RECENT ADVANCEMENT, TECHNOLOGY & APPLICATIONS OF MULTIPLE EMULSIONS
Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophilic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.
2. A.T. Florence and D. Whitehill, Int. J. Pharm.,1982, 11, 277.
3. A.T. Florence and D. Whitehill, J. Colloid Interface Sci., 1981, 79, 243.
4. Sinha V.R., Kumar A., â€Ÿ Multiple Emulsions: An overview of Formulation, Characterization, Stability & Applicationsâ€, Indian J. of Pharm. Sci., 2002, 64(3): 191-199.
5. Vyas S.P., Khar R.K., â€Ÿ Targeted & Controlled Drug Delivery- Novel Carrier Systemsâ€, CBS Publishers, First edition reprint, 2004, ISBN: 81-239-0799-0, Page No.-303-330.
6. Rajesh Kumar, Murugesan S, K., Nanjaian M., â€Ÿ Multiple Emulsion: A Reviewâ€, Int. J. of Recent Advanced in Pharm. Research, 2012, 2(1): 9-19
7. Prajapati SB et. al. An overview of Preparation, Evaluation and Applications of Multiple Emulsionsâ€, International Journal for Pharmaceutical Research Scholars (IJPRS), V-2, I-1, 2013
8. Davis SS, Walker IM. Measurement of the yield of multiple emulsion droplets by a fluorescent tracer technique. Int J Pharm. 1983; 17:203-213.
9. Khan AY. Potentials of Liquid Membrane System:An overview, Pharmainfo.net. 2007;5: Issue 6.
10. Davis SS,Walker IM. Multiple Emulsions as Targetable Delivery Systems. Methods in enzymology. 1987; 149:51-64.
11. Vasiljevic D, Parojcic J, Primorac M, Vuleta G. An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier, Int J Pharm. 2006; 309:171â€“177.
12. Nissim Garti,â€Ÿ Double Emulsions- Scope, limitation & new achievements,â€ Colloids and Surfaces A: Physicochemical & Engineering Aspects, 1997, 233-246
13. Vladisavljevic G.T., Williams R.A., Recent developments in manufacturing emulsions and particulate products using membranesâ€, Advances in Colloid and Interface Science, 2005, 113, 1-20
14. Talegaonkar S, Vyas SP. Inverse targeting of diclofenac sodium to reticuloendothelial systemrich organs by sphere-in-oil-in-water (s/o/w) multiple emulsions containing poloxamer 40. J Drug Target. 2005; 13(3): 173â€“178.
15. Herbert WJ,Lancet. Multiple emulsions; a new form of mineral-oil antigen adjuvant. Lancet. 1965; 11:771.
16. Rishendra Verma and Jaiswal T.N. Protection, humoral and cell mediated immune responses in calves immunized with multiple emulsion haemorragic septicaemia vaccine. Vaccine. 1997; 15: 1254-1260.
17. Bozkir A, Hayta G. Preparation and evaluation of multiple emulsions water-in-oil-in-water (w/o/w) as delivery system for influenza virus antigens. J Drug target.2004; 12(3): 157-164.
18. Bozkir A, Hayta G, Saka OM. Comparison of biodegradable nanoparticle and multiple emulsion containing influenza virus antigen on the in vivo immune response in rats. Pharmazie 2004; 59(9): 723-725.
19. Chiang CW, Fuller GC, Frankenfeld JW, Rhodes CT. Potential use of liquid membranes for drug overdose treatment: in vitro studies. J Pharm. Sci.1978; 67:63-66.
20. Vaziri A Warburton B.Slow release of chloroquine phosphate from taste masked w/o/w multiple emulsion. J Microencap. 1994; 11(6): 641.
21. Florence AT, Omotosho JA, Whateley TL. In Controlled release of drugs: polymers and aggregated systems, Morton, R. Ed., VCH Publishers,1989; 163-183.
22. Garti N, Aserin A. Double emulsions stabilized by macromolecular surfactant. Adv Colloid Interface Sci.1996; 65:37.
23. Hino T, Kawashima Y, Shimabayashi S. Basic study for stabilization of W/O/W emulsion and its application to transcatheter arterial embolization therapy. Adv Drug Deliv Rev. 2000; 45:27.
24. Garti N. Double emulsionsâ€”scope, limitations and new achievements. Colloid Surf. A. 2000; 123/124:233.
25. Mine Y, Shimizu M, Nakashima T. Preparation and stabilization of simple and multiple emulsions using a microporous glass membrane. Colloid Surf. B.1996; 6:261.
26. Ma GH, Sone H, Omi S. Preparation of uniformsized polystyreneâ€“polyacrylamide composite microspheres from a W/O/W emulsion by membrane emulsification technique and subsequent suspension polymerization, Macromolecules. 2004; 37:2954.
27. Kobayashi I, Lou XF, Mukataka S, Nakajima M. Preparation of monodisperse water-in-oil-inwater emulsions using microfluidization and straight-through microchannel emulsification. J Am Oil Chem Soc. 2005; 82:65.
28. Leal-Calderon, F., Schimitt, V.,Bibette,J..Emulsification. Emulsion Science basic principles, Springer New York, 2007, 5-51.
29. Omotosho JA, Whateley TL, Florence AT.vgb Methotrexate transport from internal phase of multiple w/o/w emulsion. J Microencap.1989; 6:183.
30. Omotosho JA,Law TK,Whateley TL,Florence AT. Release from multiple W/O/W emulsion stabilised by Interfacial complexation. J Pharm. Pharmacol.1986; 38: 865.
31. Baker RW, Lonsdale HK. In controlled release: Mechanism and rates Controlled release of biologically active agent. Tonquary AO,R.E.Eds. Plenum press, New York.1974; 15-40.
32. Kita Y,Matsumoto S,Konezawa D. An attempt at measuring the stability of w/o/w type multiple phase emulsions by analysing the concentration of ions. Nippon Yaguku Kaishi.1978; 11:14.
33. Yazan Y, Seiller M, Puisieux F. Multiple emulsions. Oll.Chim.Farmaceutico.1993; 132:187.
34. Khopade AJ, Jain NK. Fine Multiple Emulsions Bearing 6-Mercaptopurine:In Vitro and In Vivo Antitumor Studies. Drug Delivery.1999; 6:181â€“185.
35. Lin TH, Lin SY, Encapsulation and prolonged release behavior of W/O/W type multiple emulsions, J. Chin. Chem. Soc. 1988, 35, 463â€“470.
36. Okochi H, Nakano M. Preparation and evaluation of W/O/W type emulsions containing vancomycin, Adv Drug Del Rev. 2000; 45:5.