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

  • Review Article
  • Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
  • Published:
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Abstract

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.

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References

  1. Mahmooda A, Bernkop-Schnurch AM. SEDDS: a game changing approach for the oral administration of hydrophilic macromolecular drugs. Adv Drug Del Rev. 2018. https://doi.org/10.1016/j.addr.2018.07.001.

  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.

  3. Gupta H, Bhandari D, Sharma. A recent trends in oral drug delivery: a review. Recent Pat Drug Deliv Formul. 2009;3:162–73.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  6. Kalepun S, Manthina M, Padavala V. Oral lipid-based drug delivery systems: an overview. Acta Pharm Sin B. 2013;3:361–72.

    Article  Google Scholar 

  7. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58:173–82.

    Article  PubMed  CAS  Google Scholar 

  8. Karan M, Rajashree CM, Arti RT. Challenges in oral delivery: role of P-gp efflux pump. Curr Drug Ther. 2014;9:47–55.

    Article  CAS  Google Scholar 

  9. Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Del Rev. 1997;25:47–58.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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. Patel SN, Patel DN, Patel TD, Prajapati TH, Parikh BN. Self-emulsifying drug delivery system. J Glob Pharm Tech. 2010;2:29–37.

    CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  17. Khedekar K, Mittal S. Self-emulsifying drug delivery system: a review. Int J Pharm Sci Res. 2013;4:4494–507.

    CAS  Google Scholar 

  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. https://doi.org/10.2217/nnm-2017-0354.

  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.

  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.

    CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  22. Pillay V, Fassihi R. Unconventional dissolution methodologies. J Pharm Sci. 1999;88:843–51.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  25. Gershanik T, Benita S. Positively charged self-emulsifying oil formulation for improving oral bioavailability of progesterone. Pharm Dev Technol. 1996;1:147–57.

    Article  CAS  PubMed  Google Scholar 

  26. Reiss H. Entropy-induced dispersion of bulk liquids. J Colloid Interface Sci. 1975;53:61–70.

    Article  Google Scholar 

  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. Xu R. Progress in nanoparticles characterization: sizing and zeta potential measurement. Particuology. 2008;6:112–5.

    Article  CAS  Google Scholar 

  29. Pecora R. Dynamic light scattering measurement of nanometer particles in liquids. J Nanopart Res. 2009;2:123–31.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  31. Gradzielski M. Recent developments in the characterization of microemulsions. Curr Opin Cold Int Sci. 2008;13:263–9.

    Article  CAS  Google Scholar 

  32. Vogt FG. Solid-state characterization of amorphous dispersions. In: Newman A, editor. Amorph solid dispersions: Pharm; 2015. p. 117–78.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  35. Simonelli AP, Mehta SC, Higuchi WI. Inhibition of sulfathiazole crystal growth by polyvinyl pyrrolidone. J Pharm Sci. 1970;59:633–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  39. Ma X, Taw J, Chiang C. Control of drug crystallization in transdermal matrix system. Int J Pharm. 1996;142:115–9.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  41. Raghavan SL, Trividic A, Davis AF, Hadgraft J. Crystallization of hydrocortisone acetate: influence of polymers. Int J Pharm. 2001a;212:213–21.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  45. Higuchi T. Physical chemical analysis of percutaneous absorption process. J Soc Cosmet Chem. 1960;11:85–97.

    Google Scholar 

  46. Halliwel B, Gutteridge JMC. The definition and measurement of antioxidants in biological systems. Free Radic Biol Med. 1995;18:125–6.

    Article  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Charman WN, Stella VJ. Estimating the maximal potentials for intestinal lymphatic transport of lipophilic drug molecules. Int J Pharm. 1986;34:175–8.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

  61. Bakhle SS, Avari JG. Development and characterization of solid self-emulsifying drug delivery system of cilnidipine. Chem Pharm Bull. 2015;63:408–17.

    Article  CAS  Google Scholar 

  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. Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine. 2010;5:1595–616.

    Article  CAS  PubMed  Google Scholar 

  64. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Disov. 2006;5:493–506.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sun S. Acrylamide derivative and use thereof in manufacture of medicament. 2010; Patent, US2012/0116075A1.

  69. Sun S. Acrylamide derivative and use thereof in manufacture of medicament. 2010; Patent, CN102421754B.

  70. Yeni P. Tipranavir: a protease inhibitor from a new class with distinct antiviral activity. JAIDS. 2003;34:S91–4.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  74. Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995;12:1561–72.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India

    Sarita Rani, Rafquat Rana, Vipin Kumar & Umesh Gupta

  2. School of Pharmacy and Technology Management, NMIMS, Mukesh Patel Technology Park, Babulde, Near Bank of Tapi River, Mumbai Agra Highway, Shirpur, Maharashtra, 425405, India

    Gaurav K. Saraogi

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  1. Sarita Rani
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  2. Rafquat Rana
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Correspondence to Umesh Gupta.

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Rani, S., Rana, R., Saraogi, G.K. et al. Self-Emulsifying Oral Lipid Drug Delivery Systems: Advances and Challenges. AAPS PharmSciTech 20, 129 (2019). https://doi.org/10.1208/s12249-019-1335-x

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