Skip to main content
SpringerLink
Log in

In vitro and in vivo evaluation of a self-microemulsifying drug delivery system for the poorly soluble drug fenofibrate

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

Abstract

Fenofibrate is indicated in hypercholesterolemia and hypertriglyceridemia alone or combined (types IIa, IIb, III, IV, and V dyslipidemias). However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery system (SMEDDS). We used pseudoternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution and bioavailability assessment consisted of propylene glycol laurate (Lauroglycol FCC) (60 %), macrogol-15-hydroxystearate (Solutol HS 15) (27 %), and diethylene glycol monoethyl ether (Transcutol-P) (13 %). The mean droplet size of the oil phase in the microemulsion formed by the SMEDDS was 131.1 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. In vivo pharmacokinetics study of fenofibrate in beagles administered SMEDDS-A form resulted in a 3.7-fold increase in bioavailability as compared with the reference drug. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • 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 biopharmaceutic evaluation of an investigational lipophilic compound. Pharmaceutical Research 9: 87–93.

    Article  CAS  PubMed  Google Scholar 

  • Chi, S.C. 1999. Enhanced dissolution rate of biphenyl dimethyl dicarboxylate using SMEDDS. Bulletin Technique Gattefossé 92: 75–80.

    Google Scholar 

  • Constantinides, P.P. 1995. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharmaceutical Research 12: 1561–1572.

    Article  CAS  PubMed  Google Scholar 

  • Craig, D.M.Q. 1993. The use of self-emulsifying systems as a means of improving drug delivery. Bulletin Technique Gattefossé 86: 21–31.

    CAS  Google Scholar 

  • Curtet B, Teillaud E, Reginault P (1980) inventors. Fournier Innovation et Synergie, assignee. Novel dosage form of fenofibrate. US patent 4895726., January 23.

  • Danielsson, I., and B. Lindman. 1981. The definition of microemulsion. Colloids and Surfaces 3: 391–392.

    Article  CAS  Google Scholar 

  • Georgakopoulos, E., N. Farah, and G. Vergnault. 1992. Oral anhydrous nonionic microemulsions administrated in softgel capsules. Bulletin Technique Gattefossé 85: 11–20.

    Google Scholar 

  • Gershanik, T., S. Benzeno, and S. Benita. 1998. Interaction of a self-emulsifying lipid drug delivery system with the inverted rat intestinal mucosa as a function of droplet size and surface charge. Pharmaceutical Research 15: 863–869.

    Article  CAS  PubMed  Google Scholar 

  • Groves, M.J., and D.A. de Galindez. 1976. The self-emulsifying action of mixed surfactants in oil. Acta Pharmaceutica Suecica 13: 361–372.

    CAS  PubMed  Google Scholar 

  • Guay, D.R. 2002. Update on fenofibrate. Cardiovascular Drug Reviews 20: 281–302.

    Article  CAS  PubMed  Google Scholar 

  • Hanafy, A., H. Spahn-Langguth, G. Vergnault, P. Grenier, M. Tubic Grozdanis, T. Lenhardt, and P. Langguth. 2007. Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug. Advanced Drug Delivery Reviews 59: 419–426.

    Article  CAS  PubMed  Google Scholar 

  • Kang, B.K., J.S. Lee, S.K. Chon, S.Y. Jeong, S.H. Yuk, G. Khang, H.B. Lee, and S.H. Cho. 2004. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. International Journal of Pharmaceutics 274: 65–73.

    Article  CAS  PubMed  Google Scholar 

  • Kasim, N.A., M. Whitehouse, C. Ramachandran, M. Bermejo, H. Lennernäs, A.S. Hussain, H.E. Junginger, S.A. Stavchansky, K.K. Midha, V.P. Shah, and G.L. Amidon. 2004. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Molecular Pharmaceutics 1: 85–96.

    Article  CAS  PubMed  Google Scholar 

  • Kawakami, K., T. Yoshikawa, Y. Moroto, E. Kanaoka, K. Takahashi, Y. Nishihara, and K. Masuda. 2002. Microemulsion formulation for enhanced absorption of poorly soluble drugs. I. Prescription design. Journal of Controlled Release 81: 65–74.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H.J., K.A. Yoon, M. Hahn, E.S. Park, and S.C. Chi. 2000. Preparation and in vitro evaluation of self microemulsifying drug delivery systems containing idebenone. Drug Development and Industrial Pharmacy 26: 523–529.

    Article  CAS  PubMed  Google Scholar 

  • Kim, K.H., Y.S. Rhee, J.H. Bae, S.C. Chi, and E.S. Park. 1999. Improvement of dissolution rate of poorly water soluble drug using self-microemulsifying drug delivery system. Journal of Korean Pharmaceutical Sciences 29: 37–45.

    CAS  Google Scholar 

  • Kreuter, J. (ed.). 1997. Colloidal drug delivery systems, 31–65. New York: Marcel Dekker.

    Google Scholar 

  • Korea (2007) Food and Drug Administration, K-BE Test 2007 and BA Calc.

  • Law, D., W. Wang, E.A. Schmitt, Y. Qiu, S.L. Krill, and J.J. Fort. 2003. Properties of rapidly dissolving eutectic mixtures of poly(ethylene glycol) and fenofibrate: the eutectic microstructure. Journal of Pharmaceutical Sciences 92: 505–515.

    Article  CAS  PubMed  Google Scholar 

  • Mayer, D. 1988. Surfactant science and technology, 174–175. New York: VCH Publishers, Inc.

    Google Scholar 

  • Najib, J. 2002. Fenofibrate in the treatment of dyslipidemia: a review of the data as they relate to the new suprabioavailable tablet formulation. Clinical Therapeutics 24: 2022–2050.

    Article  CAS  PubMed  Google Scholar 

  • Patel, A.R., and P.R. Vavia. 2006. Effect of hydrophilic polymer on solubilization of fenofibrate by cyclodextrin complexation. Journal of Inclusion Phenomena and Macrocyclic Chemistry 56: 247–251.

    Article  CAS  Google Scholar 

  • Physician’s Desk Reference (2000) 54th ed Medical Economics Company, Montvale, NJ. 476–477.

  • Porter, C.J.H., A.M. Kaukonen, B.J. Boyd, G.A. Edwards, and W.N. Charman. 2004. Susceptibility to lipase-mediated digestion reduces the oral bioavailability of danazol after administration as a medium-chain lipid-based microemulsion formulation. Pharmaceutical Research 21: 1405–1412.

    Article  CAS  PubMed  Google Scholar 

  • Pouton, C.W. 2000. Lipid formulations for oral administration of drugs: nonemulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. European Journal of Pharmaceutical Sciences 11: S93–S98.

    Article  CAS  PubMed  Google Scholar 

  • Sarciaux, J.M., L. Acar, and P.A. Sado. 1995. Using microemulsion formulations for oral drug delivery of therapeutic peptides. International Journal of Pharmaceutics 120: 127–136.

    Article  CAS  Google Scholar 

  • Schulman, J.H., and J.B. Montagne. 1961. Formation of microemulsions by amino alkyl alcohols. Annals of the New York Academy of Sciences 92: 366–371.

    Article  CAS  PubMed  Google Scholar 

  • Schulman, J.H., W. Stoekenius, and L.M.J. Prince. 1959. Mechanism of formation and structure of micro emulsions by electron microscopy. Journal of Physical Chemistry 63: 1677–1678.

    Article  CAS  Google Scholar 

  • Shah, N.H., M.T. Carvajal, C.I. Patel, M.H. Infeld, and A.W. Malick. 1994. Selfemulsifying drug delivery systems (SEDDS) 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 

  • Torrado, S., M.L. Lopez, G. Torrado, F. Bolas, S. Torrado, and R. Cadorniga. 1997. A novel formulation of albendazole solution: oral bioavailability and efficacy evaluation. International Journal of Pharmaceutics 156: 181–187.

    Article  CAS  Google Scholar 

  • TriCor (2002) (fenofibrate) [package insert]. Abbott Laboratories, North Chicago, IL.

  • Vetter, R.D., M.C. Carey, and J.S. Patton. 1985. Coassimilation of dietary fat and benzo(a)pyrene in the small intestine: an absorption model using the killifish. Journal of Lipid Research 26: 428–434.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Research Institute CJ Cheiljedang, 522-1, Deokpyeong-ri, Majang-myeong, Gyeonggi-do, Icheon-si, Korea

    Young-Dae Cho & Young-Joon Park

Authors
  1. Young-Dae Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young-Joon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young-Joon Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cho, YD., Park, YJ. In vitro and in vivo evaluation of a self-microemulsifying drug delivery system for the poorly soluble drug fenofibrate. Arch. Pharm. Res. 37, 193–203 (2014). https://doi.org/10.1007/s12272-013-0169-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-013-0169-4

Keywords

Search

Navigation