water / oil emulsion composition with gauge oil droplets, method for doing the same and method for treating a patient in need of a single high dose of clopidogrel

摘要

The present disclosure provides ready-to-use, oil/water emulsion compositions with mean droplet size (intensity-average, m) of 100-500 nm, wherein the oil phase comprises clopidogrel free base dispersed in pharmaceutical acceptable oil(s). The emulsion uses clopidogrel free base or premix of clopidogrel free base in oil(s) as the starting materials and may also contain one or more excipients such as surfactant and or co-surfactant, osmotic agent, pH adjustment agent, antioxidant, preservative, sweetener, and/or suspending agent, etc. The emulsion formulations and method of manufacturing significantly improves the stability of clopidogrel over other aqueous based formulations (such as cyclodextrin-based formulations and emulsion made using clopidogrel salt as the starting materials) with respect to chiral degradation, hydrolytic, and thermal degradation. Ready-to-use emulsion compositions, which can be administered orally or parentally as a single high dose with up to 300 mg of clopidogrel dose, can be prepared and stored at room temperature for at least 19 weeks or at refrigeration temperature for at least 1 year. The compositions will provide rapid therapeutic action as anti-platelet agent for patient under emergence and intense care or who cannot swallow tablet dosage form.