Advertisement

Archives of Pharmacal Research

, Volume 26, Issue 2, pp 162–167 | Cite as

Physicochemical characterization andin vivo evaluation of thermosensitive diclofenac liquid suppository

  • Yong Chul Soon
  • Choi Young-Kwon
  • Kim Yong-II
  • Park Byung-Joo
  • Quan Qi-Zhe
  • Rhee Jong-Dai
  • Kim Chong-Kook
  • Choi Han-GonEmail author
Research Articles Articles

Abstract

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

Key words

Diclofenac sodium Sodium chloride Liquid suppository Thermosensitive Pharmacokinetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson, B. D. and Conradi, R. A., Predictive relationships in the water solubility of salts of a nonsteroidal anti-inflammatory drug.J. Pharm. Sci., 74, 815–820 (1985).PubMedCrossRefGoogle Scholar
  2. Choi, H. G. and Kim, C. K., Development of omeprazole buccal adhesive tablets with stability enhancement in human saliva.J. Control Rel., 68, 397–404 (2000).CrossRefGoogle Scholar
  3. Choi, H. G., Jung, J. H., Ryu, J. M., Yoon, S. J., Oh, Y. K., and Kim, C. K., Development of in-situ gelling and mucoadhesive acetaminophen liquid suppository.Int. J. Pharm., 165, 33–44 (1998a).CrossRefGoogle Scholar
  4. Choi, H. G., Jung, J. H., Yong, C. S., Rhee, J. D., Lee, M. K., Han, J. H., Park, K. M., and Kim, C. K., Formulation and in vivo evaluation of omeprazole buccal adhesive tablet.J. Control Rel., 68, 405–412 (2000).CrossRefGoogle Scholar
  5. Choi, H. G., Kim, M. H., Lee, M. K., and Kim, C. K., Effect of additives on the physicochemical properties of liquid suppository.Int. J. Pharm., 190, 13–19 (1999).PubMedCrossRefGoogle Scholar
  6. Choi, H. G., Oh, Y. K., and Kim, C. K.,In-situ gelling and mucoadhesive liquid suppository containing acetaminophen: enhanced bioavailability.Int. J. Pharm., 165, 23–32 (1998b).CrossRefGoogle Scholar
  7. Dumortier, G., Zumer, M., Courarraze, G., Chaumeil, J. C., and Grossiord, J. L., Rheological study of a thermoreversible morphine gel.Drug Dev. Ind. Pharm., 17, 1255–1265 (1991).CrossRefGoogle Scholar
  8. Garcia, M. S., Albero, M. I., Sanchez-Pedreno, C., and Molina, J., Flow-injection spectrophotometric determination of diclofenac sodium in pharmaceuticals and urine samples.J. Pharm. Biomed. Anal., 17 (2), 267–273 (1998).PubMedCrossRefGoogle Scholar
  9. Huang, C. H., Tokumura, T., Machida, Y., and Nagai, T., Formulation of double-layered suppository for prolonged stay in lower rectum.Yakuzaigaku, 47, 42–48 (1987).Google Scholar
  10. Idkaidek, N. M., Amidon, G. L., Smith, D. E., Najib, N. M., and Hassan, M. M., Determination of the population pharmacokinetic parameters of sustained-release and enteric-coated oral formulations, and the suppository formulation of diclofenac sodium by simultaneous data fitting using NONMEM.Bio-pharm. Drug Dispos., 19 (3), 169–174 (1998).CrossRefGoogle Scholar
  11. Iwata, M., Takayama, K., Takahashi, Y., Obata, Y., Machida, Y., Nagai, T., and Shirotake, S., Effect of temperature on drug release and drug absorption in mixed type diclofenac sodium suppositories.Yakugaku Zasshi (Japan), 119, 170–177 (1999).Google Scholar
  12. Kramaric, A., Resman, A., Kofler, B., and Zmitek, J., Thermoreversible gel as a liquid pharmaceutical carrier for a galenic formulation.European Patent, 0551 626 (A1) (1992).Google Scholar
  13. Miyazaki, S., Nakamura, T., and Takada, M., Thermo-sensitive sol-gel transition of Pluronic F-127.Yakuzaigaku, 51, 36–43 (1991).Google Scholar
  14. Miyazaki, S., Nakamura, T., Yokouchi, C., and Tanaka, M., Effect of pluronic gels on the rectal absoption of indomethacin in rabbits.Chem. Pharm. Bull., 35, 1243–1248 (1987).PubMedGoogle Scholar
  15. Miyazaki, S., Suisha, F., Kawasaki, N., Shirakawa, M., Yamatoya, K., and Attwood, Thermally reversible xyloglucan gels as vehicles for rectal drug delivery.J. Control Rel., 56, 75–83 (1998).CrossRefGoogle Scholar
  16. Nakanishi, K., Masukawa, T., Masada, M., and Nadai, T., Improvement of the rectal bioavailability of latamoxef sodium by adjuvants following administration of a suppository.Biol. Pharm. Bull., 17, 1496–1500 (1994).PubMedGoogle Scholar
  17. Pinto-Pereira, L. M., Chen, D., Clement, Y., Simeon, D., Analgesic effects of diclofenac suppository and injection after preoperative administration.Int. J. Clin. Pharmacol. Res., 19(2), 47–51 (1999).PubMedGoogle Scholar
  18. Ramakrishna, S., Fadnavis, N. W., and Diwan, P. V., Comparative pharmacokinetic evaluation of compressed suppositories of diclofenac sodium in humans.Arzneimittelforschung, 46, 175–177 (1996).PubMedGoogle Scholar
  19. Schneeweis, A. and Muller-Goymann, C. C.,In vivo andin vitro diclofenac sodium evaluation after rectal application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) for controlled release.Pharm. Res., 14, 1726–1729 (1997).PubMedCrossRefGoogle Scholar
  20. Yun, M. O., Choi, H. G., Jung, J. H. and Kim, C. K., Development of thermoreversible insulin liquid suppository with sodium salicylate.Int. J. Pharm., 189, 137–145 (1999).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2003

Authors and Affiliations

  • Yong Chul Soon
    • 1
  • Choi Young-Kwon
    • 2
  • Kim Yong-II
    • 1
  • Park Byung-Joo
    • 1
  • Quan Qi-Zhe
    • 1
  • Rhee Jong-Dai
    • 1
  • Kim Chong-Kook
    • 3
  • Choi Han-Gon
    • 1
    Email author
  1. 1.College of PharmacyYeungnam UniversityGyongsanKorea
  2. 2.Icure Pharmaceutical Corp. Research Institute of Advanced materials 412Seoul National UniversitySeoulKorea
  3. 3.College of PharmacySeoul National UniversitySeoulKorea

Personalised recommendations