TY - JOUR
T1 - Stabilization of eptifibatide by cosolvents
AU - Zhao, Luwei
AU - Yalkowsky, Samuel H.
N1 - Funding Information:
We would like to thank Cor Therapeutics Inc. for funding of this research.
PY - 2001/5/7
Y1 - 2001/5/7
N2 - 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® (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°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 T90 at 25°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.
AB - 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® (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°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 T90 at 25°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.
KW - Cosolvents
KW - Eptifibatide
KW - Integrilin
KW - Stability
UR - http://www.scopus.com/inward/record.url?scp=0035821417&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035821417&partnerID=8YFLogxK
U2 - 10.1016/S0378-5173(01)00618-4
DO - 10.1016/S0378-5173(01)00618-4
M3 - Article
C2 - 11337148
AN - SCOPUS:0035821417
VL - 218
SP - 43
EP - 56
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -