Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free flowing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in softgels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen different softgel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.
1. R. K. Maheshwari, A. K. Singh, J. Gaddipati and R. C. Srimal, Multiple biological activities of curcumin: a short review, Life Sci.78 (2006) 2081–2087; DOI: 10.1016/j.lfs.2005.12.007.
2. R. Sharma, C. Ireson, R. Verschoyle, K. Hill, M. Williams, C. Leuratti, M. Manson, L. Marnett and W. Steward, Effects of dietary curcumin on glutathione-S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels, Clin. Cancer Res.7 (2001) 1452–1458.
3. R. A. Sharma, S. A. Euden, S. L. Platton, D. N. Cooke, A. Shafayat, H. R. Hewitt, T. H. Marczylo, B. Morgan and D. Hemingway, Phase I clinical trial of oral curcumin: Biomarkers of systemic activity and compliance, Clin. Cancer Res.10 (2004) 6847–6854.
4. A. Paradkar, A. A. Ambike, B. K. Jadhav and K. R. Mahadik, Characterization of curcumin-PVP solid dispersion obtained by spray drying, Int. J. Pharm.271 (2004) 281–286; DOI: 10.1016/j.ijpharm.2003.11.014.
5. M. H. Leung, H. Colangelo and T. W. Kee, Encapsulation of curcumin in cationic micelles suppresses alkaline hydrolysis, Langmuir.24 (2008) 5672–5675; DOI: 10.1021/la800780w.
6. T. H. Kim, H. H. Jiang, Y. S. Youn, C. W. Park, K. K. Tak, S. Lee, H. Kim and S. Y. Jon, Preparation and characterization of water-soluble albumin bound curcumin nanoparticles with improved antitumor activity, Int. J. Pharm.403 (2011) 285–591; DOI: 10.1016/j.ijpharm.2010.10.041.
7. Y. B. Pawar, H. Purohit, G. Valicherla, B. Munjal, S. V. Lale, S. Patel and A. K. Bansal, Novel lipid based oral formulation of curcumin: development and optimization by design of experiments approach, Int. J. Pharm.436 (2012) 617–623; DOI: 10.1016/j.ijpharm.2012.07.031.
8. J. Cui, B. Yu, Y. Zhao, W. Zhu, H. Li and H. Lou, Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems, Int. J. Pharm.371 (2009) 148–155; DOI: 10.1016/j.ijpharm.2008.12.009.
9. C. G. Chen, T. D. Johnston, H. Jeon, R. Gedaly, P. P. McHugh, T. G. Burke and D. Ranjan, An in vitro study of liposomal curcumin: stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B cells, Int. J. Pharm.366 (2009) 133–139; DOI: 10.1016/j.ijpharm.2008.09.009.
10. K. Maiti, K. Mukherjee, A. Gantait, B. Saha and P. K. Mukherjee, Curcumin-phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats, Int. J. Pharm.330 (2007) 155–163; DOI: 10.1016/j.ijpharm.
11. N. K. Gupta and V. K. Dixit, Bioavailability enhancement of curcumin by complexation with phosphatidylcholine, J. Pharm. Sci.100 (2011) 1987–1995; DOI: 10.1002/jps.22393.
12. J. Zhang, Q. Tang, X. Xu and N. Li, Development and evaluation of a novel phytosome-loaded chitosan microsphere system for curcumin delivery, Int. J. Pharm.448 (2013) 168–174; DOI: 10.1016/j.ijpharm.2013.03.021.
13. P. Shivanand and P. Kinjal, Phytosomes: Technical revolution in phytomedicine, Int. J. PharmaTechRes.2 (2010) 627–631.
14. J. Patel, R. Patel, K. Khambholja and N. Patel, An overview of phytosomes as an advanced herbal drug delivery system, Asian J. Pharm. Sci.4 (2009) 363–371.
15. A. Semalty, M. Semalty, B. S. Rawat, D. Singh and M. S. Rawat, Pharmacosomes: the lipid-based new drug delivery system, Expert Opin. Drug Deliv.6 (2009) 599–612; DOI: 10.1517/17425240902967607.
17. H. I. Benza and W. L. Munyendo, A review of progress and challenges in soft gelatin capsules formulations for oral administration, Int. J. Pharm. Sci. Rev. Res.10 (2011) 20–24.
18. R. P. Gullapalli, Soft gelatin capsules (softgels), J. Pharm. Sci.99 (2010) 4109–4121; DOI: 10.1002/jps.22151.
19. W. J. Jones, Softgels: consumer perceptions and market impact relative to other oral dosage forms, Adv. Ther.17 (2000) 213–221.
20. L. L. Schramm, Emulsions, Foams, and Suspensions: Fundamentals and Applications, Wiley, Weinheim 2005.
21. M. Brewster, R. Vandecruys, J. Peeters, P. Neeskens and G. Verreck, Comparative interaction of 2-hydroxypropyl cyclodextrin and sulfobutylether-cyclodextrin with itraconazole: phase-solubility behavior and stabilization of supersaturated drug solutions, Eur. J. Pharm. Sci.34 (2008) 94–103; DOI: 10.1016/j.ejps.2008.02.007.
22. M. S. Freag, Y. S. Elnaggar and O. Y. Abdallah, Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation, Int. J. Nanomed.8 (2013) 2385–2397; DOI: 10.2147/IJN.S45231.
23. F. Zhang, G. Y. Koh, D. P. Jeansonne, J. Hollingsworth, P. S. Russo, G. Vicente, R. W. Stout and Z. Liu, A novel solubility-enhanced curcumin formulation showing stability and maintenance of anticancer activity, J. Pharm. Sci.100 (2011) 2778–89; DOI: 10.1002/jps.22512.
24. Soybean Phospholipids, in Recent Trends for Enhancing the Diversity and Quality of Soybean (Ed. D. Krezhova), InTech 2011, pp. 483–450.
25. Z. Hou, Y. Li, Y. Huang, C. Zhou, J. Lin, Y. Wang, F. Cui, S. Zhou, M. Jia, S. Ye and Q. Zhang, Phytosomes loaded with mitomycin C-soybean phosphatidylcholine complex developed for drug delivery, Mol. Pharm.10 (2013) 90–101; DOI: 10.1021/mp300489p.
26. M. A. Elsheikh, Y. S. Elnaggar, E. Y. Gohar and O. Y. Abdallah, Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal, Int. J. Nanomed.7 (2012) 3787–3802; DOI: 10.2147/IJN.S33186.
27. X. Ren, X. Mao, L. Si, L. Cao and H. Xiong, Pharmaceutical excipients inhibit cytochrome P450 activity in cell free systems and after systemic administration, Eur. J. Pharm. Biopharm.70 (2008) 279–288; DOI: 10.1016/j.ejpb.2008.03.019.
28. X. Ren, X. Mao, L. Si, L. Cao and J. Qiu, Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo, Eur. J. Pharm. Biopharm.36 (2009) 401–411; DOI: 10.1016/j.ejps.2008.11.002.
29. B. Wahlang, Y. B. Pawar and A. K. Bansal, Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model, Eur. J. Pharm. Biopharm.77 (2011) 275–282; DOI: 10.1016/j.ejpb.2010.12.006.
30. S. A. Saraf, Applications of novel drug delivery system for herbal formulations, Fitoterapia81 (2010) 680–689; DOI: 10.1016/j.fitote.2010.05.001.