Journal of Pharmaceutical Investigation Vol. 40, No. 6, 367-372 (2010) 367 Investigation of Degradation Mechanism of Rabeprazole with Solid State Pharmaceutical Excipients Shan Ren 1,3 , Thao Truong-Dinh Tran 1 , Phuong Ha-Lien Tran 1 , Yun-Seok Rhee 2 and Beom-Jin Lee 1† 1 Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea 2 School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Korea 3 Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, DENMARK (Received August 7, 2010·Revised November 26, 2010·Accepted November 27, 2010) ABSTRACT - 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 hydroxypro- pymethylcellulose (HPMC 4000) were also tested for comparison. The binary blends were stored under accelerated con- ditions (40 o 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 rabepra- zole as well as the relative peak area ratios obtained from FTIR spectra of S=O stretching at 1094.1 cm -1 decreased con- sistently 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 car- bomer 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 chro- matographic 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. Key words - Rabeprazole sodium, Thioether rabeprazole, Pharmaceutical excipients, Solid-state compatibility, Degra- dation mechanism In the preparation of solid dosage formulations, it is essential to combine drugs with pharmaceutical excipients as adjuvants. Pharmaceutical excipients are known to be key components in pharmaceutical dosage forms having a great impact on in vitro release and in vivo bioavailability of drugs (Serajuddin et al., 1999; Byrn et al., 2001; Bruni et al., 2004; Cornaire et al., 2004; Wang et al., 2004). Most of all, pharmaceutical excip- ients can affect the physicochemical stability of drugs in dos- age forms since they may function as stability enhancers or as promoters of the degradation of drugs (Loukas et al., 1998; Huang and Tong, 2004; Waterman and Adami, 2005; Urbanetz, 2006). Thus, rapid selection of pharmaceutical excipients for the evaluation of drug-excipient compatibility is essential at the early formulation approaches. Rabeprazole sodium, a benzimidazole class of proton-pump inhibitors (PPIs) has been used recently worldwide for healing, symptom relief and also for the prevention of relapse of acid- peptic diseases such as duodenal, gastric and esophageal ulcer- ation (Carswell and Goa, 2001). Rabeprazole is labile to acids and moisture but relatively stable under alkaline conditions (El-Gindy et al., 2002). At acidic or neutral pH, rabeprazole is converted non-enzymatically primarily to thioether rabepra- zole, resulting in the discoloration of drugs in solution as well as in solid-state (Richardson et al., 1998; Desta et al., 2002; Uno et al., 2005; Ren et al., 2008). Due to the pH sensitivity of drug in solution and solid-state, the selection of optimal pharmaceutical excipients with dif- ferent functional groups is crucial to maximize drug stability in the development of a stable dosage form of rabeprazole. Although the low stability of rabeprazole is reported under the acidic conditions, no detailed information on degradation behaviors of rabeprazole with pH dependent pharmaceutical excipients in a solid state is discussed yet. The purpose of this work was to compare chemical stability of RPN in a solid state binary blend with pharmaceutical excipients during the storage under accelerated conditions † Corresponding Author : Tel : +82-33-250-6919, E-mail : beomjinlee@gmail.com DOI : 10.4333/KPS.2010.40.6.367