• Naser M. Y. Hasan School of Pharmacy, Applied Science Private University, Jordan


Objective: Parameters in the oil pre-concentrate which can affect the solvent capacity of the resultant dispersion such as, oil-cosurfactant ratio, type of surfactant used in the system, the inclusion of water soluble co-solvents and the solubilization capacity of native surfactants such as, bile salts and lecithin were studied in an attempt to circumvent crystallization of drug during its passage in the gut.

Methods: Different types of self-emulsifying systems representing type II, IIIA and IIIB, were used to probe the influence of the various physicochemical properties of the resultant dispersions on the fate of dissolved model lipophilic drug. This was achieved by studying emulsification behavior of lipid systems in fed and fasted biological fluids, analyzing solubilization/drug crystallization kinetics and oil droplet diameter measurement.

Results: Self-micro-emulsifying lipid systems lost solvent capacity on dispersion and were not able to keep the drug in solution at equilibrium. Miglyol 812/Imwitor ratio in the pre-concentrate mixture appeared to influence the kinetics of drug crystallization. Pre-microemulsion systems containing Tagat TO dispersions were found to hold more drugs in solution at equilibrium than in the case of systems containing Cremophor RH40. The inclusion of as little as 10-20% PEG in the lipid mixture accelerated drug precipitation. Bile salt-lecithin mixed micelles appears to some extent enhance the solubilization capacity of these systems after dispersion

Conclusion: Solvency of emulsions formed by self-emulsifying drug delivery in various emulsification media is a crucial parameter influencing the fate of dissolved drug after the dispersion of the formulations.

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. 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.
4. 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.
5. Pouton CW. Key issues when formulating hydrophobic drugs with lipids. Bulletin Technique Gattefosse; 1999.
6. 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.
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. Crew M. Bioavailability enhancement-analysis of the historical use of solubilization technologies. Drug Dev Delivery 2014. Available from: http://www.drug-dev.com/Main/BackIssues/bioavailabilityenhancement. [Last accessed on 20 Jun 2018]
9. Strickley RG. Currently marketed oral lipid-based dosage forms: drug products and excipients. In: Hauss D. editor. Oral lipid based formulations. 1st ed. New York: Informa Healthcare; 2007.
10. Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 2006;1:D668-72.
11. Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res 2004;21:201–30.
12. Agrawal SGT, Tripathi DK, Alexander A. A review on novel therapeutic strategies for the enhancement of solubility for hydrophobic drugs through lipid and surfactant based self micro emulsifying drug delivery system: a novel approach. Am J Drug Discovery Dev 2012;2:143–83.
13. Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-lidose) and the innovator isotretinoin formulation: a randomized, 4-treatment, crossover study. J Am Acad Derma 2013;69:762-7.
14. Bennett LL, Ingason A. Enzalutamide (Xtandi) for patients with metastatic, resistant prostate cancer. Annals Pharmacol 2014;48:530-7.
15. Fukihara J, Kondoh Y. Nintedanib (OFEV) in the treatment of idiopathic pulmonary fibrosis. J Exp Rev Respir Med 2016;10;1247-54.
16. Sprague SM, Strugnell SA, Bishop CW. Extended-release calcifediol for secondary hyperparathyroidism in stage 3-4 chronic kidney disease. Expert Rev Endocrinol Metab 2017;12:289-301.
17. Hasan NM. Role of medium-chain fatty acids in the emulsification mechanistics of self-micro-emulsifying lipid formulations. Saudi Pharm 2014;22:580-90.
18. Hasan MYN. Self-micro-emulsifying lipid formulations to improve the bioavailability of poorly water-soluble drugs. Ph. D. thesis, University of Bath; 2004.
19. Galia E, Nicolaides E, Horter D, Lobenberg R, Reppas C, Dressman JB. Evaluation of various dissolution media for predicting in vivo performance of class I and class II drugs. Pharm Res 1998;15:698-705.
20. Yalkowsky SH, Flynn G, Amidon G. Solubility of non-electrolytes in polar solvents. J Pharm Sci 1972;61:983-4.
21. Yalkowsky SH, Valvani S, Amidon G. Solubility of non-electrolytes in polar solvents IV: non-polar drugs in mixed solvents. J Pharm Sci 1976;65:1488-93.
22. Solubilization of drugs by cosolvents, Techniques of solubilization of drugs: Edited by Yalkowsky SH, Marcel Dekker. New York; 1981. p. 91-134.
23. Hasan NMY. Effect of a model lipophilic compound on the phase behaviour of hydrophilic self-micro-emulsifying lipid formulations. J Pharm Res 2016;10:647-54.
24. Van HP, Liu X, Fahr A. Drug delivery strategies for poorly water-soluble drugs: the industrial perspective. Expert Opin Drug Delivery 2011;8:1481–500.
25. 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.
26. Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev 2016;50:247-63.
27. Myers RA, Stella VJ. Factors affecting the lymphatic transport of penclomedine (NSC-338720), a lipophilic cytotoxic drug: comparison to DDT and hexachlorobenzene. Int J Pharm 1992;80:51-62.
28. Charman WN, Stella VJ. Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules. Int J Pharm 1986;34:175-8.
29. Porter CJH, Charman WN. In vitro assessment of oral lipid based formulations. Adv Drug Delivery Rev 2001;50:127-47.
30. Dressman JB, Reppas C. In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci 2000;11:73-80.
31. Malik NA. Solubilization and interaction studies of bile salts with surfactants and drugs: a review. Appl Biochem Biotechnol 2016;179:179-201.
32. Naylor LJ, Bakatselou V, Dressman JD. Comparison of the mechanism of dissolution of hydrocortisone in simple and mixed micelle systems. Pharm Res 1993:10:865-70.
33. Hoogevest PV. Review–an update on the use of oral phospholipid excipients. Eur J Pharm Sci 2017;108:1–12.
34. Khadra I, Zhou Z, Dunn C, Wilson CG, Halbert G. Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs. Eur J Pharm Sci 2015;67:65-75.
35. Zhou Z, Dunn C, Khadra I, Wilson CG, Halbert GW. Statistical investigation of simulated fed intestinal media composition on the equilibrium solubility of oral drugs. Eur J Pharm Sci 2017;99:95–104.
36. Shankland W. The equilibrium and structure of lecithin-cholate mixed micelles. Chem Phys Lipids 1970;4:109-30.
37. Magee GA, French J, Gibbon B, Luscombe C. Bile salt/lecithin mixed micelles optimized for the solubilization of a poorly soluble steroid molecule using statistical experimental design. Drug Dev Indus Pharm 2003;29:441-50.
38. Amidon GL, Choe SY, Vieira M, Oh DM. Solubility, intrinsic dissolution and solubilization: influence on absorption. In: Amidon GL, Robinson JR, Williams RL. Eds. Scientific foundations for regulating drug product quality, AAPS Press, Alexandria; 1997. p. 99-113.
39. Mithani SD, Bakatselou V, Tenhoor CN, Dressman JD. Estimation of the increase in solubility as a function of bile salt concentration. Pharm Res 1996;13:163-7.
40. Solomon LJ, Embleton JK, Pouton CW. Solubilization of steroidal compounds by mixed bile salt/lecithin micelles. Eur Symposium: Formulation Poorly-Available Drugs For Oral Administration 1996;2:219-22.
41. Miyazaki S, Yamahira T, Morimota Y, Nadia T. Micellar interaction of indomethacin and phenylbutazone with bile salts. Int J Pharm 1981;8:303-10.
42. Trull AK, Tan KKC, Uttridge J, Bauer R, Alexander G, Jamieson NV. Cyclosporine absorption from microemulsion formulation in liver transplant recipient. Lancet 1993;341:433.
43. Charman WN, Rogge MC, Boddy AW, Barr WH, Berger BM. Absorption of danazol after administration to different sites of the gastrointestinal tract and the relationship to single and double peak phenomena in the plasma profiles. J Clin Pharmacol 1993;33:1207-13.
59 Views | 80 Downloads
How to Cite
Hasan, N. (2019). EFFECT OF PHYSICOCHEMICAL PROPERTIES OF EMULSIONS FORMED BY SELF-EMULSIFYING DRUG DELIVERY SYSTEMS (SEDDS) ON THE SOLUBILIZATION STATE OF DRUG: IN VITRO STUDY. International Journal of Applied Pharmaceutics, 11(1), 61-73. https://doi.org/10.22159/ijap.2019v11i1.28664
Original Article(s)