Stability of a compounded oral liquid formulation of clopidogrel for infants

Abstract

AbstractBackgroundClopidogrel is recommended to prevent thrombotic complications in at‐risk infants. No commercial liquid formulation is currently available. Published compounded liquid formulations have not accounted for chiral instability at recommended storage conditions, and studied strengths are problematic in measuring accurate doses for infants.AimThis study examined the stability of a low strength (1 mg/mL) oral liquid formulation of clopidogrel using a chiral chromatographic method to separate active S‐clopidogrel from its predominant degradation product R‐clopidogrel, as well as its acid products.MethodsClopidogrel mixtures (1 mg/mL) prepared using Plavix tablets (Sanofi‐Aventis, Macquarie Park, NSW, Australia) in 1 : 1 Ora‐Plus : Ora‐Sweet (Perrigo, Minneapolis, MN, USA) were stored at room temperature (25°C) and under refrigeration (4°C). Samples stored were assayed periodically for S‐clopidogrel using chiral liquid chromatography to a minimum of 55 days. The percentage of S‐clopidogrel remaining (at least 90% of nominal content) was used to estimate shelf life. Physical and microbiological stability was also assessed.ResultsEstimated shelf lives at room temperature and under refrigeration were 12 and 46 days, respectively. When removed from refrigeration, kept at 25°C for 3 days and then returned to the refrigerator, the shelf life was reduced to 41 days. Physical stability was maintained during these periods, and there was no evidence of microbiological contamination.ConclusionIt is recommended that clopidogrel 1 mg/mL in an oral preparation containing Ora‐Plus : Ora‐Sweet be stored in the refrigerator (4°C) and discarded 6 weeks after compounding. If removed from the refrigerator to room temperature (25°C) for 3 days, so long as the suspension is returned to the refrigerator, it could be used at a reduced shelf life of 1 month.