Stabilization of eptifibatide by cosolvents

Luwei Zhao, Samuel H Yalkowsky

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43-56
Number of pages14
JournalInternational Journal of Pharmaceutics
Volume218
Issue number1-2
DOIs
StatePublished - May 7 2001

Fingerprint

Drug Stability
Platelet Membrane Glycoproteins
Propylene Glycol
Platelet Glycoprotein GPIIb-IIIa Complex
Temperature
Acute Coronary Syndrome
Citric Acid
Buffers
Ethanol
eptifibatide
Injections
Therapeutics

Keywords

  • Cosolvents
  • Eptifibatide
  • Integrilin
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Stabilization of eptifibatide by cosolvents. / Zhao, Luwei; Yalkowsky, Samuel H.

In: International Journal of Pharmaceutics, Vol. 218, No. 1-2, 07.05.2001, p. 43-56.

Research output: Contribution to journalArticle

@article{0b33015479904783a4865960b00147f6,
title = "Stabilization of eptifibatide by cosolvents",
abstract = "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{\circledR} (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.",
keywords = "Cosolvents, Eptifibatide, Integrilin, Stability",
author = "Luwei Zhao and Yalkowsky, {Samuel H}",
year = "2001",
month = "5",
day = "7",
doi = "10.1016/S0378-5173(01)00618-4",
language = "English (US)",
volume = "218",
pages = "43--56",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Stabilization of eptifibatide by cosolvents

AU - Zhao, Luwei

AU - Yalkowsky, Samuel H

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 -