The AAPS Journal

, Volume 9, Issue 3, pp E344–E352 | Cite as

Preparation and in vivo evaluation of SMEDDS (self-microemulsifying drug delivery system) containing fenofibrate

  • Ashok R. Patel
  • Pradeep R. VaviaEmail author


The present work was aimed at formulating a SMEDDS (self-microemulsifying drug delivery system) of fenofibrate and evaluating its in vitro and in vivo potential. The solubility of fenofibrate was determined in various vehicles. Pseudoternary phase diagrams were used to evaluate the microemulsification existence area, and the release rate of fenofibrate was investigated using an in vitro dissolution test. SMEDDS formulations were tested for microemulsifying properties, and the resultant microemulsions were evaluated for clarity, precipitation, and particle size distribution. Formulation development and screening was done based on results obtained from phase diagrams and characteristics of resultant microemulsions. The optimized formulation for in vitro dissolution and pharmacodynamic studies was composed of Labrafac CM10 (31.5%), Tween 80 (47.3%), and polyethylene glycol 400 (12.7%). The SMEDDS formulation showed complete release in 15 minutes as compared with the plain drug, which showed a limited dissolution rate. Comparative pharmacodynamic evaluation was investigated in terms of lipid-lowering efficacy, using a Triton-induced hypercholesterolemia model in rats. The SMEDDS formulation significantly reduced serum lipid levels in phases I and II of the Triton test, as compared with plain fenofibrate. The optimized formulation was then subjected to stability studies as per International Conference on Harmonization (ICH) guidelines and was found to be stable over 12 months. Thus, the study confirmed that the SMEDDS formulation can be used as a possible alternative to traditional oral formulations of fenofibrate to improve its bioavailability.


Fenofibrate SMEDDS pseudoternary phase diagrams Triton-induced hyperlipidemia 


  1. 1.
    Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci. 2000; 11: S93-S98.PubMedCrossRefGoogle Scholar
  2. 2.
    Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995; 12: 1561–1572.PubMedCrossRefGoogle Scholar
  3. 3.
    Kim HJ, Yoon KA, Hahn M, Park ES, Chi SC. Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone. Drug Dev Ind Pharm. 2000; 26: 523–529.PubMedCrossRefGoogle Scholar
  4. 4.
    Kang BK, Lee JS, Chona SK, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm. 2004; 274: 65–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying drug delivery systems (SEDDS) with polyglycolysed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm. 1994; 106: 15–23.CrossRefGoogle Scholar
  6. 6.
    Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ, Pouton CW. Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm Res. 1992; 9: 87–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001; 212: 233–246.PubMedCrossRefGoogle Scholar
  8. 8.
    Physician’s Desk Reference 2000. 54th ed. Montvale, NJ: Medical Economics Company; 2000: 476–477.Google Scholar
  9. 9.
    Kasim NA, Whitehouse M, Ramachandran C, et al. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm. 2004; 1: 85–96.PubMedCrossRefGoogle Scholar
  10. 10.
    Patel AR, Vavia PR. Effect of hydrophilic polymer on solubilization of fenofibrate by cyclodextrin complexation. J Incl Phenom Macrocycl Chem. 2006; 56: 247–251.CrossRefGoogle Scholar
  11. 11.
    Law D, Wang W, Schmitt E, Qiu Y, Krill SK, Fort JJ. Properties of rapidly dissolving eutectic mixtures of poly(ethylene glycol) and fenofibrate: the eutectic microstructure. J Pharm Sci. 2003; 92: 505–515.PubMedCrossRefGoogle Scholar
  12. 12.
    Curtet B, Teillaud E, Reginault P, inventors. Fournier Innovation et Synergie, assignee. Novel dosage form of fenofibrate. US patent 4 895 726. January 23, 1980.Google Scholar
  13. 13.
    Tricor. fenofibrate [package insert]. North Chicago, IL: Abbott Laboratories. 2002.Google Scholar
  14. 14.
    Khoo SM, Humberstone AJ, Porter CJ, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm. 1998; 167: 155–164.CrossRefGoogle Scholar
  15. 15.
    Zlatkis A, Zak B, Boyle AJ. New method for direct determination of serum cholesterol. J Lab Clin Med. 1953; 41: 486–492.PubMedGoogle Scholar
  16. 16.
    Foster IB, Dunn RT. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method. Clin Chem. 1973; 19: 338–340.PubMedGoogle Scholar
  17. 17.
    Groves MJ. The self-emulsifying action of mixed surfactants in oil. Acta Pharm Suec. 1976; 13: 361–372.PubMedGoogle Scholar
  18. 18.
    Schulman JH, Montagne JB. Formation of microemulsions by amino alkyl alcohols. Ann N Y Acad Sci. 1961; 92: 366–371.PubMedCrossRefGoogle Scholar
  19. 19.
    Mei X, Etzler FM, Wang Z. Use of texture analysis to study hydrophilic solvent effects on the mechanical properties of hard gelatin capsules. Int J Pharm. 2006; 324: 128–135.PubMedCrossRefGoogle Scholar
  20. 20.
    Gao ZG, Choi HG, Shin HJ, et al. Physicochemical characterization and evaluation of a microemulsion system for oral delivery of cyclosporin A. Int J Pharm. 1998; 161: 75–86.CrossRefGoogle Scholar
  21. 21.
    Constantinides PP, Scalart JP. Formulation and physical characterization of water-in-oil microemulsions containing long-versus medium-chain glycerides. Int J Pharm. 1997; 158: 57–68.CrossRefGoogle Scholar
  22. 22.
    de Campo L, Yaghmur A, Garti N, Leser ME, Folmer B, Glatter O. Five-component food-grade microemulsions: structural characterization by SANS. J Colloid Interface Sci. 2004; 274: 251–267.PubMedCrossRefGoogle Scholar
  23. 23.
    Szekeres E, Acosta E, Sabatini DA, Harwell JH. A two-state model for selective solubilization of benzene-limonene mixtures in sodium dihexyl sulfosuccinate microemulsions. Langmuir. 2004; 20: 6560–6569.PubMedCrossRefGoogle Scholar
  24. 24.
    Nutting DF, Tso P. Hypolipidemic effects of intravenous pluronic L-81 in fasted rats treated with Triton WR-1339; possible inhibition of hepatic lipoprotein secretion. Horm Metab Res. 1989; 21: 113–115.PubMedCrossRefGoogle Scholar
  25. 25.
    Schurr PE, Schultz JR, Parkinson TM. Triton-induced hyperlipidemia in rats as an animal model for screening hypolipidemic drugs. Lipids. 1972; 7: 68–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Krishnamurthy A, Thapar GS. Effect of benzafibrate and nicotinic acid on Triton-induced hyperlipidemias in CFY rats. Indian J Med Res. 1991; 94: 395–398.PubMedGoogle Scholar
  27. 27.
    Mahley RW, Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw Hill; 2006: 957–958.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  1. 1.Centre for Novel Drug Delivery Systems, Department of Pharmaceutical SciencesUniversity Institute of Chemical TechnologyMumbalIndia

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