In vitro stability of enoxaparin solutions (20 mg/mL) diluted in 4% glucose

Abstract

Background: Enoxaparin is an antithrombotic used for the prophylaxis of pediatric patients. Treatment can extend over weeks or months but there is no commercial pediatric dosage form of enoxaparin available. The stability of extemporaneously diluted enoxaparin, at pediatric dosage levels, has not been thoroughly evaluated. Therefore, pediatric doses are prepared extemporaneously on a daily basis, which results in subsequent limitations and problems.Objective: The aim of this study was to determine the stability of enoxaparin diluted with sterile water or 4% glucose solution over a 31-day period under different storage conditions.Methods: Enoxaparin (100 mg/mL) diluted with sterile water or extemporaneously prepared sterile 4% glucose to 20 mg/mL and undiluted enoxaparin (control) were kept at 4°C, -12°C, or -80°C. The antifactor Xa (AFXa) activity of stored solutions was determined by chromogenic assay on days 0, 7, 14, and 31 and was compared with the control solution.Results: Enoxaparin solution (20 mg/mL) diluted with 4% glucose lost 0.6%, 2.2%, and 9.6% of its initial AFXa activity after 31 days at 4°C, -12°C, and -80°C, respectively. Enoxaparin solution (20 mg/mL) diluted with water lost 10.0%, 12.4%, and 18.2% of its original AFXa activity at 4°C, -12°C, and -80°C after 31 days, respectively. Undiluted enoxaparin solution (100 mg/mL) lost 15.8% and 20.2% of its initial activity after 31 days at -12°C and -80°C, respectively, but no loss was detected at 4°C.Conclusions: Dilution of enoxaparin (100 mg/mL) with 4% glucose to 20 mg/mL and storage at 4°C preserved >99% of the initial AFXa activity after 31 days, compared with a loss of 10% of the initial activity in the enoxaparin solution diluted with water (to 20 mg/mL) and stored under the same conditions. Dilution with 4% glucose offers a potential method for the preparation of stable pediatric doses of enoxaparin.