Archives of Pharmacal Research

, Volume 32, Issue 5, pp 767–772 | Cite as

Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution

  • Young-Joon Park
  • Ram Kwon
  • Qi Zhe Quan
  • Dong Hoon Oh
  • Jong Oh Kim
  • Ma Ro Hwang
  • Yoon Bon Koo
  • Jong Soo Woo
  • Chul Soon Yong
  • Han-Gon Choi
Research Articles Drug Actions

Abstract

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.

Key words

Solid dispersion Ibuprofen Solubility Pharmacokinetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Charoenchaitrakool, M., Dehghani, F., and Foster, N. R., Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-beta-cyclodextrin. Int. J. Pharm., 239, 103–112 (2002).CrossRefPubMedGoogle Scholar
  2. Chiou, W. L. and Riegelman, S., Pharmaceutical application of solid dispersion systems. J. Pharm. Sci., 73, 1281–1303 (1971).CrossRefGoogle Scholar
  3. Choi, H. G., Lee, B. J., Yong, C. S., Rhee, J. D., Han, J. H., Lee, M. K., Park K. M., and Kim, C. K., Terfenadine-β-cyclodextrin inclusion complex with the anti-histaminic activity enhancement. Drug Dev. Ind. Pharm., 27, 857–862 (2001).CrossRefPubMedGoogle Scholar
  4. 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 (1998).CrossRefGoogle Scholar
  5. Craig, D. Q. M., The mechanism of drug release from solid dispersion in water-soluble polymers. Int. J. Pharm., 231, 131–144 (2002).CrossRefPubMedGoogle Scholar
  6. Gerrnhalgh, D. J., Williams, A. C., Timmins, P., and York, P., Solubility parameters as predictors of miscibility in solid dispersions. J. Pharm. Sci., 88, 1182–1190 (1999).CrossRefGoogle Scholar
  7. Ghorab, M. K. and Adeyeye, M. C., Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin, Pharm. Dev. Technol., 6, 305–314 (2001).CrossRefPubMedGoogle Scholar
  8. Ghosh, L. K., Ghosh, N. C., Chatterjee, M., and Gupta, B. K., Product development studies on the tablet formulation of ibuprofen to improve bioavailability. Drug Dev. Ind. Pharm., 24, 473–477 (1998).CrossRefPubMedGoogle Scholar
  9. Glowka, F. K., Stereoselective pharmacokinetics of ibuprofen and its lysinate from suppositories in rabbits. Int. J. Pharm., 199, 159–166 (2000).CrossRefPubMedGoogle Scholar
  10. Greenhalgh, D. J., Williams, A. C., Timmins, P., York, P., Solubility parameters as predictors of miscibility in solid dispersions. J. Pharm. Sci., 88, 1182–1190 (1999).CrossRefPubMedGoogle Scholar
  11. Kachrimanis, K., Nikolakakis, I., and Malamataris, S., Spherical crystal agglomeration of ibuprofen by the solventchange technique in presence of methacrylic polymers. J. Pharm. Sci., 89, 250–259 (2000).CrossRefPubMedGoogle Scholar
  12. Khan, G. M. and Jiabi, Z., Preparation, characterization, and dissolution studies of ibuprofen solid dispersions using polyethylene glycol (PEG), talc, and PEG-talc as dispersion carriers. Drug Dev. Ind. Pharm., 24, 455–462 (1998).CrossRefPubMedGoogle Scholar
  13. Kim, C. K., Choi, J. Y., Yoon, Y. S., Gong, J. P., Choi, H. G., Kong, J. Y., and Lee, B. J., Preparation and evaluation of dry elixir for the enhancement of dissolution rate of poorly water-soluble drugs. Int. J. Pharm., 106, 25–32 (1997).Google Scholar
  14. Leuner, C. and Dressman, J., Improving drug solubility for oral delivery using solid dispersions. Eur. J. Pharm. Biopharm., 50, 47–60 (2000).CrossRefPubMedGoogle Scholar
  15. Li, D. X., Oh, Y. K., Lim, S. J., Kim, J. O, Yang, H. J., Sung, J. H., Yong, C. S., and Choi, H. G., Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray drying technique. Int. J. Pharm., 355, 277–284 (2008).CrossRefPubMedGoogle Scholar
  16. Murtha, J. L. and Ando, H. Y., Synthesis of the cholesteryl ester prodrugs cholesteryl ibuprofen and cholesteryl flufenamate and their formulation into phospholipid microemulsions. J. Pharm. Sci., 83, 1222–1228 (1994).CrossRefPubMedGoogle Scholar
  17. Newa, M., Bhandari, K. H., Li, D. X., Kim, J. O, Yoo, D. S., Kim, J. A., Yoo, B. K., Woo, J. S., Lyoo, W. S., Yong, C. S., and Choi, H. G., Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000. Biol. Pharm. Bull., 31, 939–945 (2008).CrossRefPubMedGoogle Scholar
  18. Newa, M., Bhandari, K. H., Li, D. X., Kwon, T. H., Kim, J. A., Yoo, B. K., Woo, J. S., Lyoo W. S., Yong, C. S., Choi, H. G., Preparation, characterization and in vivo evaluation of ibuprofen binary solid diseprsion with poloxamer 188. Int. J. Pharm., 243, 228–237 (2007).CrossRefGoogle Scholar
  19. Passerini, N., Gonzalez-Rodriguez, M. L., Cavallari, C., Rodriguez, L., and Albertini, B., Preparation and characterisation of ibuprofen-poloxamer 188 granules obtained by melt granulation. Eur. J. Pharm. Sci., 15, 71–78 (2002).CrossRefPubMedGoogle Scholar
  20. Rasenack, N. and Muller, B. W., Dissolution rate enhance-ment by in situ micronization of poorly water-soluble drugs. Pharm. Res., 19, 1894–1900 (2002 a).CrossRefPubMedGoogle Scholar
  21. Rasenack, N. and Muler, B. W., Properties of ibuprofen crystallized under various conditions: A comparative study. Drug Dev. Ind. Pharm., 28, 1077–1089 (2002 b).CrossRefPubMedGoogle Scholar
  22. Seo, A., Holm, P., Kristensen, H. G., and Schæfer, T., The preparation of agglomerates containing solid dispersions of diazepam by melt agglomeration in a high shear mixer, Int. J. Pharm., 259, 161–171 (2003).CrossRefPubMedGoogle Scholar
  23. Society of Toxicology (SOT). Guilding Priciples in the Use of Animals in Toxicology, www.toxicology.org/AI/FA/guidingprinciples.pdf, (1999).
  24. Taylor, L. S. and Zografi, G., Spectroscopic characterization interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm. Res., 14, 1691–1698 (1997).CrossRefPubMedGoogle Scholar
  25. Yamashita, K., Nakate, T., Okimoto, K., Ohike, A., Tokunaga, Y., Ibuki, R., Higaki, K., and Kimura, T., Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int. J. Pharm., 267, 79–91 (2003).CrossRefPubMedGoogle Scholar
  26. Yong, C. S., Lee, M. K., Park, Y. J., Kong, K. H., Xuan, J. J., Kim, J. H., Kim, J. A., Lyoo, W. S., Han, S. S., Rhee, J. D., Kim, J. O., Yang, C. H., Kim, C. K., and Choi, H. G., Enhanced oral bioavailability of ibuprofen in rats by poloxamer gel using poloxamer 188 and menthol. Drug Dev. Ind. Pharm., 31, 615–622 (2005).CrossRefPubMedGoogle Scholar
  27. Yong, C. S., Yang, C. H., Rhee, J. D., Lee, B. J., Kim, D. C., Kim, D. D., Kim, C. K., Choi, J. S., and Choi H. C., Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol. Int. J. Pharm., 269, 169–176 (2004).CrossRefPubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2009

Authors and Affiliations

  • Young-Joon Park
    • 2
  • Ram Kwon
    • 1
  • Qi Zhe Quan
    • 3
  • Dong Hoon Oh
    • 1
  • Jong Oh Kim
    • 1
  • Ma Ro Hwang
    • 1
  • Yoon Bon Koo
    • 2
  • Jong Soo Woo
    • 1
  • Chul Soon Yong
    • 2
  • Han-Gon Choi
    • 1
  1. 1.College of PharmacyYeungnam UniversityGyongsanKorea
  2. 2.Research CenterSamil Pharmaceutical Co. Ltd.AnsanKorea
  3. 3.Biochemical Engineering CollegeBeijing Union UniversityBeijingChina

Personalised recommendations