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Author for Correspondence:Nandini Chauhan,Faculty of Pharmacy,214-Rajpur Road,Dehradun, India-248009.E-mail: chauhannandini0777@gmail.com

Review Article

ISSNPrint 2231 – 3648

Online 2231 – 3656

Available Online at: www.ijpir.com

SELF EMULSIFIED DRUG DELIVERY SYSTEM: A REVIEW*Nandini Chauhan, Himansu Chopra

Faculty of Pharmacy, GRD (PG) IMT, 214-Rajpur Road, Dehradun, India.__________________________________________________________________________________AbstractOral route is the easiest and most convenient route for drug administration. The major problem in oral drugformulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may leadto high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The dissolution isthe rate limiting step in their absorption and oral bioavailability. Self-emulsifying drug delivery systems(SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble or lipophilicdrugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yieldingmicro- or nanoemulsions containing the solubilized drug. In particular SEDDS is isotropic mixture of lipids,surfactant and cosurfactant that can disperse spontaneously in aqueous media and form fine emulsion. Thisreview includes the current research and development in the field of SEDDS with emphasis of excipients,formulation aspects and characterization.

Keywords: SEDDS, lipids, surfactants and co surfactants.

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IntroductionApproximately 40% of new drug candidates havepoor water solubility and the oral delivery of suchdrugs is frequently associated with lowbioavailability. Various formulation strategies areexploited including the use of surfactants, lipids,permeation enhancers, micronisation, saltformation, cyclodextrins, nanoparticles and soliddispersions[1,2]. Self emulsifying drug deliverysystem (SEDDSs) have gained exposure for theirability to increase solubility and bioavailability ofpoorly soluble drugs. SEDDSs are isotropicmixtures of oils and surfactants; sometimes itcontains co-solvents and it can be used for thedesign of formulations in order to improve the oralabsorption of highly lipophilic compounds[3]. On

dilution by an aqueous phase they form fine stableoil-in-water (o/w) emulsions or fine lipid dropletswhich is the characteristic feature of these systems.When such a formulation is released into the lumenof the GIT, it disperses to form a fine emulsiongenerally o/w emulsion, so that the hydrophobicdrug get remain in solution in the GIT whichavoids the dissolution step. Dissolution step is therate limiting step in the absorption of poorly water-soluble drugs[4]. The size of droplets rangesapproximately less than 100 nm. SEDDS areprepared in two forms liquid and solid. SEDDScan be prepared by solidification of liquidself-emulsifying components into powder. Thispowder is then used to produce various solid

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dosage forms, for example self-emulsifyingpellets, self-emulsifying tablets etc[5-8]. In manystudies it have been reported that SEDDS are usedfor delivering and targeting hydrophobic drugssuch as coenzyme Q10, halofantrine, vitamin E andcyclosporine-A[9-12]. Recently, SEDDS have beenformulated using medium chain tri-glyceride oilsand nonionic surfactants, the latter being less toxic.The process of self-emulsification proceedsthrough formation of liquid crystals (LC) and gelphases. Release of drug from SEDDS is highlydependent on LC(liquid crystal) formed at theinterface, since it is likely to affect the angle ofcurvature of the droplet formed and the resistanceoffered for partitioning of drug into aqueousmedia[13]. Due to its small globule size, themicro/nanoemulsifed drug can easily be absorbedthrough lymphatic pathways, thereby bypassing thehepatic first-pass effect[14]. Factors affecting the invivo performance of SEDDS include their ability toform small droplets of oil (<5mm) and the polarityof the oil droplets to promote faster drug releaseinto aqueous phase[15]. The smaller oil droplets

provide a large inter- facial area for pancreaticlipase to hydrolyze triglycerides and therebypromote the rapid release of the drug and/orformation of mixed micelles of the bile saltscontaining the drug[16].

Criteria of Drug SelectionBCS (Bio-pharmaceutical classification system)classifies the drug based on solubility and‘permeability of a drug (Table 1:Biopharmaceutical Classification of Drugs).Mainly Class 2 (Low Solubility, HighPermeability) is used for SEDDS. A primarycandidate may be selected by assessing the druglipophilicity (lop P) value and its solubility inpharmaceutical manufacturing grade lipidexcipients which dissolve entire amount of dose ofdrug to be administered. Log P is the primarycriteria and high log P value greater than 4 isdesirous for lipidic systems. Another parametersthat play important role are melting point and dose.Low melting point and low dose are required fordevelopment of lipidic systems[17].

Table No. 01: Biopharmaceutical Classification of DrugsClass Solubility Permeability Absorption pattern Rate-Limiting Step in Absorption

1 High High Well absorbed Gastric emptying2 Low High Variable Dissolution3 High Low Variable Permeability4 Low Low Poorly absorbed Case by case

Composition of SEDDSThe self emulsifying process depends on[18]

The nature of the oil–surfactant pair. The surfactant concentration. The temperature at which self-

emulsification occurs.

1. OilsOils can solubilize the lipophilic drug in aspecific amount. It is the most importantexcipient because it can facilitate self-emulsification and increase the fraction oflipophilic drug transported via the intestinallymphatic system, thereby increasingabsorption from the GI tract. Long-chaintriglyceride and medium-chain triglyceride oilswith different degrees of saturation have beenused in the design of SEDDSs. Modified orhydrolyzed vegetable oils have contributedwidely to the success of SEDDSs owing totheir formulation and physiologicaladvantages. Novel semi synthetic medium-

chain triglyceride oils have surfactantproperties and are widely replacing the regularmedium-chain triglyceride (Table 2:Excipients for SEDDS).

2. SurfactantNonionic surfactants with highhydrophiliclipophilic balance (HLB) valuesare used in formulation of SEDDSs (e.g.,Tween, Labrasol, Labrafac CM 10,Cremophore etc.). The usual surfactantstrength ranges between 30–60% w/w of theformulation in order to form a stable SEDDS.Surfactants have a high HLB andhydrophilicity, which assists the immediateformation of o/w droplets and/or rapidspreading of the formulation in the aqueousmedia. Surfactants are amphiphilic in naturethey can dissolve or solubilise relatively highamounts of hydrophobic drug compounds.This can prevent precipitation of the drug

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within the GI lumen and for prolongedexistence of drug molecules.

3. Co-surfactants/Co-solventsFormulation of effective SEDDSs requireshigh concentration of surfactants, co-surfactant/Cosolvents like span, capyrol 90, capmul,lauroglycol, diethylene glycol.

Table No. 02: Excipients for SEDDS

Oil Surfactants Co- surfactants/Co-solvents

Cotton seed oil Polysorbate 20(tween20) Span 20Soybean oil Polysorbate 80(tween 80) Span 80Corn oil D-alpha Tocopheryl polyethylene glycol 1000 succinate (TPGS) Capryol 90Sunflower oil Polyoxy-35- castor oil (cremophor RH40) LauroglycolCaster oil Polyoxy-40-hydrogenated castor oil (cremophor RH40) TranscutolSesame oil Labrasol Isopropyl alcoholPeanut oil EthanolLabrafac Polyethylene glycol

Formulation developmentSolubility ScreeningThe first and foremost step in designing a lipidformulation is to assess the solubility of the leadcompound in various lipid excipients, cosolvents,and surfactants. Since the clinical dose is usuallyunknown in early discovery, a general rule ofthumb is that solubility in a range of 25−50 mg/mLin lipid excipients is needed to support futurestudies. The solvent capacity of lipids can beincreased by addition of cosolvents and surfactants.The incorporation of cosolvents and surfactants canalso help to reduce the interfacial tension and theoil−water partition coefficient and therefore canfacilitate emulsification and effective absorption[19].

Designing of formulation[19]

Lipid formulation classification system proposedby Pouton and Porter.[18, 27] On the basis of thissystem in which lipid formulations are classifiedinto three categories, one can start with simple lipidsolutions without surfactants (type I). If the wholedose cannot be solubilized in the lipid solution in atypical unit dosage form (e.g., 0.5-1.0 mL), thenthe option could be either type II formulationscontaining oils and water insoluble surfactants ortype III formulations which are mixtures of oils,surfactants, and cosolvents.

The properties of lipid excipients such as the fattyacid chain length have been shown to affect lipiddigestion and drug solubilization. In general, themedium-chain glycerides tend to work well withless lipophilic compounds that can be readilytransferred to the highly solubilizing aqueous

environment after lipid digestion. The long chainglycerides, on the other hand, prefer highlylipophilic compounds that would either remain inthe undigested oil phase or partition into mixedmicelles after digestion.

Mechanism of self emulsificationThe exact mechanism behind the self-emulsification is not clearly known. According to‘Reiss’, self-emulsification occurs when theentropy change that favours dispersion is greaterthan the energy required to increase the surfacearea of the dispersion. The free energy of theconventional emulsion is a direct function of theenergy required to create a new surface betweenthe oil and water phases. It can be represented byfollowing equation:ΔG = ΣN π r2σWhere,G- is the free energy,N -is the number of droplets of radiusr and σ indicates the interfacial energy[20-22].

According to “Wakerly et al”, the addition of abinary mixture to water, results in interfaceformation between the oil and aqueous continuousphases, followed by the solubilisation of waterwithin the oil phase owing to aqueous penetrationthrough the interface. This process will occur untilthe solubilisation limit is reached close to theinterface[23, 24].

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Characterization of SEDDS1) In vitro Dispersion Test

The in vitro dispersion test offers a quickassessment of lipid emulsification and drugsolubilization in the stomach. It can be used asthe first-tier assay for screening lipidformulations at early stages of drug discoverywhen resources and compound supply arelimited. It is conducted by diluting the lipidformulation in water or simulated gastric fluidat different dilution ratios. At predeterminedtime points, the dispersion is examinedvisually for the formation of an emulsion ormicroemulsion and the particle size of the oildroplets can be measured by laser lightdiffraction or photon correlation spectroscopy.The drug solubilization can be quantified byHPLC analysis of drug concentration in theaqueous phase[25].

2) In vitro Lipid Digestion TestThe in vitro digestion test is a useful tool forassessing solubilization and absorptionpotential of a lipid formulation in the smallintestine. It helps formulation scientists tobetter understand the efficiency of drugtransfer from oil phase to aqueous phase, theamount of drug available in aqueous phase forabsorption, and the precipitation potential ofthe compound in the GI tract. To conduct thetest, the lipid formulation is first dispersed in adigestion buffer containing bile salts andphospholipids, followed by addition ofpancreatic lipase and co-lipase to initiate thedigestion. At a predetermined time, samplesare collected and ultracentrifuged into a poorlydispersed oil phase (containing undigested TGand DG), a highly dispersed aqueous phase(containing solubilized drug as well as bilesalts, MG, and FA) and a precipitated pelletphase (containing precipitated drug andundissolved bile salts). The drug concentrationin each phase can then be quantified by HPLCanalysis[26].

3) Ternary Phase DiagramPseudo-ternary phase diagrams are studied fordevelopment of SEDDS. It helps in accessingthe optimum concentration of differentexcipients necessary to obtain homogenousself emulsification ability and drug loading.Once the appropriate microemulsion

components have been selected, ternarypseudo phase diagram was constructed todefine the extent and nature of themicroemulsion regions[27].

4) Droplet SizeDroplet size is critical factor in selfemulsification performance because itdetermines the rate and extent of drug releaseas well as absorption. It is measured bydynamic light intensity to measure the velocityof the Brownian diffusion and consequentlythe dispersed droplets. Photon correlationspectroscopy, microscopic techniques or acoulter Nanosizer are mainly employed for thedetermination of the emulsion droplet size.Particle size distribution can be further verifiedby cryogenic transmission electron microscopy(cryo-TEM). For cryo-TEM studies, samplesare prepared in a controlled environmentverification system. A small amount of sampleis put on carbon film supported by a coppergrid and blotted by filter paper to obtain thinliquid film on the grid. The grid is quenched inliquid ethane at -180 UC and transferred toliquid nitrogen at -196 UC. Cryo-TEM offersthe advantage of visualizing the size as well asshape. Small-angle neutron scattering andsmall-angle X-ray scattering can also be usedto obtain information on the size and shape ofthe droplets.

5) Zeta PotentialThis is used to identify the charge on droplets.The charge on the oil droplets in conventionalSMEDDS is negative due to the presence offree fatty acids; however, incorporation of acationic lipid, such as oleylamine at aconcentration range of 1-3% will yield cationicSMEDDS. Zeta potential helps to predict thestability and flocculation effect in emulsionsystem. If the zeta potential falls below acertain level, colloid will aggregate due toattractive forces. Conversely, a high zetapotential maintains a stable system.

6) Conductivity testConductivity measurements are able todetermine the point of aqueous phase additionwhere the system changes from oil continuousto a water continuous phase. It also helps inmonitoring phase inversion phenomena.

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7) Turbidity measurementThis identifies efficient self emulsification byestablishing whether the dispersion reachesequilibrium rapidly and in a reproducible time.The measurements are carried out on turbiditymeters.

List of drugs currently incorporated in SEDDSA lot of drugs recently found to be incorporated inSEDDS as per the available literature. Wesummarized recent research in Table 3: Drugsrecently incorporated in SEDDS. Thebioavailability improvement, enhanced solubilityand dissolution were the major advantagesachieved by the researchers.

Table No. 03: Drugs recently incorporated in SEDDS

S.no Drug AuthorType of

formulation Inference

1. Amphotericin B[28] Bhattacharyya A(2012)

SEDDS Increased the solubility and dissolution ofAmphotericin B

2. Atorvastatin[29] Fariba KHAN(2012) SEDDS Dissolution of ATV can successfully be enhanced

3. Ciprofloxacin[30] BAKSHIMADHURA,(2013)

SMEDDS (selfmicro emulsifyingdrug deliverysystem)

Significant improvement indrug solubility, absorption rate of ciprofloxacin

4. Efavirenz[31] V. KIRANKUMAR (2013) Solid SEDDS

Enhance solubility and dissolution of sparinglysoluble compounds like Efavirenz

5. Gliclazide[32] Vikrant Wankhade(2012)

SNEDDS (Selfnano- emulsifieddrug deliverysystem)

Concentration of oil present in the formulationhaving greater impact on surfactant and co-surfactantwhich reduces the particles size in the effectiveranges. They obtain an optimum formulation withparticle size 145.8 nm

6. Ibuprofen[33] Sadika Akhter(2012)

SEDDSIncreased dissolution for poorly water soluble drugIbuprofen

7. Indomethacin[34] Nicholas C. Obitte(2013)

Solid SEDDS Improving the in vitro and corresponding anti-inflammatory properties of indomethacin.

8. Irbesarten[35] Jaydeep Patel(2011)

Self nano-emulsifying drugdelivery system

IRB showed a significant increase in the dissolutionrate and oral absorption

9. Nimodipin[36] Amit A. Kale(2008)

SEDDS Improve in vitro and in vivo performance ofnimodipine,

10. Tacrolimus[37] Pranav V Patel(2013) Solid SMEDDS

Improved emulsification properties and goodthermodynamic stability

11. Valsartan[38] Gupta A.K. (2011) SEDDS Increased dissolution rate

Marketed Formulations of SEDDSThe current scope of SEDDS is shown by theavailable marketed commercial products. We

summarized a list of marketed formulationavailable worldwide in Table 4: MarketedFormulations of SEDDS[39-43].

Table No. 04: Marketed Formulations of SEDDSBrand name Drug used Dosage form Company

Neoral Cyclosporine SGC (soft gelatin capsule) Novartis

Norvir Ritonavir SGC Abott laboraties

Fortovase Saquinavir SGC Hoffmann roche

Agenerase Amprenavir SGC GSK

Convulex Volporic acid SGC Pharmacia

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ConclusionAn increasing number of drug candidatesdiscovered in recent years are highly lipophiliccompounds with poor aqueous solubility. Selfemulsifying drug delivery system is a promisingapproach in bioavailability enhancement of poorlywater soluble drugs. The increasing interest andavailability of literature now make it possible toproduce clinically effective commercialformulations using such approach. Selection ofexcipients with utmost care and understanding ofbiopharmaceutical aspects are helpful in designingof stable formulation. The efficiency of system iscase specific, thus proper characterization shouldbe performed. The preclinical evaluation andclinical evaluation can be connected early in theprocess, which significantly reduce the formulationdevelopment time and increases the overall successpotential of a clinically viable formulation.

References1. Gursoy RN, Benita S Self emulsifying drug

delivery systems for improved oral delivery oflipophilic drugs: Biomedicine andPharmacotherapy 2004; 58:173-182.

2. Abdalla A, Klein S, Mader K A New Selfemulsifying drug delivery system for poorlysoluble drugs. European Journal ofPharmaceutical Sciences 2008; 35:357-464.

3. Bhatt PP Osmotic Drug Delivery Systems forPoorly Soluble Drugs. The Drug DeliveryCompanies Report Autumn/Winter 2004; 26-29. (Pharma Ventures Ltd 2004).

4. Hauss DJ Oral lipid-based formulations:Advanced Drug Delivery Reviews 2007;59(7): 667-676.

5. Attama AA, Nzekwe IT, Nnamani PO,Adikwu MU, Onugu CO The Use of Self-Emulsifying System in the Delivery ofDiclofenac: International Journal ofPharmaceutics 2003; 262(1-2):23-28.

6. Nazzal S, Nutan M, Palamakula A, Shah R,Zaghloul AA and Khan MA Optimization of aSelf-Nanoemulsified Tablet Dosage Form ofUbiquinone Using Response SurfaceMethodology: Effect of FormulationIngredients. International J. Pharmaceutics2002; 240(1-2): 103-114.

7. Abdalla A, Mader K Preparation andCharacterization of a Self emulsifying PelletFormulation. European Journal ofPharmaceutics and Biopharmaceutics2007;66(2): 220-226.

8. Franceschinis E, Voinovich D, Grassi M,Perissutti B, Filipovic-Grcic J, Martinac A,Meriani-Merlo F Self-Emulsifying PelletsPrepared by Wet Granulation in High-ShearMixer: Influence of Formulation Variables andPreliminary Study on the In Vitro Absorption.International Journal of Pharmaceutics 2005;291(1-2): 87-97.

9. Kommuru TR, Gurley B, Khan MA and ReddyIK Self Emulsifying Drug Delivery Systems(SEDDS) of Coenzyme Q10: FormulationDevelopment and Bioavailability Assessment.International J. Pharmaceutics 2001; 212(2):233-246.

10. Julianto T, Yuen KH and Noor AM ImprovedBioavailability of Vitamin E with a Self-Emulsifying Formulation. International Journalof Pharmaceutics 2000; 200(1): 53-57.

11. Khoo SM, Humberstone AJ, Porter CJH,Edwards GA, Charman WN FormulationDesign and Bioavailability Assessment ofLipidic Self-Emulsifying Formulations ofHalofantrine. International J. Pharmaceutics1998; 167(1-2): 155-164.

12. Gao ZG, Choi HG, Shin HJ, Park KM, Lim SJ,Hwang KJ, Kim CK PhysicochemicalCharacterization and Evaluation of aMicroemulsion System for Oral Delivery ofCyclosporine A. International J. Pharmaceutics1998; 161(1): 75-86.

13. Serajuddin ATM, Sheen PC, Mufson D,Bernstein DF, Augustine MA Effect of vehicleamphiphilicity on the dissolution andbioavailability of a poorly water- soluble drugfrom solid dispersion, J. Pharm. Sci. 1988;77(5): 414-417.

14. R Sunitha, SD Satya and MVL Aparna NovelSelf-emulsifying Drug Delivery System- Anapproach to enhance bioavailability of poorlywater soluble drugs.International Journal ofResearch in Pharmacy and Chemistry2011;1(4): 828- 838.

45Nandini Chauhan. et al., Int. J. Pharm & Ind. Res., Vol.–04 (01) 2014 [39 - 46]

www.ijpir.com

15. Shah NH, Carvajal MT, Patel CI, Infeld MH,Malick AW Self-emulsifying drug deliverysystems (SEDDS) with polyglycolyzedglycerides for improving in vitro dissolutionand oral absorption of lipophilic drugs. Int JPharm, 1994; 106 (1) 15–23.

16. New RRC, Kirby CJ, Solubilisation aids, 1999,US Patent 5968549.

17. Brahmankar DM, Jaiswal SBBiopharmaceutical and Pharmacokinetics aTreatise 2011;29.

18. Murdandea SB, Gumkowskia MJDevelopment of self-emulsifying formulationsthat reduces the food effect for torcetrapib. IntJ Pharm 2008; 351: 15-22.

19. Chen XQ, Gudmundsson OS and Hageman MJapplication of lipid-based formulation in drugdiscovery. Journal of medicinal chemistry2012;55:7945-7956.

20. Constantinides PP Lipid microemulsion forimproving drug dissolution and oralabsorption: physical and biopharmaceuticalaspects, Pharm. Res1995; 12 Suppl 11;1561.72.

21. Shah NH, Carvajal MT, Patel CI SEDDS withpolyglycolized glycerides for improving invitro dissolution and oral absorption oflipophilic drugs. Int. J Pharm 1994; 106: 115-123.

22. Riess H Entropy induced dispersion of bulkliquids, J. Colloids Interface Sci1975;53: 61-70.

23. Jing-ling Tang, Jin Sun and Zhong-Gui HeSelf-Emulsifying drug delivery systems:Strategy for improving oral delivery of poorlysoluble drugs. Current drug therapy 2007; 2:85- 93.

24. Vasanthavada M and Serajuddin ATM Lipidbased self emulsifying solid dispersions.Informa Healthcare 2007; 149-184.

25. Devani MJ, Ashford M, Craig DQM. Theemulsification and solubilisation properties ofpolyglycolysed oils in self-emulsifyingformulation. J. Pharm. Pharmacol. 2004;56:307-316.

26. Porter CJH and Charman WN In vitroassessment of oral lipid based formulation.Adv. Drug Delivery Rev. 2001; 50:S127-S147.

27. Sarpal K, Pawar YB and Bansal AK Self-emulsifying drug delivery system: A strategyto improve oral bioavailability. Currentresearch & information on pharmaceuticalssciences 2010;11(3):42-49.

28. Bhattacharyya A, Bajpai M Development andevaluation of a self-emulsifying drug deliverysystem of amphotericin-B. Asian JPharm.2012;6:124-129.

29. Khan F, Islam MS, Roni MA, Jalil RUSystematic Development of Self-EmulsifyingDrug Delivery Systems of Atorvastatin withImproved Bioavailability Potential. Sci Pharm2012; 80:1027-1043.

30. Bakshi M, Mahajan SC, Bhandari GFormulation Design and Evaluation of Selfmicroemulsifying Drug Delivery System ofCiprofloxacin. IJPRBS 2013; 2(1):29-53.

31. Kumar VK, Devi MA and BhikshapathiDVRN Development of solid Self EmulsifyingDrug Delivery System Containing Efavirenz:Invitro and in vivo Evaluation. Int J Pharm BioSci 2013 ; 4(1): 869 – 882.

32. Vikrant P Wankhade, Atram SC, Nishan NBobade, Srikant D Pande, Kiran K TaparFormulation and optimization of SNEDDS ofgliclazide using response surfacemethodology. Asian J Pharm 2012;6: 289-94.

33. Akhter S, Hossain MI Dissolutionenhancement of Capmul PG8 and CremophorEL based Ibuprofen Self Emulsifying DrugDelivery System (SEDDS) using Responsesurface methodology. International CurrentPharmaceutical Journal 2012;1(6):138-150.

34. Obitte NC, Ofokansi KC, Chime SA, EbeleIdike Solid self-emulsifying drug deliverysystem based on a homolipid and vegetableoil: A potential vehicle for the delivery ofindomethacin a disadvantaged drug.International Journal of Green Pharmacy2013;73: 244-251.

35. Patel J, Patel A, Raval M, Sheth NFormulation and development of a self-nano-emulsifying drug delivery system of irbesartan.Journal of Advanced PharmaceuticalTechnology & Research 2011;2(1):9-16.

36. Kale A A and Patravale VB Design andEvaluation of self-Emulsifying Drug DeliverySystem (SEDDS) of Nimodipin. AAPSPharmSciTech 2009;9(1):191-196.

46Nandini Chauhan. et al., Int. J. Pharm & Ind. Res., Vol.–04 (01) 2014 [39 - 46]

www.ijpir.com

37. Patel HK, Misan CK, Mehta DS, PatelMB Development and characterization ofliquid and solid self- microemulsifying drugdelivery system of Tacrolimus. Asian J Pharm2012;6:204-211.

38. Gupta AK, Mishra DK and Mahajan SCPreparation and in-vitro evaluation of selfemulsifying drug delivery system ofantihypertensive drug valsartan. Int. J. ofpharm. & Life Sci.2011;2(3):633-639.

39. Morozowich W, Gao P Developing solid oraldosage forms Pharmaceutical theory andpractice improving the oral absorption ofpoorly soluble drugs using SEDDS and S-SEDDS formulations 2009; 19: 443-468.

40. Gershanik T, S Benita Positively charged selfemulsifying oil formulation for improving oralbioavailability of progesterone. Pharm DevTechnol 1996;1: 147-157.

41. Hauss DJ Oral Lipid-based formulations. AdvDrug Deliv Rev2007; 59: 667-676.

42. Strickley RG Currently marketed oral lipid-based dosage forms drug products andexcipients in DJ Hauss care Inc New York 2,Oral lipid-based formulations enhancing thebioavailability of poorly water soluble drugs.Informa health 2007.

43. Strickley RG Solubilizing excipients in oraland injectable formulations. Pharm Res 2004;2: 201-230.