 °C) were 19 and 37.5 days, respectively. There was no improvement in stability when mixtures were prepared using a variety of co‐solvents.ConclusionClopidogrel 1 mg/mL suspension made with Ora‐Plus:Ora‐Sweet and stored in amber glass bottles was stable for 1 month under refrigeration and 2 weeks at room temperature.