KeywordsHealth Sciences, Pharmacy.
AdvisorYalkowsky, Samuel H.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractEptifibatide 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 dose, 10% ethanol, 40% propylene glycol and 50% 0.025 M citrate buffer. A carefully designed stability study was conducted in the pH range 4.25-6.25 under accelerated temperatures: 48°C, 60°C, 72.5°C. The results indicate that the proposed semi-aqueous vehicles greatly increased eptifibatide stability in comparison with aqueous vehicles. The pH-rate profiles of eptifibatide are V-shaped with the curves for semi-aqueous vehicles lower all over the test pH range. The pH of drug maximum stability is 5.25 in the aqueous vehicle, and it is shifted to 5.75 in the semi-aqueous vehicle. Studies indicate that eptifibatide degradation may involve a few different mechanisms: the specific acid catalyzed hydrolysis which is dominant in the acidic region, and a pH-dependent oxidation which is likely to be dominant in the basic region of the test pH range. The predicted drug shelf-life T90 at 25°C shows that an almost 2-fold increase can be achieved by formulating eptifibatide in the semi-aqueous vehicle, which is 60 months at its maximum stability pH 5.75 as opposed to the 33 months in the aqueous vehicle at its maximum stability pH 5.25.
Degree ProgramGraduate College