YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Comparative Study on the Stability of Amoxicillin, Clavulanic Acid and its Commercial Combination Products

아목시실린, 클라불란 산 및 시판 아목시실린-클라불란 산 복합제제의 안전성 비교연구

  • Han, Sang-Dug (Research Center for New Drug Development, College of Pharmacy, Seoul National University) ;
  • Kim, Chong-Kook (Research Center for New Drug Development, College of Pharmacy, Seoul National University)
  • 한상덕 (서울대학교 약학대학 신의약품개발연구센터) ;
  • 김종국 (서울대학교 약학대학 신의약품개발연구센터)
  • Published : 2005.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, we evaluated the stability of amoxicillin (AMX) and clavulanic acid (CLA) in aqueous solution, and compared the stability of AMX and CLA in commercial combination products. In aqueous solutions, the degradation of AMX ($t_{90}=8.88\;day\;at\;10^{circ}C$) and CLA ($t_{90}=3.53\;day\;at\;10^{circ}C$) occurred rapidly. From the pH-rate profile, AMX and CLA were the most stable at the range of pH 5.5 and 6.0. After reconstitution of commercial dry syrups, the contents of AMX and CLA in suspensions were gradually decreased for 7 days. However, AMX and CLA in dispersible tablet were not changed at all. The contents of CLA in the dispersible tablet ($87.92\%$) and dry syrups (2.16 and $3.91\%$) were remained in the accel­erated stability test ($75\%\;RH,\;at\;40^{circ}C$) after 10 hours. And the colors of the dry syrups were rapidly changed from white to yellow. From these results, we concluded that the dispersible tablet could overcome the stability problems of dry syrups.

Keywords

References

  1. Gazi, H., Kurutepe, S., Surucuoglu, S., Teker, A. and Ozbakkaloglu, B. : Antimicrobial susceptibility of bacterial pathogens in the oropharynx of healthy school children in Turkey. Indian. J. Med. Res. 120, 489 (2004)
  2. Aurangzeb, B. and Hameed, A. : Comparative efficacy of amoxicillin, cefuroxime and clarithromycin in the treatment of community -acquired pneumonia in children. J. Coll. Physicians Surg. Pak. 13, 704 (2003)
  3. Neu, H. C. : The crisis in antibiotic resistance. Science 257, 1064 (1992) https://doi.org/10.1126/science.257.5073.1064
  4. Yang, Y., Rasmussen, B. A. and Shlaes, D. M. : Class A beta-lactamases--enzyme-inhibitor interactions and resistance. Pharmacol. Ther. 83, 141(1999) https://doi.org/10.1016/S0163-7258(99)00027-3
  5. Grant, E. B., Guiadeen, D., Baum, E. Z., Foleno, B. D., Jin, H., Montenegro, D. A., Nelson, E. A., Bush, K. and Hlasta, D. J. : The synthesis and SAR of rhodanines as novel class C beta-lactamase inhibitors. Med. Chem. Lett. 10, 2179 (2000) https://doi.org/10.1016/S0960-894X(00)00444-3
  6. Greenwood, D., Grady, F. O. and Baker, P. : An in vitro evaluation of clavulanic acid, a potent, broad-spectrum beta-lactamase inhibitor. J Antimicrob. Chemother. 5, 539 (1979) https://doi.org/10.1093/jac/5.5.539
  7. Reading, C. and Hepburn, P. : The inhibition of staphylococcal beta-Iactamase by clavulanic acid. Biochem. J. 179, 67(1979) https://doi.org/10.1042/bj1790067
  8. Reed, M. D. : Rational prescribing of extended-spectrum penicillin beta-lactamase inhibitor combinations: focus on ticarcillin/clavulanic acid. Ann. Pharmacother. 32, s17-s21 (1998) https://doi.org/10.1345/aph.17113
  9. Qadri, S. M. H., Ueno, Y. and Cunha, B. A. : Susceptibility of clinical isolates to expanded-spectrum beta-lactams alone and in the presence of beta-lactamase inhibitors. Chemotherarpy 42, 334 (1996) https://doi.org/10.1159/000239464
  10. Luzzaro, F., Perilli, M., Amicosante, G., Lombardi, G., Belloni, R., Zollo, A., Bianchi, C. and Toniolo, A. : Prevalence and characterization of metallo-beta-lactamases in clinical isolates of pseudomonas aeruginosa. Int. J. Antimicrob. Agents 17, 131 (2001) https://doi.org/10.1016/S0924-8579(00)00325-3
  11. Turck, M. : Clinical application of the newer beta-lactam antibiotics. J. Antimicrob. Chemother. 22, 45 (1988)
  12. Todd, P. A. and Benfield, P. : Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 39, 264 (1990) https://doi.org/10.2165/00003495-199039020-00008
  13. Miller, L. A., Ratnam, K. and Payne, D. J. : Beta-lactamase-inhibitor combinations in the 21st century: current agents and new developments. Curr. Opin. Pharmacol. 1, 451 (2001) https://doi.org/10.1016/S1471-4892(01)00079-0
  14. Lorenzo-Lamosa, M. L., Cuna, M., Vila-Jato, J. L., Toress, D. and Alonso, M. J. : Development of a microencapsulated form of cefuroxime axetil using pH-sensitive acrylic polymers. J. Microencap. 14, 607 (1997) https://doi.org/10.3109/02652049709006813
  15. Wildfeuer, A. and K. Rade, K. : Stability of ${\beta}$-lactamase inhibitors and ${\beta}$-lactam antibiotics in parenteral dosage forms and in body fluids and tissue homogenates: a comparative study of sulbactam, clavulanic acid, ampicillin and amoxicillin. Int. J. Antimicrob. Agents 6, 31 (1996) https://doi.org/10.1016/0924-8579(95)00017-3
  16. Shen, L., Lin, X., Xu, D. S. and Feng, Y. : Research progress on the oral solid rapidly disintegrating dosage form. Zhongguo Zhong Yao Za Zhi. 30, 89(2005)
  17. Kovarik, J. M., Noe, A., Berthier, S., McMahon, L., Langholff, W. K., Marion, A. S., Hoyer, P. F., Ettenger, R. and Rordorf, C. : Clinical development of an everolimus pediatric formulation: relative bioavailability, food effect, and steady-state pharmacokinetics. J. Clin. Pharmacol. 43, 141 (2003) https://doi.org/10.1177/0091270002239822
  18. Abounassif, M. A., Abdel-Moety, E. M., Mohamed, M. E. and Gad-Kariem, E. A. : Liquid chromatographic determination of amoxycillin and clavulanic acid in pharmaceutical preparations. J. Pharm. Biomed. Anal. 9, 731(1991) https://doi.org/10.1016/0731-7085(91)80214-T
  19. Cornors, K. A., Amidon, G. L. and Stella, V. J. : Chemical stability of pharmaceutics. A Handbook for Pharmacists, John Wiley & Sons Inc. (1986)
  20. Wells, J.I. : Pharmaceutical preformulation, Ellis Horwood Limited. (1988)
  21. Kim, C. K. and Cha, H. S. : Stability of pipethanate hydrochloride in aqueous solution. Arch. Pharm. Res. 4, 109 (1981) https://doi.org/10.1007/BF02855753
  22. Martin, A. : Physical Pharmacy fourth edition, p. 402 (1993)