AAPS PharmSciTech

, 20:129 | Cite as

Self-Emulsifying Oral Lipid Drug Delivery Systems: Advances and Challenges

  • Sarita Rani
  • Rafquat Rana
  • Gaurav K. Saraogi
  • Vipin Kumar
  • Umesh GuptaEmail author
Review Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Part of the following topical collections:
  1. Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery


The attempts to oral delivery of lipids can be challenging. Self-emulsifying drug delivery system (SEDDS) plays a vital role to tackle this problem. SEDDS is composed of an oil phase, surfactants, co-surfactants, emulsifying agents, and co-solvents. SEDDS can be categorized into self-nano-emulsifying agents (SNEDDS) and self-micro-emulsifying agents (SMEDDS). The characterization of SEDDS includes size, zeta potential analysis, and surface morphology via electron microscopy and phase separation methods. SEDDS can be well characterized through different techniques for size and morphology. Supersaturation is the phenomenon applied in case of SEDDS, in which polymers and copolymers are used for SEDDS preparation. A supersaturated SEDDS formulation kinetically and thermodynamically inhibits the precipitation of drug molecules by retarding nucleation and crystal growth in the aqueous medium. Self-emulsification approach has been successful in the delivery of anti-cancer agents, anti-viral drugs, anti-bacterial, immunosuppressant, and natural products such as antioxidants as well as alkaloids. At present, more than four SEDDS drug products are available in the market. SEDDS have tremendous capabilities which are yet to be explored which would be beneficial in oral lipid delivery.


self-emulsification SEDDS SNEDDS SMEDDS lipid delivery 



  1. 1.
    Mahmooda A, Bernkop-Schnurch AM. SEDDS: a game changing approach for the oral administration of hydrophilic macromolecular drugs. Adv Drug Del Rev. 2018.
  2. 2.
    Viswanathan P, Muralidaran Y, Ragavan G. Challenges in oral drug delivery: a nano-based strategy to overcome nanostructures for oral medicine in EA Grumezescu. Nanostruct Oral Med. 2017:173–20.Google Scholar
  3. 3.
    Gupta H, Bhandari D, Sharma. A recent trends in oral drug delivery: a review. Recent Pat Drug Deliv Formul. 2009;3:162–73.CrossRefGoogle Scholar
  4. 4.
    Verma P, Thakur AS, Deshmukh K, Jha AK, Verma S. Routes of drug administration. Int J Pharm Res. 2010;1:54–9.Google Scholar
  5. 5.
    Feeney OM, Crum MF, McEvoy CL, Trevaskis NL, Pouton CW, Charman WN, et al. 50 years of oral lipid-based formulations: provenance, progress and future perspectives. Adv Drug Del Rev. 2016;101:167–94.CrossRefGoogle Scholar
  6. 6.
    Kalepun S, Manthina M, Padavala V. Oral lipid-based drug delivery systems: an overview. Acta Pharm Sin B. 2013;3:361–72.CrossRefGoogle Scholar
  7. 7.
    Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58:173–82.CrossRefGoogle Scholar
  8. 8.
    Karan M, Rajashree CM, Arti RT. Challenges in oral delivery: role of P-gp efflux pump. Curr Drug Ther. 2014;9:47–55.CrossRefGoogle Scholar
  9. 9.
    Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Del Rev. 1997;25:47–58.CrossRefGoogle Scholar
  10. 10.
    Kosnik AC, Szekalska M, Amelian A, Szymanska E. Development and evaluation of liquid and solid self-emulsifying drug delivery system for atorvastatin. Molecules. 2015;20:21010–22.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Craig DQM, Lievens HSR, Pitt KG, Storey DE. An investigation into the physicochemical properties of self-emulsifying systems using low frequency dielectric spectroscopy, surface tension measurement and particle size analysis. Int J Pharm. 1993;96:147–55.CrossRefGoogle Scholar
  13. 13.
    Mahapatra AK, Murthy PN. Self-emulsifying drug delivery systems (SEDDS): an update from formulation development to therapeutic strategies. Int J Pharm Tech Res. 2014;6:545–68.Google Scholar
  14. 14.
    Sebastain G, Rajasree PH, George J, Gowda DV. Self-micron emulsifying drug delivery systems (SMEEDS) as a potential drug delivery system-novel applications and future perspectives: a review. Int J Pharm. 2016;6:105–10.Google Scholar
  15. 15.
    Patel SN, Patel DN, Patel TD, Prajapati TH, Parikh BN. Self-emulsifying drug delivery system. J Glob Pharm Tech. 2010;2:29–37.Google Scholar
  16. 16.
    Xu X, Cao M, Ren L, Qian Y, Chen G. Preparation and optimization of rivaroxaban by self-nanoemulsifying drug delivery system (SNEDDS) for enhanced oral bioavailability and no food effect. AAPS PharmSciTech. 2018;19:1847–59.CrossRefGoogle Scholar
  17. 17.
    Khedekar K, Mittal S. Self-emulsifying drug delivery system: a review. Int J Pharm Sci Res. 2013;4:4494–507.Google Scholar
  18. 18.
    Fotouh KA, Allam AA, El-Badry M, El-Sayed AM. Self-emulsifying drug-delivery systems modulate P-glycoprotein activity: role of excipients and formulation aspects. Nanomedicine. 2018;13.
  19. 19.
    Lavra ZMM, Santana DPD, Re M.I. Solubility and dissolution performances of spray dried solid dispersion of efavirenz in soluplus. Drug Dev Ind Pharm 2017;43: 42–54.Google Scholar
  20. 20.
    Ikasari ED, Fudholi A, Martono S, Marchaban. Investigation of nifedipine solid dispersion with solvent PVP K-30. Int J Pharm Pharm Sci. 2015;7:389–92.Google Scholar
  21. 21.
    Hauss DJ, Fogal SE, Ficorilli JV, Price CA, Roy T, Jayaraj AA, et al. Lipid-based delivery systems for improving the bioavailability and lymphatic transport of poorly water-soluble LTB4 inhibitor. J Pharm Sci. 1998;87:164–9.CrossRefGoogle Scholar
  22. 22.
    Pillay V, Fassihi R. Unconventional dissolution methodologies. J Pharm Sci. 1999;88:843–51.CrossRefGoogle Scholar
  23. 23.
    Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci. 2000;2:S93–8.CrossRefGoogle Scholar
  24. 24.
    Kimura M, Shizuki M, Miyoshi K, Sakai T, Hidaka H, Takamura H, et al. Relationship between the molecular structures and emulsification properties of edible oils. Biosci Biotechnol Biochem. 1994;58:1258–61.CrossRefGoogle Scholar
  25. 25.
    Gershanik T, Benita S. Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone. Pharm Dev Technol. 1996;1:147–57.CrossRefGoogle Scholar
  26. 26.
    Reiss H. Entropy-induced dispersion of bulk liquids. J Colloid Interface Sci. 1975;53:61–70.CrossRefGoogle Scholar
  27. 27.
    Boltri L, Canal T, Esposito PA, Carli F. Lipid nanoparticles: evaluation of some critical formulation parameters. Proc Intern Symp Control Rel Bioact Mater. 1993;20:346–7.Google Scholar
  28. 28.
    Xu R. Progress in nanoparticles characterization: sizing and zeta potential measurement. Particuology. 2008;6:112–5.CrossRefGoogle Scholar
  29. 29.
    Pecora R. Dynamic light scattering measurement of nanometer particles in liquids. J Nanopart Res. 2009;2:123–31.CrossRefGoogle Scholar
  30. 30.
    Goddeeris C, Goderis B, van den Mooter G. Lyotropic, liquid crystalline nanostructures of aqueous dilutions of SMEDDS revealed by small-angle X-ray scattering: impact on solubility and drug release. Eur J Pharm Sci. 2010;40:110–7.CrossRefGoogle Scholar
  31. 31.
    Gradzielski M. Recent developments in the characterization of microemulsions. Curr Opin Cold Int Sci. 2008;13:263–9.CrossRefGoogle Scholar
  32. 32.
    Vogt FG. Solid-state characterization of amorphous dispersions. In: Newman A, editor. Amorph solid dispersions: Pharm; 2015. p. 117–78.Google Scholar
  33. 33.
    Elnaggar YSR, El-Massik MA, Abdallah OY. Self-nano-emulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm. 2009;380:133–41.CrossRefGoogle Scholar
  34. 34.
    Kataoka M, Sugano K, da Costa Mathews C. Application of dissolution/permeation system for evaluation of formulation effect on oral absorption of poorly water-soluble drugs in drug development. Pharm Res. 2012;29:1485–94.CrossRefGoogle Scholar
  35. 35.
    Simonelli AP, Mehta SC, Higuchi WI. Inhibition of sulfathiazole crystal growth by polyvinyl pyrrolidone. J Pharm Sci. 1970;59:633–8.CrossRefGoogle Scholar
  36. 36.
    Sekikawa H, Fujiwara J, Naganuma T, Nakano M, Arita T. Dissolution behaviors and gastrointestinal absorption of phenytoin in phenytoin-polyvinyl pyrrolidone coprecipitate. Chem Pharm Bull. 1978;26:3033–9.CrossRefGoogle Scholar
  37. 37.
    O’Driscoll KM, Corrigan OI. Chlorothiazidepolyvinyl pyrrolidone (PVP) interactions: influence on membrane permeation (everted rat intestine) and dissolution. Drug Dev and Ind Pharm. 1982;8:547–64.CrossRefGoogle Scholar
  38. 38.
    Megrab NA, Williams AC, Barry BW. Oestradiol permeation through human skin silastic membrane: effects of propylene glycol and supersaturation. J Control Release. 1995;36:277–94.CrossRefGoogle Scholar
  39. 39.
    Ma X, Taw J, Chiang C. Control of drug crystallization in transdermal matrix system. Int J Pharm. 1996;142:115–9.CrossRefGoogle Scholar
  40. 40.
    Schwarb FP, Imanidis G, Smith EW, Haigh JM, Surber C. Effect of concentration and degree of saturation of topical fluocinonide formulations availability on human skin. Pharm Res. 1997;16:909–15.CrossRefGoogle Scholar
  41. 41.
    Raghavan SL, Trividic A, Davis AF, Hadgraft J. Crystallization of hydrocortisone acetate: influence of polymers. Int J Pharm. 2001a;212:213–21.CrossRefGoogle Scholar
  42. 42.
    Raghavan RL, Kiepfer B, Davis AF, Kazarian SG, Hadgraft J. Membrane transport of hydrocortisone acetate from supersaturated solutions; the role of polymers. Int J Pharm. 2001b;221:95–105.CrossRefGoogle Scholar
  43. 43.
    Quan G, Niu B, Singh V, Zhou Y, Wu CY, Pan X, et al. Supersaturable solid self-micro emulsifying drug delivery system: precipitation inhibition and bioavailability enhancement. Int J Nanomed. 2017;12:8801–11.CrossRefGoogle Scholar
  44. 44.
    Gao P, Guyton ME, Huang T, Bauer J, Stefanski KJ, Lu Q. Enhanced oral bioavailability of a poorly water-soluble drug pnu-91325 by super saturatable formulations. Drug Dev Ind Pharm. 2004;30:221–9.CrossRefGoogle Scholar
  45. 45.
    Higuchi T. Physical chemical analysis of percutaneous absorption process. J Soc Cosmet Chem. 1960;11:85–97.Google Scholar
  46. 46.
    Halliwel B, Gutteridge JMC. The definition and measurement of antioxidants in biological systems. Free Radic Biol Med. 1995;18:125–6.CrossRefGoogle Scholar
  47. 47.
    Li F, Hu R, Wang B, Gui Y, Cheng G, Gao S, et al. Self-microemulsifying drug delivery system for improving the bioavailability of huperzine A by lymphatic uptake. Acta Pharm Sin B. 2017;7(3):353–60.CrossRefGoogle Scholar
  48. 48.
    Charman WN, Stella VJ. Estimating the maximal potentials for intestinal lymphatic transport of lipophilic drug molecules. Int J Pharm. 1986;34:175–8.CrossRefGoogle Scholar
  49. 49.
    Jain S, Jain AK, Pohekar M, Kaushik T. Novel self-emulsifying formulation of quercetin for improved in vivo antioxidant potential: implications on drug induced cardiotoxicity and nephrotoxicity. Free Radic Biol Med. 2013;65:117–30.CrossRefGoogle Scholar
  50. 50.
    Mamadou GC, Charrueau JD, Nzouzi NL, Eto B, Ponchel G. Increased intestinal permeation and modulation of pre-systemic metabolism of resveratrol formulated into self-emulsifying drug delivery systems. Int J Pharm. 2017;521:150–5.CrossRefGoogle Scholar
  51. 51.
    Andey T, Patel A, Marepally S, Chougule M, Spencer SD, Rishi AK, et al. Formulation, pharmacokinetic, and efficacy studies of mannosylated self-emulsifying solid dispersions of noscapine. PLoS One. 2016;11:e0146804.CrossRefGoogle Scholar
  52. 52.
    Seo YG, Kima DH, Ramasamy T, Kim JH, Marasini N, Oh YK, et al. Development of docetaxel-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced chemotherapeutic effect. Int J Pharm. 2013;452:412–20.CrossRefGoogle Scholar
  53. 53.
    Wang YJ, Sun J, Zhang T, Liu H, He F, He Z. Enhanced oral bioavailability of tacrolimus in rats by self-micro emulsifying drug delivery systems. Drug Dev and Ind Pharm. 2011;37:1225–30.CrossRefGoogle Scholar
  54. 54.
    Patela AR, Doddapanenia R, Andeya T, Wilson H, Safeb S, Singh M. Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity. J Control Release. 2015;10:18–26.CrossRefGoogle Scholar
  55. 55.
    Wang Y, Yu N, Guo R, Yang M, Shan L, Huang W, et al. Enhancing in vivo bioavailability in beagle dogs of GLM-7 as a novel anti-leukemia drug through a self-emulsifying drug delivery system for oral delivery. Curr Drug Deliv. 2016;13:131–42.CrossRefGoogle Scholar
  56. 56.
    Gurav NP, Dandagi MP, Gadad AP, Masthiholimath VS. Solubility enhancement of satranidazole using self-emulsified drug delivery systems. Ind J Pharm Educ Res. 2015;50:3. Google Scholar
  57. 57.
    Wasan EK, Bartlett K, Gershkovich P, Sivak O, Banno B, Wong Z, et al. Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans. Int J Pharm. 2009;372:76–84.CrossRefGoogle Scholar
  58. 58.
    Cohen SJW, Schuurman R, Burger DM, Koopmans PP, Sprenger HG, Juttman JR, et al. Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). JAIDS. 1999;13:53–8.Google Scholar
  59. 59.
    Buss N, Snell P, Bock J, Hsu A, Jorga K. Saquinavir and ritonavir pharmacokinetics following combined ritonavir and saquinavir (soft gelatin capsules) administration. Br J Clin Pharmacol. 2001;52:255–64.CrossRefGoogle Scholar
  60. 60.
    Jing B, Wang Z, Yang R, Zheng X, Zhao X, Tang S, and He Z. Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets. Drug Dev Ind Pharm. 2016;42:506–12.Google Scholar
  61. 61.
    Bakhle SS, Avari JG. Development and characterization of solid self-emulsifying drug delivery system of cilnidipine. Chem Pharm Bull. 2015;63:408–17.CrossRefGoogle Scholar
  62. 62.
    Boxin OU, Dejian H, Maureen AF, Elizabeth KD. Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem. 2002;5:223–8.Google Scholar
  63. 63.
    Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine. 2010;5:1595–616.CrossRefGoogle Scholar
  64. 64.
    Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Disov. 2006;5:493–506.CrossRefGoogle Scholar
  65. 65.
    Chen Y, Zhang H, Yang J, Sun H. Improved antioxidant capacity of optimization of a self-microemulsifying drug delivery system for resveratrol. Molecules. 2015;20:21167–77.CrossRefGoogle Scholar
  66. 66.
    Li W, Shao Y, Hu L. BM6, a new semi-synthetic vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles. Cancer Biol Ther. 2007;6:787–94.CrossRefGoogle Scholar
  67. 67.
    Liu Z, Liu D, Wang L, Zhang J, Zhang N. Docetaxel-loaded pluronic P123 polymeric micelles: in vitro and in vivo evaluation. Int J Mol Sci. 2011;12:1684–96.CrossRefGoogle Scholar
  68. 68.
    Sun S. Acrylamide derivative and use thereof in manufacture of medicament. 2010; Patent, US2012/0116075A1.Google Scholar
  69. 69.
    Sun S. Acrylamide derivative and use thereof in manufacture of medicament. 2010; Patent, CN102421754B.Google Scholar
  70. 70.
    Yeni P. Tipranavir: a protease inhibitor from a new class with distinct antiviral activity. JAIDS. 2003;34:S91–4.PubMedGoogle Scholar
  71. 71.
    Meng J, Li S, Yao Q, Zhang L, Weng Y, Cai C, et al. In vitro/in vivo evaluation of felodipine micropowders prepared by the wet-milling process combined with different solidification methods. Drug Dev Ind Pharm. 2014;40:929–36.CrossRefGoogle Scholar
  72. 72.
    Karavas E, Ktistis G, Xenakis A, Georgarakis E. Miscibility behavior and formation mechanism of stabilized felodipine-polyvinyl pyrrolidone amorphous solid dispersions. Drug Dev Ind Pharm. 2005;31:473–89.CrossRefGoogle Scholar
  73. 73.
    Tarr BD, Yalkowsky SH. Enhanced intestinal absorption of cyclosporin in rats through the reduction of emulsion droplet size. Pharm Res. 1989;6:40–3.CrossRefGoogle Scholar
  74. 74.
    Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12:1561–72.CrossRefGoogle Scholar
  75. 75.
    Kauss T, Gaubert A, Tabaran L, Tonelli G, Phoeung T, Langlois MH, et al. Development of rectal self-emulsifying suspension of a moisture-labile water-soluble drug. Int J Pharm. 2018;536:283–91.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, School of Chemical Sciences and PharmacyCentral University of RajasthanAjmerIndia
  2. 2.School of Pharmacy and Technology ManagementNMIMSShirpurIndia

Personalised recommendations