Stabilization of eptifibatide by cosolvents.
Eptifibatide is a potent and highly specific inhibitor of platelet receptor glycoprotein IIb/IIIa and is indicated in the treatment of acute coronary syndrome. The commercial product Integrilin(R) (eptifibatide) Injection requires a cold/refrigerator storage condition. In an effort to improve the drug stability for room temperature storage and transportation, this study proposed a semi-aqueous formulation that contains 2 mg/ml eptifibatide, 10% ethanol, 40% propylene glycol and 50% 0.025 M citrate buffer. The stability study was conducted in the pH range 4.25-6.25 under accelerated temperatures: 48, 60, 72.5 degrees C. The results indicate that the proposed semi-aqueous vehicles substantially increased the drug stability in comparison with aqueous vehicles. The predicted drug shelf-life T(90) at 25 degrees C shows that an almost twofold increase can be achieved by formulating eptifibatide in the semi-aqueous vehicle, which is 60 months at its maximum stability of pH 5.75, as opposed to the 33 months in the aqueous vehicle at its maximum stability of pH 5.25.
Zhao
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Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA.
Yalkowsky
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SH
D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D000077542:Eptifibatide; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D013696:Temperature
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D012997:Solvents; D000077542:Eptifibatide