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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

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Review Article

Self-emulsifying Drug Delivery System Improve Oral Bioavailability: Role of Excipients and Physico-chemical Characterization

Author(s): Yujin Zhu, Jing Ye and Quan Zhang*

Volume 8, Issue 4, 2020

Page: [290 - 301] Pages: 12

DOI: 10.2174/2211738508666200811104240

Price: $65

Abstract

Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion (micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore, SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous system, consequently being suitable for large-scale production and more stable than conventional emulsion. However, the role of formulation aspects in the biological property of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug bioavailability, we need to fully understand the various factors that affect the in vivo behavior of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS on the oral drug bioavailability enhancement. This review would provide an approach to develop a rational SEDDS to improving oral drug bioavailability.

Lay Summary: Self-emulsifying drug-delivery system (SEDDS) has been proven to be promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review highlighted the influence of excipients and physicochemical property of SEDDS on the formation of emulsion and the oral absorption of drugs in the body.

Keywords: Chylomicron, excipient, lymphatic transport, oral bioavailability, physicochemical property, self-emulsifying drug delivery systems (SEDDS).

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[1]
Mandić J, Zvonar Pobirk A, Vrečer F, Gašperlin M. Overview of solidification techniques for self emulsifying drug delivery systems from industrial perspective. Int J Pharm 2017; 533(2): 335-45.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.036] [PMID: 28528850]
[2]
Dokania S, Joshi AK. Self-microemulsifying drug delivery system (SMEDDS)--challenges and road ahead. Drug Deliv 2015; 22(6): 675-90.
[http://dx.doi.org/10.3109/10717544.2014.896058] [PMID: 24670091]
[3]
Čerpnjak K, Zvonar A, Gašperlin M, Vrečer F. Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs 2013; 63(4): 427.
[http://dx.doi.org/10.2478/acph-2013-0040]
[4]
Chatterjee B, Hamed AS, Ahmed MDA, Mandal UK, Sengupta P. Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. Drug Deliv 2016; 23(9): 3639-52.
[http://dx.doi.org/10.1080/10717544.2016.1214990] [PMID: 27685505]
[5]
Singh B, Beg S, Khurana RK, Sandhu PS, Kaur R, Katare OP. Recent advances in self-emulsifying drug delivery systems (SEDDS). Crit Rev Ther Drug Carrier Syst 2014; 31(2): 121-85.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2014008502] [PMID: 24940626]
[6]
Palamakula A, Khan MA. Evaluation of cytotoxicity of oils used in coenzyme Q10 Self-emulsifying Drug Delivery Systems (SEDDS). Int J Pharm 2004; 273(1-2): 63-73.
[http://dx.doi.org/10.1016/j.ijpharm.2003.12.010] [PMID: 15010131]
[7]
Ali H, Nazzal M, Zaghloul AA, Nazzal S. Comparison between lipolysis and compendial dissolution as alternative techniques for the in vitro characterization of α-tocopherol self-emulsified drug delivery systems (SEDDS). Int J Pharm 2008; 352(1-2): 104-14.
[http://dx.doi.org/10.1016/j.ijpharm.2007.10.023] [PMID: 18065173]
[8]
Siepmann J, Faham A, Clas SD, et al. Lipids and polymers in pharmaceutical technology: lifelong companions. Int J Pharm 2019; 558: 128-42.
[http://dx.doi.org/10.1016/j.ijpharm.2018.12.080] [PMID: 30639218]
[9]
Pereira de Sousa I, Bernkop-Schnürch A. Pre-systemic metabolism of orally administered drugs and strategies to overcome it. J Control Release 2014; 192: 301-9.
[http://dx.doi.org/10.1016/j.jconrel.2014.08.004] [PMID: 25128718]
[10]
Hsu CY, Wang PW, Alalaiwe A, Lin ZC, Fang JY. Use of lipid nanocarriers to improve oral delivery of vitamins. Nutrients 2019; 11(1): 68.
[http://dx.doi.org/10.3390/nu11010068] [PMID: 30609658]
[11]
Chen ML. Lipid excipients and delivery systems for pharmaceutical development: a regulatory perspective. Adv Drug Deliv Rev 2008; 60(6): 768-77.
[http://dx.doi.org/10.1016/j.addr.2007.09.010] [PMID: 18077051]
[12]
Hauss DJ, Fogal SE, Ficorilli JV, et al. Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. J Pharm Sci 1998; 87(2): 164-9.
[http://dx.doi.org/10.1021/js970300n] [PMID: 9519148]
[13]
Shan W, Zhu X, Liu M, et al. Overcoming the diffusion barrier of mucus and absorption barrier of epithelium by self-assembled nanoparticles for oral delivery of insulin. ACS Nano 2015; 9(3): 2345-56.
[http://dx.doi.org/10.1021/acsnano.5b00028] [PMID: 25658958]
[14]
Singh B, Bandopadhyay S, Kapil R, Singh R, Katare O. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit Rev Ther Drug Carrier Syst 2009; 26(5): 427-521.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i5.10] [PMID: 20136631]
[15]
Liao TH, Hamosh P, Hamosh M. Fat digestion by lingual lipase: mechanism of lipolysis in the stomach and upper small intestine. Pediatr Res 1984; 18(5): 402-9.
[http://dx.doi.org/10.1203/00006450-198405000-00002] [PMID: 6728567]
[16]
Xiao C, Stahel P, Lewis GF. Regulation of chylomicron secretion: focus on post-assembly mechanisms. Cell Mol Gastroenterol Hepatol 2019; 7(3): 487-501.
[http://dx.doi.org/10.1016/j.jcmgh.2018.10.015] [PMID: 30819663]
[17]
Takahara E, Yuasa H, Nishida M, et al. Immunohistochemical and histoplanimetrical study on the endothelial receptor involved in transportation of minute chylomicrons into subepithelial portal blood in intestinal villi of the rat jejunum. J Vet Med Sci 2015; 77(4): 387-93.
[http://dx.doi.org/10.1292/jvms.14-0432] [PMID: 25502363]
[18]
Tian C, Guo J, Wang G, et al. Efficient intestinal digestion and on site tumor-bioactivation are the two important determinants for chylomicron-mediated lymph-targeting triglyceride-mimetic docetaxel oral prodrugs. Adv Sci (Weinh) 2019; 6(24) 1901810.
[http://dx.doi.org/10.1002/advs.201901810] [PMID: 31871861]
[19]
Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces 2012; 100: 50-61.
[http://dx.doi.org/10.1016/j.colsurfb.2012.05.019] [PMID: 22766282]
[20]
AboulFotouh K. Allam AA, El-Badry M, El-Sayed AM. Self-emulsifying drug-delivery systems modulate P-glycoprotein activity: role of excipients and formulation aspects. Nanomedicine (Lond) 2018; 13(14): 1813-34.
[http://dx.doi.org/10.2217/nnm-2017-0354] [PMID: 30074420]
[21]
Land LM, Li P, Bummer PM. The influence of water content of triglyceride oils on the solubility of steroids. Pharm Res 2005; 22(5): 784-8.
[http://dx.doi.org/10.1007/s11095-005-2595-6] [PMID: 15906174]
[22]
Rahman MA, Hussain A, Hussain MS, Mirza MA, Iqbal Z. Role of excipients in successful development of self-emulsifying/microemulsifying drug delivery system (SEDDS/SMEDDS). Drug Dev Ind Pharm 2013; 39(1): 1-19.
[http://dx.doi.org/10.3109/03639045.2012.660949] [PMID: 22372916]
[23]
Dahan A, Hoffman A. Use of a dynamic in vitro lipolysis model to rationalize oral formulation development for poor water soluble drugs: correlation with in vivo data and the relationship to intra-enterocyte processes in rats. Pharm Res 2006; 23(9): 2165-74.
[http://dx.doi.org/10.1007/s11095-006-9054-x] [PMID: 16902814]
[24]
Fatouros DG, Nielsen FS, Douroumis D, Hadjileontiadis LJ, Mullertz A. In vitro-in vivo correlations of self-emulsifying drug delivery systems combining the dynamic lipolysis model and neuro-fuzzy networks. Eur J Pharm Biopharm 2008; 69(3): 887-98.
[http://dx.doi.org/10.1016/j.ejpb.2008.01.022] [PMID: 18367386]
[25]
Jannin V, Musakhanian J, Marchaud D. Approaches for the development of solid and semi-solid lipid-based formulations. Adv Drug Deliv Rev 2008; 60(6): 734-46.
[http://dx.doi.org/10.1016/j.addr.2007.09.006] [PMID: 18045728]
[26]
Alayoubi A, Aqueel MS, Cruz CN, Ashraf M, Zidan AS. Application of in vitro lipolysis for the development of oral self-emulsified delivery system of nimodipine. Int J Pharm 2018; 553(1-2): 441-53.
[http://dx.doi.org/10.1016/j.ijpharm.2018.10.066] [PMID: 30385374]
[27]
Kohli K, Chopra S, Dhar D, Arora S, Khar RK. Self-emulsifying drug delivery systems: an approach to enhance oral bioavailability. Drug Discov Today 2010; 15(21-22): 958-65.
[http://dx.doi.org/10.1016/j.drudis.2010.08.007] [PMID: 20727418]
[28]
Park H, Ha ES, Kim MS. Current status of supersaturable self-emulsifying drug delivery systems. Pharmaceutics 2020; 12(4) E365.
[http://dx.doi.org/10.3390/pharmaceutics12040365] [PMID: 32316199]
[29]
Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006; 29(3-4): 278-87.
[http://dx.doi.org/10.1016/j.ejps.2006.04.016] [PMID: 16815001]
[30]
Nanjwade BK, Patel DJ, Udhani RA, Manvi FV. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci Pharm 2011; 79(4): 705-27.
[http://dx.doi.org/10.3797/scipharm.1105-09] [PMID: 22145101]
[31]
Erlanson-Albertsson C. Pancreatic colipase. Structural and physiological aspects. Biochim Biophys Acta 1992; 1125(1): 1-7.
[http://dx.doi.org/10.1016/0005-2760(92)90147-N] [PMID: 1567900]
[32]
Devraj R, Williams HD, Warren DB, Mullertz A, Porter CJ, Pouton CW. In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products. Int J Pharm 2013; 441(1-2): 323-33.
[http://dx.doi.org/10.1016/j.ijpharm.2012.11.024] [PMID: 23178598]
[33]
Patton JS, Carey MC. Inhibition of human pancreatic lipase-colipase activity by mixed bile salt phospholipid micelles. Am J Physiol 1981; 241(4): G328-36.
[PMID: 7315970]
[34]
Vithani K, Jannin V, Pouton CW, Boyd BJ. Colloidal aspects of dispersion and digestion of self-dispersing lipid-based formulations for poorly water-soluble drugs. Adv Drug Deliv Rev 2019; 142: 16-34.
[http://dx.doi.org/10.1016/j.addr.2019.01.008] [PMID: 30677448]
[35]
Moscow JA, Fairchild CR, Madden MJ, et al. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res 1989; 49(6): 1422-8.
[PMID: 2466554]
[36]
Sugawara I, Hamada H, Nakahama M, Okamoto S, Tsuruo T, Mori S. Further characterization of the human adrenal-derived P-glycoprotein recognized by monoclonal antibody MRK 16 reacting with only human P-glycoprotein. Jpn J Cancer Res 1989; 80(12): 1199-205.
[http://dx.doi.org/10.1111/j.1349-7006.1989.tb01655.x] [PMID: 2576426]
[37]
Bansal T, Akhtar N, Jaggi M, Khar RK, Talegaonkar S. Novel formulation approaches for optimising delivery of anticancer drugs based on P-glycoprotein modulation. Drug Discov Today 2009; 14(21-22): 1067-74.
[http://dx.doi.org/10.1016/j.drudis.2009.07.010] [PMID: 19647803]
[38]
Srivalli KMR, Lakshmi PK. Overview of P-glycoprotein inhibitors: a rational outlook. Braz J Pharm Sci 2012; 48(3): 353-67.
[http://dx.doi.org/10.1590/S1984-82502012000300002]
[39]
Mittal K, Mashru R, Thakkar A. Challenges in oral delivery: role of P-gp efflux pump. Curr Drug Ther 2014; 9(1): 47-55.
[http://dx.doi.org/10.2174/1574885509666140805003456]
[40]
Kim S-W, Kwon HY, Chi D-W, et al. Reversal of P-glycoprotein-mediated multidrug resistance by ginsenoside Rg(3). Biochem Pharmacol 2003; 65(1): 75-82.
[http://dx.doi.org/10.1016/S0006-2952(02)01446-6] [PMID: 12473381]
[41]
Wan CK, Zhu GY, Shen XL, Chattopadhyay A, Dey S, Fong WF. Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated multidrug resistance in HepG2-DR cells. Biochem Pharmacol 2006; 72(7): 824-37.
[http://dx.doi.org/10.1016/j.bcp.2006.06.036] [PMID: 16889754]
[42]
Elgart A, Cherniakov I, Aldouby Y, Domb AJ, Hoffman A. Improved oral bioavailability of BCS class 2 compounds by self nano-emulsifying drug delivery systems (SNEDDS): the underlying mechanisms for amiodarone and talinolol. Pharm Res 2013; 30(12): 3029-44.
[http://dx.doi.org/10.1007/s11095-013-1063-y] [PMID: 23686373]
[43]
Chavanpatil MD, Patil Y, Panyam J. Susceptibility of nanoparticle-encapsulated paclitaxel to P-glycoprotein-mediated drug efflux. Int J Pharm 2006; 320(1-2): 150-6.
[http://dx.doi.org/10.1016/j.ijpharm.2006.03.045] [PMID: 16713148]
[44]
Sun M, Zhai X, Xue K, et al. Intestinal absorption and intestinal lymphatic transport of sirolimus from self-microemulsifying drug delivery systems assessed using the single-pass intestinal perfusion (SPIP) technique and a chylomicron flow blocking approach: linear correlation with oral bioavailabilities in rats. Eur J Pharm Sci 2011; 43(3): 132-40.
[45]
Nekkanti V, Rueda J, Wang Z, Betageri GV. Comparative evaluation of proliposomes and self micro emulsifying drug delivery system for improved oral bioavailability of nisoldipine. Int J Pharm 2016; 505(1-2): 79-88.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.065] [PMID: 27041124]
[46]
Chitneni M, Peh KK, Darwis D, Abdulkarim M, Abdullah GZ, Qureshi MJ. Intestinal permeability studies of sulpiride incorporated into self-microemulsifying drug delivery system (SMEDDS). Pak J Pharm Sci 2011; 24(2): 113-21.
[PMID: 21454158]
[47]
Yang S, Gursoy RN, Lambert G, Benita S. Enhanced oral absorption of paclitaxel in a novel self-microemulsifying drug delivery system with or without concomitant use of P-glycoprotein inhibitors. Pharm Res 2004; 21(2): 261-70.
[http://dx.doi.org/10.1023/B:PHAM.0000016238.44452.f1] [PMID: 15032307]
[48]
Liu M, Zhang J, Shan W, Huang Y. Developments of mucus penetrating nanoparticles. Asian J Pharm Sci 2015; 10(4): 275-82.
[http://dx.doi.org/10.1016/j.ajps.2014.12.007]
[49]
Netsomboon K, Bernkop-Schnürch A. Mucoadhesive vs. mucopenetrating particulate drug delivery. Eur J Pharm Biopharm 2016; 98: 76-89.
[http://dx.doi.org/10.1016/j.ejpb.2015.11.003] [PMID: 26598207]
[50]
Bruno BJ, Miller GD, Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013; 4(11): 1443-67.
[http://dx.doi.org/10.4155/tde.13.104] [PMID: 24228993]
[51]
Abdulkarim M, Sharma PK, Gumbleton M. Self-emulsifying drug delivery system: mucus permeation and innovative quantification technologies. Adv Drug Deliv Rev 2019; 142: 62-74.
[http://dx.doi.org/10.1016/j.addr.2019.04.001] [PMID: 30974131]
[52]
Suchaoin W, Pereira de Sousa I, Netsomboon K, Lam HT, Laffleur F, Bernkop-Schnürch A. Development and in vitro evaluation of zeta potential changing self-emulsifying drug delivery systems for enhanced mucus permeation. Int J Pharm 2016; 510(1): 255-62.
[http://dx.doi.org/10.1016/j.ijpharm.2016.06.045] [PMID: 27329673]
[53]
Hintzen F, Perera G, Hauptstein S, Müller C, Laffleur F, Bernkop-Schnürch A. In vivo evaluation of an oral self-microemulsifying drug delivery system (SMEDDS) for leuprorelin. Int J Pharm 2014; 472(1-2): 20-6.
[http://dx.doi.org/10.1016/j.ijpharm.2014.05.047] [PMID: 24879935]
[54]
Xu S, Dai WG. Drug precipitation inhibitors in supersaturable formulations. Int J Pharm 2013; 453(1): 36-43.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.013] [PMID: 23680727]
[55]
Gao P, Rush BD, Pfund WP, et al. Development of a supersaturable SEDDS (S-SEDDS) formulation of paclitaxel with improved oral bioavailability. J Pharm Sci 2003; 92(12): 2386-98.
[http://dx.doi.org/10.1002/jps.10511] [PMID: 14603484]
[56]
Lee DH, Yeom DW, Song YS, et al. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system (S-SEDDS). Int J Pharm 2015; 478(1): 341-7.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.060] [PMID: 25437113]
[57]
Tarr BD, Yalkowsky SH. Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size. Pharm Res 1989; 6(1): 40-3.
[http://dx.doi.org/10.1023/A:1015843517762] [PMID: 2717516]
[58]
Bekerman T, Golenser J, Domb A. Cyclosporin nanoparticulate lipospheres for oral administration. J Pharm Sci 2004; 93(5): 1264-70.
[http://dx.doi.org/10.1002/jps.20057] [PMID: 15067702]
[59]
Sek L, Boyd BJ, Charman WN, Porter CJ. Examination of the impact of a range of Pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone. J Pharm Pharmacol 2006; 58(6): 809-20.
[http://dx.doi.org/10.1211/jpp.58.6.0011] [PMID: 16734982]
[60]
Lai SK, O’Hanlon DE, Harrold S, et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci USA 2007; 104(5): 1482-7.
[http://dx.doi.org/10.1073/pnas.0608611104] [PMID: 17244708]
[61]
Brown AL Jr. Microvilli of the human jejunal epithelial cell. J Cell Biol 1962; 12(3): 623-7.
[http://dx.doi.org/10.1083/jcb.12.3.623] [PMID: 13873575]
[62]
Pereira de Sousa I, Steiner C, Schmutzler M, et al. Mucus permeating carriers: formulation and characterization of highly densely charged nanoparticles. Eur J Pharm Biopharm 2015; 97(Pt A): 273-9.
[http://dx.doi.org/10.1016/j.ejpb.2014.12.02] [PMID: 25576256]
[63]
Wolf JD, Kurpiers M, Götz RX, et al. Phosphorylated PEG-emulsifier: Powerful tool for development of zeta potential changing self-emulsifying drug delivery systems (SEDDS). Eur J Pharm Biopharm 2020; 150: 77-86.
[http://dx.doi.org/10.1016/j.ejpb.2020.03.004] [PMID: 32151729]
[64]
Nazir I, Fürst A, Lupo N, Hupfauf A, Gust R, Bernkop-Schnürch A. Zeta potential changing self-emulsifying drug delivery systems: a promising strategy to sequentially overcome mucus and epithelial barrier. Eur J Pharm Biopharm 2019; 144: 40-9.
[http://dx.doi.org/10.1016/j.ejpb.2019.09.007] [PMID: 31505225]

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