Skip to main content
SpringerLink
Log in

In situ intestinal permeability and in vivo oral bioavailability of celecoxib in supersaturating self-emulsifying drug delivery system

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

In order to characterize the in situ intestinal permeability and in vivo oral bioavailability of celecoxib (CXB), a poorly water-soluble cyclooxygenase (COX)-2 inhibitor, various formulations including the self-emulsifying drug delivery system (SEDDS) and supersaturating SEDDS (S-SEDDS) were compared. The S-SEDDS formulation was obtained by adding Soluplus as a precipitation inhibitor to SEDDS, composed of Capryol 90 as oil, Tween 20 as surfactant, and Tetraglycol as cosurfactant (1:4.5:4.5 in volume ratio). An in situ single pass intestinal perfusion study in rats was performed with CXB-dissolved solutions at a concentration of 40 μg/mL. The effective permeability (Peff) of CXB in the control solution (2.5 v/v% Tween 20-containing PBS) was 6.39 × 10−5 cm/s. The Peff value was significantly increased (P < 0.05) by the lipid-based formulation, yielding 1.5- and 2.9-fold increases for the SEDDS and S-SEDDS solutions, respectively, compared to the control solution. After oral administration of various formulations to rats at the equivalent dose of 100 mg/kg of CXB, the plasma drug level was measured by LC–MS/MS. The relative bioavailabilities of SEDDS and S-SEDDS were 263 and 355 %, respectively, compared to the CXB suspension as a reference. In particular, S-SEDDS revealed the highest Cmax and the smallest Tmax, indicating rapid and enhanced absorption with this formulation. This study illustrates the potential use of the S-SEDDS formulation in the oral delivery of poorly water-soluble compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Amidon, G.L., H. Lennernas, V.P. Shah, and J.R. Crison. 1995. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research 12: 413–420.

    Article  CAS  PubMed  Google Scholar 

  • Arai, H., M. Murata, and J. Shinoda. 1971. The interaction between polymer and surfactant: the composition of the complex between polyvinylpyrrolidone and sodium alkyl sulfate as revealed by surface tension, dialysis, and solubilization. Journal of Colloid and Interface Science 37: 223–227.

    Article  CAS  Google Scholar 

  • Attwood, D., and A.T. Florence. 1983. Surfactant systems: their chemistry, pharmacy and biology. New York: Chapman and Hall.

    Book  Google Scholar 

  • Berggren, S., J. Hoogstraate, U. Fagerholm, and H. Lennernas. 2004. Characterization of jejunal absorption and apical efflux of ropivacaine, lidocaine and bupivacaine in the rat using in situ and in vitro absorption models. European Journal of Pharmaceutical Sciences 21: 553–560.

    Article  CAS  PubMed  Google Scholar 

  • Brouwers, J., M.E. Brewster, and P. Augustijns. 2009. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? Journal of Pharmaceutical Sciences 98: 2549–2572.

    Article  CAS  PubMed  Google Scholar 

  • Brusewitz, C., A. Schendler, A. Funke, T. Wagner, and R. Lipp. 2007. Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of active compounds. International Journal of Pharmaceutics 329: 173–181.

    Article  PubMed  Google Scholar 

  • Charman, S.A., W.N. Charman, M.C. Rogge, T.D. Wilson, F.J. Dutko, and C.W. Pouton. 1992. Self-emulsifying drug delivery systems: formulation and bio-pharmaceutical evaluation of an investigational lipophilic compound. Pharmaceutical Research 9: 87–93.

    Article  CAS  PubMed  Google Scholar 

  • Chen, L., X. Sha, X. Jiang, Y. Chen, Q. Ren, and X. Fang. 2013. Pluronic P105/F127 mixed micelles for the delivery of docetaxel against Taxol resistant non-small cell lung cancer: optimization and in vitro, in vivo evaluation. International Journal of Nanomedicine 8: 73–84.

    PubMed Central  PubMed  Google Scholar 

  • Chiou, W.L., and A. Barve. 1998. Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharmaceutical Research 15: 1792–1795.

    Article  CAS  PubMed  Google Scholar 

  • Clemett, D., and K.L. Goa. 2000. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs 59: 957–980.

    Article  CAS  PubMed  Google Scholar 

  • de Vries, N.A., J. Zhao, E. Kroon, T. Buckle, J.H. Beijnen, and O. van Tellingen. 2007. P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clinical Cancer Research 13: 6440–6449.

    Article  PubMed  Google Scholar 

  • Dressman, J.B., and C. Reppas. 2000. In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. European Journal of Pharmaceutical Sciences 11: S73–S80.

    Article  CAS  PubMed  Google Scholar 

  • Fagerholm, U., M. Johansson, and H. Lennernas. 1996. Comparison between permeability coefficients in rat and human jejunum. Pharmaceutical Research 13: 1336–1342.

    Article  CAS  PubMed  Google Scholar 

  • Gao, P., B.D. Rush, W.P. Pfund, T. Huang, J.M. Bauer, W. Morozowich, M.S. Kuo, and M.J. Hageman. 2003. Development of a supersaturable SEDDS(S-SEDDS) formulation of paclitaxel with improved oral bioavailability. Journal of Pharmaceutical Sciences 92: 2386–2398.

    Article  CAS  PubMed  Google Scholar 

  • Gursoy, R.N., and S. Benita. 2004. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomedicine & Pharmacotherapy 58: 173–182.

    Article  Google Scholar 

  • Guzman, H.R., M. Tawa, Z. Zhang, P. Ratanabanangkoon, P. Shaw, C.R. Gardner, H. Chen, J.P. Moreau, O. Almarsson, and J.F. Remenar. 2007. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. Journal of Pharmaceutical Sciences 96: 2686–2702.

    Article  CAS  PubMed  Google Scholar 

  • Hillgren, K.M., A. Kato, and R.T. Borchardt. 1995. In vitro systems for studying intestinal drug absorption. Medicinal Research Reviews 15: 83–109.

    Article  CAS  PubMed  Google Scholar 

  • Jones, M.N. 1968. Dye solubilization by a polymer-surfactant complex. Journal of Colloid and Interface Science 26: 532–533.

    Article  CAS  Google Scholar 

  • Kang, M.J., H.S. Kim, H.S. Jeon, J.H. Park, B.S. Lee, B.K. Ahn, K.Y. Moon, and Y.W. Choi. 2012. In situ intestinal permeability and in vivo absorption characteristics of olmesartan medoxomil in self-microemulsifying drug delivery system. Drug Development and Industrial Pharmacy 38: 587–596.

    Article  CAS  PubMed  Google Scholar 

  • Khan, K.A., and C.T. Rhodes. 1975. The concept of dissolution efficiency. Journal of Pharmacy and Pharmacology 27: 48–49.

    Article  CAS  PubMed  Google Scholar 

  • Karlsson, J., and P. Artursson. 1991. A method for the determination of cellular permeability coefficients and aqueous boundary layer thickness in monolayers of intestinal epithelial (Caco-2) cells grown in permeable filter chambers. International Journal of Pharmaceutics 71: 55–64.

    Article  CAS  Google Scholar 

  • Komiya, I., J.Y. Park, A. Kamani, N.F.H. Ho, and W.I. Higuchi. 1980. Quantitative mechanistic studies in simultaneous fluid flow and intestinal absorption using steroids as model solutes. International Journal of Pharmaceutics 4: 249–262.

    Article  CAS  Google Scholar 

  • Lennernas, H., O. Ahrenstedt, R. Hallgren, L. Knutson, M. Ryde, and L.K. Paalzow. 1992. Regional jejunal perfusion, a new in vivo approach to study oral drug absorption. Pharmaceutical Research 9: 1243–1251.

    Article  CAS  PubMed  Google Scholar 

  • Linn, M., E.M. Collnot, D. Djuric, K. Hempel, E. Fabian, K. Kolter, and C.M. Lehr. 2012. Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. European Journal of Pharmaceutical Sciences 45: 336–343.

    Article  CAS  PubMed  Google Scholar 

  • O’driscoll, C.M., and B.T. Griffin. 2008. Biopharmaceutical challenges associated with drugs with low aqueous solubility—the potential impact of lipid-based formulations. Advanced Drug Delivery Reviews 60: 617–624.

    Article  PubMed  Google Scholar 

  • Paulson, S.K., M.B. Vaughn, S.M. Jessen, Y. Lawal, C.J. Gresk, B. Yan, T.J. Maziasz, C.S. Cook, and A. Karim. 2001. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. Journal of Pharmacology and Experimental Therapeutics 297: 638–645.

    CAS  PubMed  Google Scholar 

  • Pouton, C.W. 2006. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. European Journal of Pharmaceutical Sciences 29: 278–287.

    Article  CAS  PubMed  Google Scholar 

  • Rubas, W., N. Jezyk, and G.M. Grass. 1993. Comparison of the permeability characteristics of a human colonic epithelial (Caco-2) cell line to colon of rabbit, monkey, and dog intestine and human drug absorption. Pharmaceutical Research 10: 113–118.

    Article  CAS  PubMed  Google Scholar 

  • Saito, S. 1967. Solubilization properties of polymer-surfactant complexes. Journal of Colloid and Interface Science 24: 227–234.

    Article  CAS  Google Scholar 

  • Salphati, L., K. Childers, L. Pan, K. Tsutsui, and L. Takahashi. 2001. Evaluation of a single-pass intestinal-perfusion method in rat for the prediction of absorption in man. Journal of Pharmacy and Pharmacology 53: 1007–1013.

    Article  CAS  PubMed  Google Scholar 

  • Shah, N.H., M.T. Carvajal, C.I. Patel, M.H. Infeld, and A.W. Malick. 1994. Self-emulsifying drug delivery systems with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. International Journal of Pharmaceutics 106: 15–23.

    Article  CAS  Google Scholar 

  • Shakeel, F., S. Baboota, A. Ahuja, J. Ali, M. Aqil, and S. Shafiq. 2007. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech 8: 191–199.

    Article  PubMed Central  Google Scholar 

  • Song, W.H., J.H. Park, D.W. Yeom, B.K. Ahn, K.M. Lee, S.G. Lee, H.S. Woo, and Y.W. Choi. 2013. Enhanced dissolution of celecoxib by supersaturating self-emulsifying drug delivery system (S-SEDDS) formulation. Archives of Pharmacal Research 36: 69–78.

    Article  CAS  PubMed  Google Scholar 

  • Subramanian, N., S. Ray, S.K. Ghosal, R. Bhadra, and S.P. Moulik. 2004. Formulation design of self-microemulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biological and Pharmaceutical Bulletin 27: 1993–1999.

    Article  CAS  PubMed  Google Scholar 

  • Swenson, E.S., and W.J. Curatolo. 1992. Intestinal permeability enhancement for proteins, peptides and other polar drugs: mechanisms and potential toxicity. Advanced Drug Delivery Reviews 8: 39–92.

    Article  CAS  Google Scholar 

  • Ullah, I., M.K. Baloch, and G.F. Durrani. 2011. Solubility of nonsteroidal anti-inflammatory drugs (NSAIDs) in aqueous solution of non-ionic surfactants. Journal of Solution Chemistry 40: 1341–1348.

    Article  CAS  Google Scholar 

  • Vasconcelos, T., B. Sarmento, and P. Costa. 2007. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discovery Today 12: 1068–1075.

    Article  CAS  PubMed  Google Scholar 

  • Yao, J., Y. Lu, and J.P. Zhou. 2008. Preparation of nobiletin in self-microemulsifying systems and its intestinal permeability in rats. Journal of Pharmacy and Pharmaceutical Sciences 11: 22–29.

    CAS  PubMed  Google Scholar 

  • Zakeri-Milani, P., M. Barzegar-Jalali, H. Tajerzadeh, Y. Azarmi, and H. Valizadeh. 2005. Simultaneous determination of naproxen, ketoprofen and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. Journal of Pharmaceutical and Biomedical Analysis 39: 624–630.

    Article  CAS  PubMed  Google Scholar 

  • Zakeri-Milani, P., H. Valizadeh, H. Tajerzadeh, Y. Azarmi, Z. Islambolchilar, S. Barzergar, and M. Barzegar-Jalali. 2007. Predicting human intestinal permeability using single-pass intestinal perfusion in rat. Journal of Pharmacy and Pharmaceutical Sciences 10: 368–379.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the Chung-Ang University Research Scholarship Grants in 2013.

Author information

Authors and Affiliations

  1. Drug Delivery Research Laboratory, College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul, 156-756, Korea

    Woo Heon Song, Dong Woo Yeom, Dong Hoon Lee, Kyung Min Lee, Hyun Joon Yoo, Bo Ram Chae, Seh Hyon Song & Young Wook Choi

Authors
  1. Woo Heon Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong Woo Yeom
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dong Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyung Min Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hyun Joon Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bo Ram Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seh Hyon Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Young Wook Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Wook Choi.

Additional information

W. H. Song and D. W. Yeom have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, W.H., Yeom, D.W., Lee, D.H. et al. In situ intestinal permeability and in vivo oral bioavailability of celecoxib in supersaturating self-emulsifying drug delivery system. Arch. Pharm. Res. 37, 626–635 (2014). https://doi.org/10.1007/s12272-013-0202-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-013-0202-7

Keywords

Search

Navigation