A SYSTEMATIC REVIEW ON SELF-MICRO EMULSIFYING DRUG DELIVERY SYSTEMS: A POTENTIAL STRATEGY FOR DRUGS WITH POOR ORAL BIOAVAILABILITY
DOI:
https://doi.org/10.22159/ijap.2019v11i1.29978Keywords:
Absorption, Lipid-based excipients, Lymphatic uptake, Precipitation, SMEDDS, BioavailabilityAbstract
Currently a marked interest in developing lipid-based formulations to deliver lipophilic compounds. Self-emulsifying system has emerged as a dynamic strategy for delivering poorly water-soluble compounds. These systems can embrace a wide variety of oils, surfactants, and co-solvents. An immediate fine emulsion is obtained on exposure to water/gastro-intestinal fluids. The principal interest is to develop a robust formula for biopharmaceutical challenging drug molecules. Starting with a brief classification system, this review signifies diverse mechanisms concerning lipid-based excipients besides their role in influencing bioavailability, furthermore pertaining to their structured formulation aspects. Consecutive steps are vital in developing lipid-based systems for biopharmaceutical challenging actives. Such a crucial structured development is critical for achieving an optimum formula. Hence lipid excipients are initially scrutinized for their solubility and phase behavior, along with biological effects. Blends are screened by means of simple dilution test and are consequently studied with more advanced biopharmaceutical tests. After discerning of the principle formula, diverse technologies are offered to incorporate the fill-mass either in soft/hard gelatin capsules. There is also feasibility to formulated lipid-system as a solid dosage form. Although such solid technologies are desirable but such should not undermine the biopharmaceutical potential of lipid-formulations.
Downloads
References
Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery system; preparation techniques and dosage forms. Drug Discovery Today 2008;13:606-12.
Yao G, Li Y. Preparation, characterization and evaluation of self-micro emulsifying drug delivery systems (SMEDDSs) of ligusticum chuanxiong oil. Biomed Prev Nutr 2010;1:36-42.
Amri A, Clanche SL, Therond P, Bonnefont Rousselot D, Borderie D, Lai-Kuen R, et al. Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death. Eur J Pharm Biopharm 2013;86:418-26.
Pund S, Shete Y, Jagdale S. Multivariate analysis of physicochemical characteristics of lipid-based nano emulsifying cilostazol–quality by design. Colloids Surf B 2014;115:29-36.
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;29:278–87.
Hauss DJ. Oral lipid-based formulations. Adv Drug Delivery Rev 2007;59:667-76.
Nanjwade B, Patel DJ, Udhani R, Manvi F. Functions of lipids for enhancement of oral bioavailability of poorly water-soluble drugs. Sci Pharm 2011;879:705-27.
Mullertz A, Ogbonnaa A, Ren S, Rades T. New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs. J Pharm Pharmcol 2010;62:1622-36.
Singh AK, Chaurasiya A, Singh M, Upadhyay SC, Mukherjee R, Khar RK. Exemestane loaded self-micro emulsifying drug delivery system (SMEDDS) development and optimization. AAPS PharmSciTech 2008;9:628-34.
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;26:427-1.
Zidan AS, Sammour OA, Hammad MA, Megrab NA, Habib MJ, Khan MA. Quality by design: understanding the product variability of a self-nanoemulsified drug delivery system of cyclosporine A. J Pharm Sci 2007;96:2409-23.
Wang Z, Sun J, Wang Y, Liu X, Liu Y, Fu Q, et al. Solid self-emulsifying nitrendipine pellets: preparation and in vitro/in vivo evaluation. Int J Pharm 2010;38:1-6.
Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying, and self-micro emulsifying drug delivery systems. Eur J Pharm Sci 2000;11:S93-8.
Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother 2004;58:173-82.
Khan AW, Kotta S, Ansari SH, Sharma RK, Ali J. Potentials and challenges in self-nano emulsifying drug delivery systems. Expert Opin Drug Delivery 2012;9:1305-17.
Mahmoud EA, Bendas ER, Mohamed MI. Preparation and evaluation of self-nano emulsifying tablets of carvedilol. AAPS PharmSciTech 2009;10:183-92.
Gao P, Morozowich W. Development of super saturable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Delivery 2006;3:97-110.
Sonia Anand, Rishikesh Gupta, Prajapati SK. Self-micro emulsifying drug delivery system. Asian J Pharm Clin Res 2016;9:33-8.
Taha E, Ghorab D, Zaghloul AA. Bioavailability assessment of vitamin a self-nanoemulsified drug delivery systems in rats: a comparative study. Med Princ Pract 2007;16:355-9.
Sander C, Holm P. Porous magnesium aluminometasilicate tablets as a carrier of a cyclosporine self-emulsifying formulation. AAPS PharmSciTech 2009;10:1388-95.
Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discovery 2007;6:231-8.
Bowtle W. Materials, process, and manufacturing considerations for lipid-based hard-capsule formats. In: Hauss DJ. editor. Oral lipid-based formulations are enhancing the bioavailability of poorly water-soluble drugs. 1st ed. Vol. 170. New York: Informa Healthcare; 2010. p. 79-106.
Trevaskis NL, Charman WN, Porter CJH. Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update. Adv Drug Delivery Rev 2008;60:702-16.
Zhang P, Liu Y, Xu J. Preparation and evaluation of self-emulsifying drug delivery system of oridonin. Int J Pharm 2008;355:269-76.
Wasylaschuk WR, Harmon PA, Wagner G. Evaluation of hydroperoxides in common pharmaceutical excipients. J Pharm Sci 2007;96:106-16.
Driscoll CMO. Lipid-based formulations for intestinal lymphatic delivery. Eur J Pharm Sci 2002;15:405-15.
Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discovery 2007;6:231-48.
Charman WN, Porter CJ, Mithani S, Dressman JB. Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J Pharm Sci 1997;86:269-82.
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv Drug Delivery Rev 1997;25:103-28.
Pramod K, Peeyush K, Rajeev K, Nitish K, Rakesh K. An overview of lipid-based formulation for oral drug delivery. Drug Inv Today 2010;2:390-5.
Erlanson Albertsson C. Pancreatic colipase. Structural and physiological aspects. Biochim Biophys Acta 1992;1125:1-7.
Van den Bosch H, Postema NM, de Haas GH, van Deenen L. On the positional specificity of phospholipase a from the pancreas. Biochim Biophys Acta 1965;98:657-9.
Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Delivery Rev 2008;60:625–37.
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water-soluble drugs. Adv Drug Delivery Rev 1997;25:103-28.
Porter CJH, Charman WN. Uptake of drugs into intestinal lymhatics after oral administration. Adv Drug Delivery Rev 1997;25:71-89.
Pouton CW. SEDDS: assessment of the efficiency of the emulsion. Int J Pharm 1985;27:335-48.
Reiss H. Entropy induced dispersion of bulk liquids. J Colloid Interface Sci 1975;53:61-70.
Dabros T, Yeung A, Masliyah J, Czarnecki J. Emulsification through area contraction. J Colloid Interface Sci 1999;210:222-4.
Wakerly MG, Pouton CW, Meakin B, Morton F. Self emulsification of veg: oil-nonionic-surfactant mixtures. ACS Symp Ser 1986;311:242-55.
Wakerly MG, Pouton CW, Meakin BJ. Evaluation of the self-emulsifying performance of a non-ionic surfactant vegetable oil mixture. J Pharm Pharmacol 1987;39:6.
Gao P, Morozowich W. Improving the oral absorption of poorly soluble drug using SEDDS and S-SEDDS formulations. In: Qiu Y, Chen Y, Zhang GGZ. editors. Developing solid oral dosage forms theory and practice. 2nd ed. New York: Academic Press; 2009. p. 443-9.
Land LM, Li P, Bummer PM. The influence of water content of triglyceride oils on the solubility of steroids. Pharm Res 2005;22:784-8.
Hauss DJ. Oral lipid-based formulations. Adv Drug Delivery Rev 2007;59:667-76.
Azaz E, Donbrow M, Hamburger R. Incompatibility of non-ionic surfactants with oxidisable drugs. Pharm J 1973;211:15.
Carlert S, Palsson A, Hanisch G, Von Corswant C, Nilsson C, Lindfors L, et al. Predicting intestinal precipitation-a case example for a basic BCS class II drug. Pharm Res 2010;27:2119-30.
Rahman MA, Hussain A, Hussain MS, Mirza MA, Iqbal Z. Role of excipients in the successful development of self-emulsifying/micro-emulsifying drug delivery system (SEDDS/SMEDDS). Drug Dev Ind Pharm 2013;39:1-19.
Cuine JF, Mc Evoy CL, Charman WN, Pouton CW, Edwards GA, Benameur H, et al. Evaluation of the impact of surfactant digestion on the bioavailability of danazol after oral administration of lipidic self-emulsifying formulations to dogs. J Pharm Sci 2008;97:995-1012.
Pawar S, Kumar A. Issues in the formulation of drugs for oral use in children. Pediatr Drugs 2002;4:371-9.
Lopez Montilla JC, Herrera Morales PE, Pandey S, Shah DO. Spontaneous emulsification: mechanisms, physicochemical aspects, modeling, and applications. J Dispers Sci Technol 2002;23:219-68.
Basit AW, Podczeck F, Newton JM, Waddington WA, Ell PJ, Lacey LF. Influence of polyethylene glycol 400 on the gastrointestinal absorption of ranitidine. Pharm Res 2002;19:1368-74.
Schulze JDR, Waddington WA, Ell PJ, Parsons GE, Coffin MD, Basit AW. Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption. Pharm Res 2003;20:1984-8.
Amidon G, Lennernas H, Shah V, Crison J. A theoretical basisfor a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12:413-20.
Dressman J, Amidon G, Fleisher D. Absorption potential: estimation of the fraction absorbed for orally administered compounds. J Pharm Sci 1985;74:588-9.
Johnson K, Swindell A. Guidance in the setting of drug particle size specifications to minimize variability in absorption. Pharm Res 1996;13:1795-8.
Agoram B, Woltosz W, Bolger M. Predicting the impact of physiological and biochemical processes on oral drug bioavailability. Adv Drug Delivery Rev 2001;50:S41-67.
Willmann S, Schmitt W, Keldenich J, Lippert J, Dressman J. A physiological model for the estimation of the fraction dose absorbed in humans. J Med Chem 2004;47:4022-31.
Jamei M, Turner D, Yang J, Neuhoff S, Polak S, Rostami Hodjegan A, et al. Population-based mechanistic prediction of oral drug absorption. AAPS J 2009;11:225-37.
Kuentz M. Drug absorption modeling as a tool to define the strategy in clinical formulation development. AAPS J 2008;10:473-9.
Kuentz M, Nick S, Parrott N, Roethlisberger D. A strategy for preclinical formulation development using gastro plus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur J Pharm Sci 2006;27:91-9.
Wasswik CM, Holmen AG, Artursson P, Bergström CAS. Molecular characteristics for solid-state limited solubility. J Med Chem 2008;51:3035-9.
Jill B Shukla, Girish K Jani, Abdel Wahab Omri. Formulation and evaluation of oral self micro emulsifying drug delivery system of candesartan cilexetil. Int J Pharm Pharm Sci 2016;8:238-43.
GB Preethi, HN Shivakumar, M Ravi Kumar, N Sweta. Prototype self-emulsifying system of etravirine: design, formulation and in vitro evaluation. Int J Appl Pharm 2018;10:13-9.
Mette G, Anette M. Liquid self-micro emulsifying drug delivery systems. In: David JH. editor. Oral lipid-based formulations. Special ed. New Jersey: Informa healthcare; 2007. p. 107-27.
Padley FB, Gunstone FD, HarwoodJ L. Occurrence and characteristics of oils and fats. In: Gunstone FD, Harwood JL, Padley FB. editors. The lipid handbook. 2nd ed. London: Chapman and Hall; 1994. p. 47-224.
Hong JY, Kim JK, Song YK, Park JS, Kim CK. A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption. J Controlled Release 2006;110:332-8.
Patel AR, Vavia PR. Preparation and in vivo evaluation of SMEDDS (self-micro emulsifying drug delivery system) containing fenofibrate. AAPS J 2007;9:E344-52.
Swenson ES, Milisen WB, Curatolo W. Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility. Pharm Res 1994;11:1132-42.
Meinzer A, Mueller EA, Niese D, Choc G, Wong R, Vonderscher J, et al. Improved oral absorption of cyclosporine by using Neoral, a microemulsion formulation. In: Lieberman R, Mukherjee A. editors. Principles of Drug Development in Transplantation and Autoimmunity. Austin: RG Landes Company; 1996. p. 259-67.
Kuentz M, Wyttenbach N, Kuhlmann O. Application of a statistical method to the absorption of a new model drug from micellar and lipid formulations-evaluation of qualitative excipient effects. Pharm Dev Technol 2007;12:275-83.
Farah N, Laforet JP, Denis J. Self-micro emulsifying drug delivery systems (SMEDDS) for improving dissolution and availability of poorly soluble actives ingredients. BT Gattefosse 1992;87:41-7.
Constantinides PP, Welzel G, Ellens H, Smith PL, Sturgis SS, Yiv SH, et al. Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption evaluation. Pharm Res 1996;13:210-5.
Mohsin K, Long MA, Pouton CW. Design of lipid-based formulations for oral administration of poorly water-soluble drugs: precipitation of drug after dispersion of formulations in aqueous solution. J Pharm Sci 2009;98:3582-95.
Cui J, Yu B, Zhao Y, Zhu W, Li H, Lou H, et al. Enhancement of oral absorption of curcumin by self-micro emulsifying drug delivery systems. Int J Pharm 2009;371:148-55.
Troutman MD, Thakker DR. Novel experimental parameters to quantify the modulation of absorptive and secretory transporter of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res 2003;20:1210-24.
Collet A, Tanianis Hughes J, Hallifax D, Warhurst G. Predicting P-glycoprotein effects on absorption: correlation of transport in caco-2 with drug pharmacokinetics in wild-type and mdr1a (-/-) mice in vivo. Pharm Res 2004;21:819-26.
Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101:289-94.
Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993;268:6077-80.
Ueda K, Okamura N, Hirai M, Tanigawara Y, Saeki T, Kioka N, et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 1992;267:24248-52.
Kim WY, Benet LZ. P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res 2004;21:1284-93.
Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD, et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 2000;113:2011-21.
Burger H, Van Tol H, Boersma AW, Brok M, Wiemer EA, Stoter G, et al. Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 2004;104:2940-2.
Sasaki M, Suzuki H, Ito K, Abe T, Sugiyama Y. Transcellular transport of organic anions across a double-transfected madin-darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2). J Biol Chem 2002;277:6497-503.
Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, et al. Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS 2002;16:2295-301.
Guo A, Marinaro W, Hu P, Sinko PJ. Delineating the contribution of secretory transporters in the efflux of etoposideusing Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos 2002;30:457-63.
Cannon JB, Long MA. Emulsions, microemulsions, and lipid-based drug delivery systems for drug solubilization and delivery, Part II: oral applications. In: Liu R. editor. Water-insoluble drug formulation. 2nd ed. Boca Raton FL: CRC Press; 2008. p. 227-54.
Zhou S, Chan E, Lee YL, Boelsterli UA, Li SC, Wang J, et al. Therapeutic drugs that behaveasmechanism-based inhibitors of cytochrome P450 3A4. A Curr Drug Metab 2004;5:415-42.
Hochman JH, Chiba M, Nishime J, Yamazaki M, Lin JH. Influence of P-glycoprotein on the transport and metabolism of indinavir in caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther 2000;292:310-8.
Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm 1994;106:15-23.
Zangenberg NH, Mullertz A, Kristensen HG, Hovgaard L. A dynamic in vitro lipolysis model I. Controlling the rate of lipolysis by continuous addition of calcium. Eur J Pharm Sci 2001;14:115-22.
Zangenberg NH, Mullertz A, Kristensen HG, Hovgaard L. A dynamic in vitro lipolysis model II: evaluation of the model. Eur J Pharm Sci 2001;14:237-44.
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;23:2165-74.
Edwards GA, Porter CJH, Caliph SM, Khoo SM, Charman WN. Animal models for the study of intestinal lymphatic drug transport. Adv Drug Delivery Rev 2001;50:45-60.
Griffin BT, O'Driscoll CM. A comparison of intestinal lymphatic transport and systemic bioavailability of saquinavir from three lipid-based formulations in the anaesthetized rat model. J Pharm Pharmacol 2006;58:917-25.
Dahan A, Hoffman A. Enhanced gastrointestinal absorption of lipophilic drugs. In: Touitou E, Barry BW. editors. Enhancement in drug delivery. 1st ed. Florida: CRC Press; 2006. p. 111-27.
Mueller EA, Kovarik JM, Bree JBV, Grevel J, Lucker PW, Kutz K, et al. Influences of a fat-rich meal on the pharmacokinetics of a new oral formulation of cyclosporine in a crossover comparison with the market formulation. Pharm Res 1994;11:151-5.
Dahan A, Hoffman A. The effect of different lipid-based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. Eur J Pharm Biopharm 2007;67:96-105.
Dressman JB, Reppas C. In vitro in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci 2000;11 Suppl 2:S73-80.
Seeballuck F, Ashford MB, Driscoll CMO. The effects of pluronic block copolymers and cremophor EL on intestinal lipoprotein processing and the potential link with p-glycoprotein in caco-2 cells. Pharm Res 2003;20:1085-92.
Khoo SM, Shackleford DM, Porter CJH, Edwards GA, Charman WN. Intestinal lymphatic transport of halofantrine occurs after oral administration of a unit-dose lipid-based formulation to fasted dogs. Pharm Res 2003;20:1460-5.
Petri N, Bergman E, Forsell P, Hedeland M, Bondesson U, Knutson L, et al. First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model. Drug Metab Dispos 2006;3:1182-9.
Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos 1995;16:351-80.
Cole ET, Cade D, Benameur H. Challenges and opportunities in the encapsulation of liquid and semi-solid formulations into capsules for oral administration. Adv Drug Delivery Rev 2008;60:747-56.
Ito Y, Arai H, Uchino K, Iwasaki K, Shibata N, Takada K. Effects of adsorbents on the absorption of lansoprazole with a surfactant. Int J Pharm 2005;289:69-77.
Madhavi K, Shikha A, Suresh B. Formulation and in vitro characterization solid self-emulsifying drug delivery system of ramipril prepared by adsorption technique. Int J Curr Pharm Res 2016;8:40-5.
Shweta K, Yogesh P. Formulation and evaluation of neusilin us2 adsorbed amorphous solid self-micro emulsifying delivery system of atorvastatin calcium®. Asian J Pharm Clin Res 2016;9:93-100.
Naser MY Hasan, Dhaifallah M Almalki, Mohammed JK Althuwaybi, Hassan M Alshehri. SMEDDS tablet: compatibility of solid SMEDDS using various pharmaceutical tablet excipients. Int J Pharm Pharm Sci 2016;8:246-51.
Ronak Savla, Jeff Browne, Vincent Plassat, Kishor M Wasan, Ellen K Wasan. Review and analysis of FDA approved drugs using lipid-based formulations. Drug Dev Ind Pharm 2017;43:1743-58.
Published
How to Cite
Issue
Section
