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Stabilization of eptifibatide by cosolventsZhao, Luwei January 2000 (has links)
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 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.
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BIOSYNTHESIS OF L-AZETIDINE-2-CARBOXYLIC ACID IN ACTINOPLANES FERRUGINEUSLEE, KANG MAN. January 1985 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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ANALYTICAL AND METABOLIC STUDIES OF MITOTANE AND ITS ANALOGUESRUANGWISES, NONGLUCK. January 1990 (has links)
Thesis (Ph. D.)--University OF MICHIGAN. / CHAIRMAN: JOSEPH E. SINSHEIMER.
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QUANTITATIVE MECHANISTIC STUDIES OF ZONAL TRANSPORT AND METABOLISM IN THE HEPATIC ACINUSCHEN, ELINOR HUEI-LING. January 1982 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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SELECTED STUDIES ON THE BARRIER PROPERTIES OF SKINGOVIL, SHARAD KUMAR. January 1984 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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ESTERASE HYDROLYSIS OF AN HOMOLOGOUS SERIES OF PABA ESTERS IN HAIRLESS MOUSE AND HUMAN SKIN HOMOGENATESWITHAM, SANDRA LYNN CHANEY. January 1989 (has links)
Thesis (Ph. D.)--University OF MICHIGAN. / CO-CHAIRMEN: JENNIFER B. DRESSMAN; GORDON L. FLYNN.
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INVESTIGATION INTO DRUG AND DRUG ANALOGS TRANSPORTED BY THE PEPTIDE CARRIER SYSTEM: INTESTINAL ABSORPTION OF CAPTOPRIL AND OF PEPTIDYL DERIVATIVES OF METHYLDOPAHU, MING. January 1988 (has links)
Thesis (Ph. D.)--University OF MICHIGAN. / CHAIRMAN: GORDON L. AMIDON.
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THE MECHANISM OF ACTION OF SOLUTION FLUORIDE UPON THE DEMINERALIZATION RATE OF ENAMELMIR, NASIM AKHTAR, January 1967 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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LIPOSOMES AS A POTENTIAL ORAL DRUG DELIVERY SYSTEMCHIANG, CHIA-MING. January 1900 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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SOLID-STATE STUDIES ON THE POLYMORPHS OF METHYLPREDNISOLONEMUNSHI, MAYANK VIRENDRA. January 1973 (has links)
Thesis (Ph. D.)--University OF MICHIGAN.
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