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KMID : 0369820100400060367
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Jorunal of Korean Pharmaceutical Sciences
2010 Volume.40 No. 6 p.367 ~ p.372
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Investigation of Degradation Mechanism of Rabeprazole with Solid State Pharmaceutical Excipients
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Ren Shan
Tran Thao Truong Dinh
Tran Phuong Ha Lien
Rhee Yun-Seok
Lee Beom-Jin
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Abstract
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Rabeprazole sodium (RPN) is known to be very unstable at acidic condition or some acidic pharmaceutical excipients such as acrylic acid polymer (carbomer 934) with carboxylic acids. Thus, degradation mechanism of binary blends of rabeprazole with pharmaceutical excipients in a solid state without using solvents at three different ratios (3:1, 1:1 and 1:3) was investigated using Fourier transform infrad (FTIR) spectroscopy. Alkalizer (MgO), neutral ydroxypropymethylcellulose
(HPMC 4000) were also tested for comparison. The binary blends were stored under accelerated conditions (40o
C/75% relative humidity) for two weeks. The concentration of thioether rabeprazole from the binary blends with acidic carbomer 934 increased as the rabeprazole concentration decreased. In addition, the degradation half-life of rabeprazole
as well as the relative peak area ratios obtained from FTIR spectra of S=O stretching at 1094.1 cm-1 decreased consistently as the fraction of carbomer 934 increased due to its sensitivity between the basic benzimidazole nitrogen and
carboxylic acid group of carbomer 934. The physical appearance also turned into strong brown color in the presence of carbomer 934. In contrast, there were no significant changes in the degradation kinetics of rabeprazole with MgO and HPMC 4000 in a solid state. This present study demonstrated that the solid-state compatibility test with the aid of HPLC chromatographic and FTIR spectral analyses could offer a valuable methodology to select suitable pharmaceutical excipients and to elucidate the degradation mechanism of RPN for drug formulations at the early formulation stages.
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KEYWORD
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Rabeprazole sodium, Thioether rabeprazole, Pharmaceutical excipients, Solid-state compatibility, Degradation mechanism
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