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RECENT ADVANCES IN “RECENT ADVANCES IN COSMECEUTICALS ” MICROEMULSION By Rohini P. Wankhade Guide: Dr. (Mrs.) S. S. Bhalerao Dr. L. H. Hiranandani College of Pharmacy


COSMECEUTICALS Cosmeceuticals represent the marriage of cosmetics and pharmaceuticals .


COSMETICS PHARMACEUTICS According to the FDC Act, drug is defined as an article intended for use in the diagnosis, mitigation , treatment, or prevention of disease or intended for use in the diagnosis, mitigation, treatment or prevention of disease or intended to affect the structure or any function of the body. According to the FDC act of 1938, a cosmetic is defined as an article intended to be rubbed , poured, sprinkled, or sprayed on, introduced into , or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance without affecting structure or function.

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A cosmeceutical is a product with medicinal properties that manifests beneficial topical actions and provides protection against degenerative skin. The word “ cosmeceutical ” was coined by dermatologist Albert M. Kligman , The term encompasses cosmetic actives with therapeutic , disease fighting, or healing properties. Serving as a bridge between personal care products and pharmaceuticals


Cosmeceuticals means : The product has pharmaceutical activity and can be used on normal or near normal skin. The product should have a defined benefit for minor skin disorders and cosmetic indication. As the skin disorder is mild, the product should have a very low-risk profile


NOVEL COSMECEUTICAL DELIVERY SYSTEM There have been a lot of advances in cosmeceuticals due to the competitive market and a lot of attention is being directed towards more sophisticated dispersed system, such as liposomes and microemulsion , instead of the traditional creams, ointments and emulsions. The more sophisticated forms of emulsion such as microemulsion , multiple emulsions, have been developed to improve appearance, stability, ease of application and to allow for controlled or sustained release of the active agent. The mode of application to the skin remains the same. However, there have been a lot of advances in cosmeceutical delivery system which leads to an increase in efficiency.

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WHY MICROEMULSION The cosmeceutical industry is constantly seeking new and pioneering products that will combine both proven biological activity and an efficient delivery system. Microemulsions have emerged as prospective delivery system .

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Types of Microemulsion

Key difference between micro and macro emulsion:

Key difference between micro and macro emulsion S. No Properties Microemulsion Emulsion 1 Appearance Transparent (or translucent) Cloudy 2 Interfacial tension Ultra low High 3 Optical isotropy Isotropic Anisotropic 4 Droplet size 10 to 200nm >1000 nm 5 Stability Thermodynamically stable Thermodynamically unstable 6 Phases Monophasic Biphasic 7 Preparation Relatively lower cost for commercial production Require a large input of energy, higher cost 8 Viscosity Low viscosity with Newtonian behavior Higher viscosity 9 Schematic representation



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Raw Material Origin Examples Oils Natural Olive oil, soybean oil, corn oil, coconut oil, castor oil, jojoba oil Synthetic Isopropyl myristate , isopropyl palmitate , ethyl laurate , oleic acid, cetyl behenate Surfactants Natural Lecithin, sugar surfactants such as alkyl glucosides and alkyl esters Synthetic Anionic: Sodium dodecyl sulfate, sodium laureth sulfate Nonionic: Tweens , Spans, Poloxamers , Bryj , cetyl alcohol, cocamide MEA Cationic: Quarternary ammonium alkyl salts e.g. cetyl trimethyl ammonium bromide Zwitterionic ( Amphoteric ): Dodecyl betaine , cocamidopropyl betaine Cosurfactants Natural Phosphatidylcholine , phosphatidylethanolamine Synthetic Ethanol, isopropanol , propanol (short chain alcohols), transcutol , polyethylene glycol, propylene glycol , etc.


METHODS OF PREPARATION Microemulsions are prepared by the spontaneous emulsification method (phase titration method) And can be depicted with the help of phase diagrams. Phase inversion of microemulsions occurs upon addition of excess of the dispersed phase or in response to temperature . During phase inversion, drastic physical changes occur including changes in particle size. These methods make use of changing the spontaneous curvature of the surfactant. e.g.polyoxyethylene type surfactant






MOISTURIZERS One of the major advantages of microemulsion technology is its ability to form improved dispersions for some materials. The attempt was used to solve the problem of instability of conventional neem oil emulsions. The microemulsion was primary short chain (C1-C6) alcohol free, ionic cosurfactant -free and stable upon dilution. The invention was advantageous by permitting alcohol free microemulsion formation which is in great demand, particularly in the pharmaceutical industries. Further, nano -sized (1-100 nm) oil droplets formed were expected to enhance the potency of the oil though improved absorption rates. Neem microemulsions were particularly well suited for use as skin care and cure products, and hand lotions.


By use of microemulsion technology it is possible to achieve high concentration of filter substance. EXAMPLE: 4,4’,4”- (1,3,5-triazine-2,4,6-triyltriimino) tris -benzoic acid, tris (2- ethylhexyl ester) , 2-phenylbenzimidazole-5-sulphonic acid SUNSCREEN PREPARATIONS


ANTIACNE PREPARATION Microemulsions of azelaic acid, a bioactive molecule used in many skin disorders, prepared using the monosodium salt (AZA-Na) have been evaluated as delivery vehicles. To increase the solubility of azelaic acid in the dispersed oil phase of microemulsion containing polysorbate , butanol , decanol:dodecanol (2/1) and water, the pH of aqueous phase was lowered and propylene glycol was added. An increased partitioning into the lipophilic phase was noted as propylene glycol concentration was increased. Microemulsion thus provided a vehicle in which azelaic acid was dissolved rather than suspended as in a cream. Moreover, reservoir effect achieved by partitioning into the oil could prolong its release over several hours.


ANTIOXIDANTS This antioxidant serum helps diminish the appearance of fine lines and wrinkles and improves the skin tone and texture. It delivers a steady targeted supply of retinyl palmitate (Vitamin A), Tocopheryl Acetate (Vitamin E), Beta-Carotene And other factors to nourish and enhance the skin whilst protecting against free radical damage. Suitable for normal, dry, mature or environmentally damaged skin types. Key ingredients: Tocopheryl (Vitamin E), Retinyl Palmitate (Vitamin A) and Retinol Agera Microemulsion Antioxidant

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OTHER PREPARATIONS: Skin whitening agent Microemulsion gel –based system of babchi oil The in vitro skin permeation profile of a formulation consisting of 1.67% v/v of babchi oil, 8.33% v/v of oleic acid, 55% v/v of Tween 80: Transcutol -P (1:1) and 35% v/v of distilled water

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CASE STUDIES MICROEMULSION GEL A comparison of in vitro release profiles through hairless skin membrane from microemulsion is shown in the fig. which shows that a pronounced enhancement of penetration is achieved; after 8h about 35% of the azelaic acid present in microemulsion had been transported compared with only 1.8% from the gel Fig. Permeation profiles of azelaic acid from microemulsion and from gel.

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An O/W microemulsion formulated using lecithin and an alkyl glucoside as mild, non – irritating surfactant proposed as vehicle for arbutin and kojik acid, naturally occurring whitening agents. The photostability to UVB irradiation of both whitening agents was determined in aqueous solution and in microemulsion . The stability of arbutin and kojik acid was higher in microemulsion than in aqueous solution. O/W microemulsion of arbutin and kojik acid Photodegradation of 0.25 % w /w arbutin

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Photodegradation of 0.25 % w/w kojik acid

Diameters of Microemulsion after repeated freeze-thaw cycles:

Diameters of Microemulsion after repeated freeze-thaw cycles Microemulsion Mean diameter (nm) Just prepared One week freeze thaw cycles Alone 27.3 25.2 With Arbutin 27.5 25.4 With Kojik acid 25.5 25.7



Dermaxin Anti-wrinkle product:

Dermaxin Anti-wrinkle product Complexion MD Anti-Wrinkle Cream

White Glow Skin Whitening and Brightening Micro-Emulsion :

White Glow Skin Whitening and Brightening Micro-Emulsion

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ACKNOWLEDGEMENTS I am highly indebted to Dr. S.S. Bhalerao for their guidance and constant supervision as well as for providing necessary information regarding the my presentation & also for their support. I have taken efforts in this presentation. However, it would not have been possible without the kind support and help of many individuals and organizations. I would like to extend my sincere thanks to all of them .


REFERENCES Cosmetic product review,2005 Berl jan Veremeer Chapter 2;Drugs vs cosmetics;cosmetic science and Technology series pg:9 11 S.A. Centurion, cosmeceuticals,http // Shlomo Magdassi,Elka Touifou , Novel cosmetic delivery system,cosmetic science and technology series, vol 19. Schott, H.; Colloidal Dispersion In Remington: The science and practice of pharmacy, Twentieth Edition; Ed: Gennaro , A.F.; Lippincott Williams and Wilkins, 2000, Vol-1; 313 – 314. Vyas , S.P., Khar , R.K.; Submicron emulsions in targeted and controlled drug delivery, Novel Carrier Systems; CBS Publishers and Distributors, New Delhi, 2002; 282 – 302. Farah, N., Denis, J.: US20006054136 (2000) . Elena P, Paola S, Maria RG. Transdermal permeation of apomorphine through hairless mouse skin from microemulsions . Int J Pharm 2001; 226: 47-51. Rhee Y-S, Choi J-G, Park E-S, Chi S-C. Transdermal delivery of ketoprofen using microemulsions . Int J Pharm 2001; 228: 161-170 Ghosh PK, Murthy RSR. Microemulsions : A potential drug delivery system. Curr Drug Delivery 2006; 3: 167-180. Tenjarla S. Microemulsions : an overview and pharmaceutical applications. Crit Rev Therapeutic Drug Carrier Syst 1999; 16: 461-521. Lawrence MJ, Rees GD. Microemulsion based media as novel drug delivery systems. Adv Drug Deliv Rev 2000; 47: 89-121 J. Cosmet . Chem.. , 34, 335-350(November 1983) [18] Potts, RO, Francoeur ML. The influence of stratum corneum morphology on water permeability. J Invest Dermatol 1991; 96: 495-499. Jung K, Seifert M, Herrling Th , Fuchs J. UV-generated free radicals (FR) in skin: Their revention by sunscreens and their induction by self-tanning agents. Spectrochim Acta Part A 2008; 69:1423–1428. Linn, E.E., West, M.P.: US4797272 ( 1989 ) Acosta, E., Kurlat , D.H., Bisceglia , M., Ginzberg , B., Baikauskas , L.., Romano, S.D.; Induced electric birefringence and viscosity studies in microemulsions , Colloids Surfaces A: Physicochem . Eng. Aspects, 1996, 106; 11–21.

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Regev , O., Ezrahi , S., Aserin , A., Garti , N., Wachtel , E., Kaler , E.W., Khan, A., Talmon , Y.; A study of the microstructure of a four-component nonionic microemulsion by cryo -TEM, NMR, SAXS and SANS, Langmuir, 1996,12; 668–674. Kahlweit, M., Strey, R., Haase, D., Kunieda, H., Schmeling, T., Faulhaber, B., Borkovec, M., Eicke , H.F., Busse , G., Eggers, F., Funck , T.H., Richmann , H., Magid , L., Soderman , O., Stilbs,P ., Winkler, J., Dittrich , A., Jahn , W.; How to study microemulsions , J. Colloid Interface Sci,1987, 118; 436–453. Bolzinger , M.A., Thevenin , M.A., Grossiord , J.L., Poelman , M.C.; Characterisation of a sucrose ester microemulsion by freeze fracture electron micrograph and small angle neutron scattering experiments, Langmuir , 1999, 15; 2307–2315. Auvray , L., Cotton, J.P., Ober , R., Taupin , C.; Evidence for zero mean curvature microemulsions,J . Phys. Chem., 1984,88; 4586–4589. Jung K,Seifert M, Herrling Th , Fuchs J.UV- generated free radicals(FR) in skin: Their prevention by sunscreen and by self- tanning agents. Spectrochim Acta Part A 2008;69: 1423-1428 Martin, A.; Coarse Dispersions In Physical Pharmacy, Fourth Edition; B.I. Waverly Pvt. Ltd., New Delhi, 1994; 495 – 496. Benner, G., Heptner, A., Knuppel, A.: US20046805871 ( 2004 ) Sushama Talegaonkar,Emerging role of Microemulsion in Cosmetics Recent Patent on Drug Delivery and Formulation ,2008 Serum Antioxidant-Serum.html Niramala Grampurohit , Padmini Ravikumar Microemulsion - for topical use,Indian Journal of pharmaceutical science and research. David Attwood, Chapter 2 , Microemulsion pg no.64 A Jayakrishnana , K. Kalaiarasi , D. O. Shah , Microemulsion:Evolving technology for cosmetic application M. Gallarate , M. E. Carlotti , M.Trotta , A. E. Grande, and C. Larico , Stability of naturally occurring skin whitening agent in microemulsion , April 2004 php

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