Strategies to enhance oral delivery of curcumin using solid self-emulsifying drug delivery systems

Suchiwa Pan-On Duy Toan Pham Waree Tiyaboonchai   

Open Access   

Published:  Jun 14, 2024

DOI: 10.7324/JAPS.2024.168338

Curcumin is a phenolic compound of turmeric with remarkable pharmacological properties. However, curcumin’s inherent poor water solubility, permeability, and instability in the gastrointestinal tract hinder its therapeutic use. Herein, curcumin-loaded solid self-micro- and nanoemulsifying drug delivery systems (C-SSMEDDS and C-SSNEDDS) were developed using Neusilin®UFL2 as a solid carrier. All developed formulations significantly showed improvement in curcumin water solubility, >100-fold as compared to the free curcumin. In both the simulated stomach (pH 1.2) and intestinal (pH 6.8) conditions, C-SSMEDDS and C-SSNEDDS enhanced the dissolution profiles of curcumin with 60%–70% release within 5 minutes and possessed an average droplet diameter of ~100 and ~150 nm, correspondingly. Moreover, permeation studies in the Caco-2 cell monolayer revealed that both formulations provided significantly greater cellular accumulation and absorption compared with the free curcumin. Finally, the C-SSMEDDS and C-SSNEDDS were physicochemically stable for at least 1 year at ambient temperature (25°C ± 0.5°C). In summary, the findings indicated that C-SSMEDDS and C-SSNEDDS are potential strategies for improving curcumin oral bioavailability.

Keyword:     Absorption curcumin dissolution self-emulsifying drug delivery system oral administration


Pan-On S, Pham DT, Tiyaboonchai W. Strategies to enhance oral delivery of curcumin using solid self-emulsifying drug delivery systems. J Appl Pharm Sci. 2024. Online first.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


1. Kotha RR, Luthria DL. Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules. 2019 Aug 13;24(16):2930.

2. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer Res. 2005 Apr;2(2):131-6.

3. Kulkarni S, Dhir A, Akula KK. Potentials of curcumin as an antidepressant. ScientificWorldJournal. 2009 Nov 1;9:1233-41.

4. Xie L, Li XK, Funeshima-Fuji N, Kimura H, Matsumoto Y, Isaka Y, et al. Amelioration of experimental autoimmune encephalomyelitis by curcumin treatment through inhibition of IL-17 production. Int Immunopharmacol. 2009 May;9(5):575-81.

5. Sanmukhani J, Anovadiya A, Tripathi CB. Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study. Acta Pol Pharm. 2011 Sep-Oct;68(5):769-75.

6. Kurien BT, D'Souza A, Scofield RH. Heat-solubilized curry spice curcumin inhibits antibody-antigen interaction in in vitro studies: a possible therapy to alleviate autoimmune disorders. Mol Nutr Food Res. 2010 Aug;54(8):1202-9.

7. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Nov-Dec;4(6):807-18.

8. Tønnesen HH, Karlsen J. Studies on curcumin and curcuminoids. VI. Kinetics of curcumin degradation in aqueous solution. Z Lebensm Unters Forsch. 1985 May;180(5):402-4.

9. Tønnesen HH, Másson M, Loftsson T. Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability. Int J Pharm. 2002 Sep 5;244(1-2):127-35.

10. Sadegh Malvajerd S, Azadi A, Izadi Z, Kurd M, Dara T, Dibaei M, et al. Brain delivery of curcumin using solid lipid nanoparticles and nanostructured lipid carriers: preparation, optimization, and pharmacokinetic evaluation. ACS Chem Neurosci. 2019 Jan 16;10(1):728-9.

11. Karimi N, Ghanbarzadeh B, Hamishehkar H, Mehramuz B, Kafil HS. Antioxidant, antimicrobial and physicochemical properties of turmeric extract-loaded nanostructured lipid carrier (NLC). Colloid Interface Sci Commun. 2018 Jan 1;22:18-24.

12. Ganesan P, Narayanasamy D. Lipid nanoparticles: different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustain Chem Pharm. 2017 Dec 1;6:37-56.

13. Sermkaew N, Ketjinda W, Boonme P, Phadoongsombut N, Wiwattanapatapee R. Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata. Eur J Pharm Sci. 2013 Nov 20;50(3-4):459-66.

14. Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm. 2004 Apr 15;274(1-2):65-73.

15. Zhang P, Liu Y, Feng N, Xu J. Preparation and evaluation of self-microemulsifying drug delivery system of oridonin. Int J Pharm. 2008 May 1;355(1-2):269-76.

16. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004 Apr;58(3):173-82.

17. Chatterjee B, Hamed Almurisi S, Ahmed Mahdi Dukhan A, Mandal UK, Sengupta P. Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view. Drug Deliv. 2016 Nov;23(9):3639-52.

18. Tuleu C, Newton M, Rose J, Euler D, Saklatvala R, Clarke A, et al. Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesterone. J Pharm Sci. 2004 Jun;93(6):1495-502.

19. Franceschinis E, Voinovich D, Grassi M, Perissutti B, Filipovic- Grcic J, Martinac A, et al. Self-emulsifying pellets prepared by wet granulation in high-shear mixer: influence of formulation variables and preliminary study on the in vitro absorption. Int J Pharm. 2005 Mar 3;291(1-2):87-97.

20. Beg S, Jena SS, Patra CN, Rizwan M, Swain S, Sruti J, et al. Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloids Surf B Biointerfaces. 2013 Jan 1;101:414-23.

21. Acharya B, Guru PS, Dash S. Tween-80-n-butanol-diesel-water microemulsion system-a class of alternative diesel fuel. J Dispers Sci Technol. 2014 Oct 3;35(10):1492-501.

22. Bhandari S, Rana V, Tiwary AK. Antimalarial solid self-emulsifying system for oral use: in vitro investigation. Ther Deliv. 2017 Apr;8(4):201-13.

23. Kharat M, Zhang G, McClements DJ. Stability of curcumin in oil-in-water emulsions: impact of emulsifier type and concentration on chemical degradation. Food Res Int. 2018 Sep 1;111:178-86.

24. Sinha Babu SP, Sarkar D, Ghosh NK, Saha A, Sukul NC, Bhattacharya S. Enhancement of membrane damage by saponins isolated from Acacia auriculiformis. Jpn J Pharmacol. 1997 Dec;75(4):451-4.

25. Craig DQ, Barker SA, Banning D, Booth SW. An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy. Int J Pharm. 1995 Jan 31;114(1):103-10.

26. Constantinides PP, Lancaster CM, Marcello J, Chiossone DC, Orner D, Hidalgo I, et al. Enhanced intestinal absorption of an RGD peptide from water-in-oil microemulsions of different composition and particle size. J Controlled Release. 1995 May 1;34(2):109-16.

27. Gupta MK, Vanwert A, Bogner RH. Formation of physically stable amorphous drugs by milling with Neusilin. J Pharm Sci. 2003 Mar 1;92(3):536-51.

28. Fuji Chemical Industries. Neusilin®. [cited 2020 Apr 28]. Available from:

29. Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, et al. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997 Aug 1;15(12):1867-76.

30. Artursson P, Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem Biophys Res Commun. 1991 Mar 29;175(3):880-5.

31. Yee S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man-fact or myth. Pharm Res. 1997 Jun;14(6):763-6.

32. Maher S, Heade J, McCartney F, Waters S, Bleiel SB, Brayden DJ. Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae. Int J Pharm. 2018 Mar 25;539(1-2):11- 22.

33. Srinivasan B, Kolli AR, Esch MB, Abaci HE, Shuler ML, Hickman JJ. TEER measurement techniques for in vitro barrier model systems. J Lab Autom. 2015 Apr;20(2):107-26.

34. Dahan A, Lennernäs H, Amidon GL. The fraction dose absorbed, in humans, and high jejunal human permeability relationship. Mol Pharm. 2012 Jun 4;9(6):1847-51.

35. Mehnert W, Mäder K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001 Apr 25;47(2-3):165-96.

36. Aji Alex MR, Chacko AJ, Jose S, Souto EB. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur J Pharm Sci. 2011 Jan 18;42(1-2):11-8.

Article Metrics
86 Views 11 Downloads 97 Total



Related Search

By author names