KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
권호 표지
DOI QR코드

DOI QR Code

Stability Improvement of Esomeprazole Magnesium Dihydrate Enteric-Coated Tablet by Adding Alkalizing Agents

에스오메프라졸 마그네슘 이수화물을 함유하는 장용성 제제의 안정성 개선

  • Cho, Young Ho (Department of Pharmaceutics & Biotechnology, Konyang University) ;
  • Jeon, Hyo Bin (Department of Pharmaceutics & Biotechnology, Konyang University) ;
  • Lee, Jong-Hwa (Toxicology Evaluation and Research Center, Korea Institute of Toxicology) ;
  • Lee, Gye Won (Department of Pharmaceutics & Biotechnology, Konyang University)
  • 조영호 (건양대학교 제약생명공학과) ;
  • 전효빈 (건양대학교 제약생명공학과) ;
  • 이종화 (안전성평가연구소 독성연구센터) ;
  • 이계원 (건양대학교 제약생명공학과)
  • Received : 2017.04.14
  • Accepted : 2017.06.02
  • Published : 2017.06.30
⟨ Previous Next ⟩

Abstract

Omeprazole, a benzimidazole derivative, suppresses gastric acid secretion by inhibiting $H^+/K^+$ ATPase in gastric parietals cells, and by reducing $H^+$ concentration. To improve stability of esomeprazole magnesium dihydrate (ESMD), enteric-coated preperation was composed of core tablet, subcoating and enteric coating layer. We were evaluated in vitro dissolution characteristics between test and reference ESMD preparation and stability. We could prepare enteric-coated formulation of ESMD by controlling disintegrating agent and coating ratio which could rapidly dissolved in neutral or alkali medium. The formulation D5 with crospovidone of 1.25% and coating ratio of 16.25% had a similar dissolution behavior compare to reference preparation. Difference factor ($f_1$) and similarity factor ($f_2$) were 0~15 and 50~100 and there was no significant difference in bioequivalence between formulations. The content and dissolution rate of formulation D5 were $96.54{\pm}0.21$ and $78.56{\pm}0.87%$ without change of color in accelerated condition ($40^{\circ}C$, RH 75%, high density polyethylene (HDPE) container) for 6 months. This study concluded that our enteric coated preparation of ESMD could be an useful method to improve stability of unstable drug without direct contact with coating material.

Keywords

References

  1. Goh, K. L. (2004) Changing epidermaology of gastro esophageal reflux disease in the Asian-Pacific region: An overview. J. Gasroenterol. Hepatol. 19: S22-S25. https://doi.org/10.1111/j.1440-1746.2004.03591.x
  2. Mullin, J. M., M. Gabello, L. J. Murray, C. P. Farrell, J. Bellows, K. R. Wolov, K. R. Kearney, D. Rudolph, and J. J. Thornton (2009) Proton pump inhibitors: actions and reactions. Drug Discov. Today 14: 647-660. https://doi.org/10.1016/j.drudis.2009.03.014
  3. Kim, J. H., J. G. Oh, G. S. Khang, J. K. Jeong, J. S. Lee, S. Y. Jeung and H. B. Lee (2002) The effect of sodium alginate coating on the storage stability and dissolution rate of enteric coated Lansoprazole. J. Kor. Pharm. Sci. 32: 277-284.
  4. Bisws, B. K., M. S. Islam, F. Begum, and A. S. S. Rouf (2008) In vitro release kinetic study of esomeprazole magnesium from methocel $K_{15}M$ and methocel $K_{100}$ LVCR matrix tablets. Dhaka Univ. J. Pharm. Sci. 7: 39-45.
  5. Richter, J. E., P. J. Kahrilas, J. Johanson, P. Maton, J. R. Breiter, C. Hwang, V. Marino, B. Hamelin, J. G. Levine (2001) Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am. J. Gastroenterol. 96: 656-665. https://doi.org/10.1111/j.1572-0241.2001.03600.x
  6. Kristl, A. and F. Vrecer (2000) Preformulation investigation of th novel proton pump inhibitor lansoprazole. Drug Dev. Ind. Pharm. 26: 781-783. https://doi.org/10.1081/DDC-100101299
  7. Baradell, L. B., D. Faulds, and D. McTavish (1992) Lansoprazole: A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders. Drugs. 44: 225-250. https://doi.org/10.2165/00003495-199244020-00007
  8. Jeong, S. H. (2007) The implication of incrementally modified drug technology and the current trends in psychopharmacology. Korean J. Psychopharmacol. 18: 373-383.
  9. Kim, J. J., S. Y. Lee, P. L. Rhee, S. J. Myung, J. H. Kim, M. Y. Gyu, S. Y. Kim, O. Y. Lee, J. S. Rew, Y. E. Joo, S. C. Choi, T. H. Kim, S. K. Kim, H. Y. Jeong, B. S. Lee, D. H. Kang, J. Y. Koo, and J. C. Rhee (2003) Multicenter study to evaluate the effect of esomeprazole in Gastro-esophageal reflux disease. Korean J. Neurogastroenterol. Motil. 9: 92-101.
  10. Pantoflickova, D., G. Dorta, M. Ravic, P. Jornod, and A. L. Blum (2003) Acid inhibition on the first day of dosing: comparison of proton pump inhibitors. Aliment Pharmacol. Ther. 17: 1507-1514. https://doi.org/10.1046/j.1365-2036.2003.01496.x
  11. Ia, H., H. Stenhoff, and M. Liljeblad (2007) Determination of esomeprazole and its two main metabolites in human, rat and dog plasma by liquid chromatography with tandem mass spectrometry. J. Chromatogra. B. Analyt. Technol. Biomed. Life Sci. 848: 317-322. https://doi.org/10.1016/j.jchromb.2006.10.074
  12. Andersson, T., M. Hassan-Alin, G. Hasselgren, and K. Rohss (2001) Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole. Clin. Pharmacokinet. 40: 523-537. https://doi.org/10.2165/00003088-200140070-00004
  13. Shim, C. K., Y. H. Han, J. S. Woo, and C. H. Lee (1993) Effect of arginine of sodium phosphate dibasic on the stability of omeprazole in aqueous solution. J. Kor. Pharm. 4: 225-229.
  14. Zhang, X., N. Sun, B. Wu, Y. Lu, T. Guan, and W. Wu (2008) Physical characterization of lansoprazole/PVP solid dispersion prepared by fluid-bed coating technique. Powder Technol. 182: 480-485. https://doi.org/10.1016/j.powtec.2007.07.011
  15. Ingmar, L. K., F. A. Gunnar, Y. Mitsuru, M. Satoshi, O. Minoru, and O. Naohiro (1987) Omeprazole preparation for oral use. KR Patent 19870004132.
  16. Tabata, T., T. Makino, J. Kikuta, S. Hirai, and N. Kitamori (1994) Manufacturing method of stable enteric granules of a new antiulcer drug (lansoprazole). Drug Dev. Ind. Pharm. 20: 1661-1672. https://doi.org/10.3109/03639049409050206
  17. Ho, H. O., H. L. Su, T. Tsai and M. T. Sheu (1996) The preparation and characterization of solid dispersions on pellets using a fluid bed system. Int. J. Pharm. 139: 223-229. https://doi.org/10.1016/0378-5173(96)04594-2
  18. US Pharmacopeia National Formulary (2003) USP 26-NF21. 3rd ed., pp. 2439. Mack Printing Company, Easton, USA.
  19. Ministry of Food and Drug Safety, Guideline on validation of analytical procedure. http://www.mfds.go.kr. (2015).
  20. Ministry of Food and Drug Safety, Guideline on bioequivalence test. http://nifds.go.kr. (2016).
  21. Yuksel, N., A. E. Kanik, and T. Baykara (2000) Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and -independent methods. Int. J. Pharm. 209: 57-67. https://doi.org/10.1016/S0378-5173(00)00554-8
  22. Moore, J. W. and H. H. Flanner (1996) Mathematical comparison of curves with an emphasis on in vitro dissolution profiles. Pharm. Tech. 20: 64-74.
  23. Shah, V. P., Y. Tsong, P. Sathe, and J. P. Liu (1998) In vitro dissolution profile comparison-statistics and analysis of similarity factor, f2. Pharm. Res. 15: 889-896. https://doi.org/10.1023/A:1011976615750
  24. Lee, Y. J., W. K. Whang, and S. W. Cho (2009) Effect of other medications on the stability of omeprazole in aqueous solution for the peptic ulcer disease. J. KAIS. 11: 3494-3499.
  25. Kim, Y. J. (1995) Stabilization of omeprazole by complexation with ethylenediamine. M.S. Thesis. Ewha Womans University, Seoul, Korea.
  26. Lee, E. J., K. D. Han, H. J. Shin, J. W. Kim and C. K. Kim (1997) Effect of L-arginine on the stability of omeprazole. J. Kor. Pharm. Sci. 27: 23-27
  27. Kumar, P. R., S. Shyale, M. M. Gouda, and S. M. S. Kumar (2011) Development of tablet formulation of enteric coated esomeprazole with Acrl EZE. Der Pharmacia Sinica. 2: 31-42.
  28. $Nexium^{(R)}$. http://www.rxlist.com/nexium-drug.htm. (2017).
  29. Yoon, Y. N., S. J. Kim, S. H. Jung, H. J. Kim, E. S. Park, S. J. Hwang, Y. W. Lee, H. S. Seong, B. C. Chin, and S. H. Cho (2009) Pharmacokinetic evaluation and gastric ulcer symptoms comparison of ketorolac tromethamine sustained release pellets after oral administration in beagle dogs. J. Pharm. Sci. 39: 401-409.
  30. Ministry of Food and Drug Safety, Guideline on stability test. http://nifds.go.kr. (2014).