Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Investigation of Degradation Mechanism of Rabeprazole with Solid State Pharmaceutical Excipients

  • Ren, Shan (Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University) ;
  • Tran, Thao Truong-Dinh (Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University) ;
  • Tran, Phuong Ha-Lien (Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University) ;
  • Rhee, Yun-Seok (School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Beom-Jin (Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University)
  • Received : 2010.08.07
  • Accepted : 2010.11.27
  • Published : 2010.12.20
Download PDF
⟨ Previous Next ⟩

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 hydroxypropymethylcellulose (HPMC 4000) were also tested for comparison. The binary blends were stored under accelerated conditions ($40^{\circ}C$/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.

Keywords

References

  1. Bommareddy, G.S., Paker-Leggs, S., Saripella, K.K., Neau, S.H., 2006. Extruded and spheronized beads containing Carbopol 974P to deliver nonelectrolytes and salts of weakly basic drugs. Int. J. Pharm. 321, 62-71. https://doi.org/10.1016/j.ijpharm.2006.05.017
  2. Bruni, G., Amici, L., Berbenni, V., Marini, A., Orlandi, A., 2002. Drug-excipient compatibility studies. Search of interaction indicators. J. Therm. Anal. Cal. 68, 561-573. https://doi.org/10.1023/A:1016052121973
  3. Byrn, S.R., Xu, W., Newman, A.W., 2001. Chemical reactivity in solid-state pharmaceuticals: formulation implications. Adv. Drug Deliv. Rev. 48, 115-136. https://doi.org/10.1016/S0169-409X(01)00102-8
  4. Carswell, C., Goa, K., 2001. Rabeprazole: An update of its use in acid-related disorders. Drugs 61, 2327-2356. https://doi.org/10.2165/00003495-200161150-00016
  5. Cornaire, G., Woodley, J., Hermann, P., Cloarec, A., Arellano, C., Houin, G., 2004. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int. J. Pharm. 278, 119-131. https://doi.org/10.1016/j.ijpharm.2004.03.001
  6. Desta, Z., Zhao, X., Shin, J.G., Flockhart, D.A., 2002. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin. Pharmacokinet. 41, 913-958. https://doi.org/10.2165/00003088-200241120-00002
  7. El-Gindy, A., El-Yazby, F., Maher, M.M., 2003. Spectrophotometric and chromatographic determination of rabeprazole in presence of its degradation products. J. Pharm. Biomed. Anal. 31, 229-242. https://doi.org/10.1016/S0731-7085(02)00445-4
  8. Fujioka, T., Kawasaki, H., Su, W.W., Nasu, M., 1993. In vitro anti microbial activity against H. pylori and clinical efficacy of various drugs. Jpn. J. Clin. Med. 51, 3255-3260.
  9. Gaisford, S., 2005. Stability assessment of pharmaceuticals and biopharmaceuticals by isothermal calorimetry. Curr. Pharm. Biotechnol. 6, 181-191. https://doi.org/10.2174/1389201054022913
  10. Huang, L.F., Tong, W.Q., 2004. Impact of solid state properties on developability assessment of drug candidates. Adv. Drug Deliv. Rev. 56, 321-334. https://doi.org/10.1016/j.addr.2003.10.007
  11. Karabas, I., Orkoula, M.G., Kontoyannis, C.G., 2007. Analysis and stability of polymorphs in tablets: the case of risperidone. Talanta 71, 1382-1386. https://doi.org/10.1016/j.talanta.2006.07.009
  12. Loukas, Y.L., Vraka, V., Gregoriadis, G., 1998. Drugs, in cyclodextrins, in liposomes: a novel approach to the chemical stability of drugs sensitive to hydrolysis. Int. J. Pharm. 162, 137-142. https://doi.org/10.1016/S0378-5173(97)00421-3
  13. Morii, M., Takata, H., Fujisaki, H., Takeguchi, N., 1990. The potency of substituted benzimidazoles such as E3810, omeprazole, RO 18-5364 to inhibit gastric $H^{+},K^{+}$-ATPase is correlated with the rate of acid-activation of the inhibitor. Biochem. Pharmacol. 39, 661-667. https://doi.org/10.1016/0006-2952(90)90143-9
  14. Neugebauer, H., Brabec, C.J., Hummelen, J.C., Janssen, R.A.J., Sariciftci, N.S., 1999. Stability studies and degradation analysis of plastic solar cell materials by FTIR spectroscopy. Synth. Metals 102, 1002-1003. https://doi.org/10.1016/S0379-6779(98)01184-9
  15. Richardson, P., Hawkey, C.J., Stack, W.A., 1998. Proton pump inhibitors: pharmacology and rationale for use in gastrointestinal disorders. Drugs 56, 307-335. https://doi.org/10.2165/00003495-199856030-00002
  16. Rowe, R.C., Sheskey, P.J., Weller, P.J., 2003. Handbook of Pharmaceutical Excipients, 4th ed. Pharmaceutical Press, London, UK.
  17. Serajuddin, A.T., Thakur, A.B., Ghoshal, R.N., Fakes, M.G., Ranadive, S.A., Morris, K.R., Varia, S.A., 1999. Selection of solid dosage form composition through drug-excipient compatibility testing. J. Pharm. Sci. 88, 696-704. https://doi.org/10.1021/js980434g
  18. Tutunji, M.F., Qaisi, A.M., El-Eswed, B., Tutunji, L.F., 2006. An in vitro investigation on acid catalyzed reactions of proton pump inhibitors in the absence of an electrophile. Int. J. Pharm. 323, 110-116. https://doi.org/10.1016/j.ijpharm.2006.05.057
  19. Uno, T., Yasui-Furukori, N., Shimizu, M., Sugawara, K., Tateishi, T., 2005. Determination of rabeprazole and its active metabolite, rabeprazole thioether in human plasma by columnswitching high-performance liquid chromatography and its application to pharmacokinetic study. J. Chromatogr. B 824, 238-243. https://doi.org/10.1016/j.jchromb.2005.07.027
  20. Urbanetz, N.A., 2006. Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000. Eur. J. Pharm. Sci. 28, 67-76. https://doi.org/10.1016/j.ejps.2005.12.009
  21. Verma, R.K, Garg, S., 2005. Selection of excipients for extended release formulations of Glipizide through drug-excipient compatibility testing. J. Pharm. Biomed. Anal. 38, 633-644. https://doi.org/10.1016/j.jpba.2005.02.026
  22. Wang, S.W., Monagle, J., McNulty, C., Putnam, D., Chen, H., 2004. Determination of P-glycoprotein inhibition by excipients and their combinations using an integrated high-throughput process. J. Pharm. Sci. 93, 2755-2767. https://doi.org/10.1002/jps.20183
  23. Waterman, K.C., Adami, R.C., 2005. Accelerated aging: Prediction of chemical stability of pharmaceuticals. Int. J. Pharm. 293, 101-125. https://doi.org/10.1016/j.ijpharm.2004.12.013
  24. Wong, L.H.G., Sung, J.Y.J., 2006. Esomeprazole: a new proton pump inhibitor for NSAID-associated peptic ulcers and dyspepsia. Therapy 3, 227-236. https://doi.org/10.2217/14750708.3.2.227
  25. Wyttenbach, N., Birringer, C., Alsenz, J., Kuentz, M., 2005. Drug-excipient compatibility testing using a high-throughput approach and statistical design. Pharm. Dev. Technol. 10, 499-505. https://doi.org/10.1080/10837450500299875
  26. Zhang, Y., Chen, X., Gu, Q., Zhong, D., 2004. Quantification of rabeprazole in human plasma by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta 523, 171-175. https://doi.org/10.1016/j.aca.2004.07.023