• NASER M. Y. HASAN School of Pharmacy, Applied Science Private University, Jordan


Objective: Evaluation of the self-emulsifying behaviour of type III lipid systems comprising mixed medium chain glycerides (Miglyol 812-Imwitor 988) and wide range of hydrophilic surfactants in an attempt to identify self-emulsifying microemulsion formulations, prevaricate the crystallization tendency of Cremophor RH40 in the pre-microemulsion concentrate, to shed some light on the mechanistic behavior of these systems after aqueous dispersion.

Methods: Non-ionic surfactants with HLB in the range 14 to 16.5 are investigated amongst these are; Cremophor RH40, Cremophor EL, Crillet 4 (polysorbate 80), Crillet 1 (polysorbate 20) and Tagat O2. Optimum oil blends of Miglyol 812-Imwitor 988 and various non-ionic surfactant systems were verified using self-emulsification performance studies, oil droplet diameter measurements and dynamic equilibrium phase studies.

Results: Oil blends of Miglyol 812 as an oil and Imwitor 988 as a cosurfactant were optimized for microemulsion systems at ratios of 1:1 in the case of Cremophor RH40 or EL, and at 2:3 in the case of Crillet 4 or Tagat O2. In order to obtain small droplet size and fast dispersion rate for type III lipid systems, hydrophilic surfactants with HLB values between 13 and 15 were found to be the optimum.

Conclusion: Spontaneous micro-emulsification in type III lipid system was attributed to the “diffusion and stranding” theory. Yet, the formation of liquid crystalline phases as intermediate phases during dilution of the oil formulation with water appears to be quintessential for the mechanistics of emulsification regardless type of lipid class system.

Keywords: SEDDS, SMEDDS, Lipid formulations, Medium chain mono-and glycerides, Poorly water-soluble compounds


1. Shah NH, Carvajal MT, Patel CI, Infeld MH, Malick AW. Self-emulsifying drug delivery system (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm 1994;106:15-23.
2. Farah N, De Teddeo M, Larfret JP, Denis J. Self-microemulsifying drug delivery system for improving in vitro dissolution of drugs. AAPS Annual Meeting Orlando, FL; 1993.
3. Hasan MYN. Self-micro-emulsifying lipid formulations to improve the bioavailability of poorly water-soluble drugs. Ph. D. thesis, University of Bath; 2004.
4. Hasan NM. Role of medium-chain fatty acids in the emulsification mechanistics of self-micro-emulsifying lipid formulations. Saudi Pharm 2014;22:580-90.
5. Hasan NMY, Hayajneh FM, Khaleel MA, Alharthi SA, Shahada HM, Almalki HF. Development of potential self-microemulsifying lipid formulation for the oral administration of curcumin. Int J Adv Pharm Biol Chem 2015;4:590-602.
6. Mohsin K. Design of lipid-based formulations for oral administration of poorly water-soluble drug fenofibrate: effect and digestion. AAPS Pharam Sci-Tech 2012;13:637-47.
7. Savla R, Browne J, Plassat V, Wasan KM, Wasan EK. Review and analysis of FDA approved drugs using lipid-based formulations. Drug Dev Ind Pharm 2017;43:1743-58.
8. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. Eur J Pharm Sci 2000;11:93-8.
9. 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.
10. Tung NT, Tran CS, Pham TM, Nguyen HA, Nguyen TL, Chi SC, et al. Development of solidified self-microemulsifying drug delivery systems containing l-tetrahydropalmatine: design of experiment approach and bioavailability comparison. Int J Pharm 2018;537:9-21.
11. Bhattacharya S, Mishra S, Prajapati BG. Design and development of docetaxel solid self-microemulsifying drug delivery system using principal component analysis and d-optimal design. Asian J Pharm 2018;12:122-44.
12. Chen ZQ, Liu Y, Zhao JH, Wang L, Feng NP. Improved oral bioavailability of poorly water-soluble indirubin by a supersaturatable self-microemulsifying drug delivery system. Int J Nanomed 2012;7:1115-25.
13. Pattewar S, Kasture SB, Pande VV, Patil DN, Sharma SK. Development and optimization of piroxicam-loaded solid self-microemulsifying drug delivery system. Indian J Pharm Sci 2018;80:350-8.
14. Shah A, Thool P, Sorathiya K, Prajapati H, Dalrymple D, Serajuddin ATM. Effect of different polysorbates on the development of self-microemulsifying drug delivery systems using medium chain lipids. Drug Dev Ind Pharm 2018;44:215-23.
15. Shah AV, Desai HH, Thool P, Dalrymple D, Serajuddin ATM. Development of self-microemulsifying drug delivery system for oral delivery of poorly water-soluble nutraceuticals. Drug Dev Ind Pharm 2018;44:895-901.
16. Shukla A, Janich M, Jahn K, Krause A, Kiselev MA, Neubert RHH. Investigation of pharmaceutical Oil/water microemulsions by small-angle scattering. Pharm Res 2002;19:881-6.
17. Suman K, Chandrasekhar P, Balaji S. Approaches for the development of solid self-emulsifying drug delivery systems and dosage forms. Asian J Pharm Sci 2009;4:240-53.
18. Levy JM, Benita S. Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation model. Int J Pharm 1990;66:958-64.
19. Kommuru TR, Gurley M, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm 2001;212:233-46.
20. Gao ZG, Choi HG, Shin HJ, Park KM, Lim SJ, Hwang KJ, et al. Physicochemical characterization and evaluation of a microemulsion system for oral delivery of cyclosporin A. Int J Pharm 1998;161:75-86.
21. Lawrence MJ, Microemulsions as drug delivery vehicles. Curr Opin Colloid Interf Sci 1996;1:826-32.
22. Kale NJ, Allen LV. Studies on microemulsions using Brij 96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants. Int J Pharm 1989;57:87-93.
23. Eccleston GM. Microemulsions. Edited by Swarbrick S, Boylan JC. Encyclopedia of pharmaceutical technology. Marcel Dekker, New York; 1992. p. 375-421.
24. Kawakami K, Yoshikawa T, Moroto Y, Kanaoka E, Takahashi K, Nishihara Y, et al. Microemulsion formulation for enhanced absorption of poorly soluble drugs: I. prescription design. J Controlled Release 2002;81:65-74.
25. Kawakami K, Yoshikawa T, Hayashi T, Nishihara Y, Masuda K. Microemulsion formulation for enhanced absorption of poorly soluble drugs: II. In vivo study. J Controlled Release 2002;81:75-82.
26. Lu JR, Su TJ, Lawrence MJ, Barlow DJ, Warisnoichareon W, Zuberi T. The and composition of ethyl hexadeconate layers spread on aqueous solution of hexaethylene glycol monododecyl ether. J Phys Chem B 1999;103:4638-48.
27. Kunieda H, Horii M, Koyama M, Sakamoto K. Solubilisation of polar oils in surfactant self-organized structures. J Colloid Intref Sci 2001;236:78-84.
28. Chen Y, Li G, Wu X, Chen Z, Hang J, Qin B, et al. Self-microemulsifying drug delivery system (SMEDDS) of vinpocetine: formulation development and in vivo assessment. Biol Pharm Bull 2008;31:118-25.
29. Hasan NMY, SH Moss SH, Pouton CW. The choice of non-ionic surfactant in self-micro-emulsifying lipid formulations for the oral delivery of poorly water-soluble compounds. J Pharm Pharmacol 2005;57:S53.
30. Wakerly MG. Self-emulsifying drug delivery systems based on nonionic surfactant-oil mixtures. Ph. D. Thesis, University of Bath; 1989.
31. Pouton CW. A study of self-emulsifying oil/surfactant mixtures. PhD thesis, University of London; 1982.
32. Rang MJ, Miller CA. Spontaneous emulsification of oil droplets containing surfactants and medium-chain alcohols. Prog Colloid Polym Sci 1998;109:101-7.
33. Rang MJ, Miller CA. Spontaneous emulsification of oils containing hydrocarbon, Nonionic surfactant, and oleyl alcohol. J Colloid Interface Sci 1999;209:179-92.
34. Lin TJ, Kurihara H, Ohta H. Prediction of optimum o/w emulsification via solubilization measurements. J Soc Cosmet Chem 1977;28:457-79.
35. Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Delivery Rev 1997;25:47-58.
36. Pouton CW, Wakerly MG, Meakin BJ. Self-emulsifying systems for oral delivery of drugs. Proc Int Symp Controlled Release Bioact Mater 1987;14:113-4.
37. Wakerly MG, Pouton CW, Meakin BJ, Morton FS. Self-emulsification of vegetable oil-nonionic surfactant mixtures: a proposed mechanism of action. ACS Symp Ser 1986; 311:242-55.
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