FORMULATION AND EVALUATION OF GEL CONTAINING ETHOSOMES ENTRAPPED WITH TRETINOIN
A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of ethosomes which can be transported through the skin through channel-like structures. Tretinoin is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Drug loaded ethosomes had been prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, In-vitro skin permeation, skin retention, drug‐membrane component interaction and stability. The ethosomal formulation having 0.5 %w/v of phospholipid and 20 %v/v of ethanol (F2) showing the greatest entrapment efficiency (80.25±0.23) with small particle size (205.40±2.31nm) was selected for further skin permeation studies. The skin permeation and skin retention studies were performed on ethosomal formulation, liposomal formulation (0.5 %w/v of phospholipid without alcohol), hydroethanolic drug solution and phosphate buffer saline (pH7.4) drug solution. Among them, ethosomal formulation showed higher cumulative percentage of drug permeation (93.36±0.45%) and 8 hours than the other formulations. Scanning electron microscopy confirmed the three dimensional nature of ethosomes. Dynamic light scattering technique proved that the ethosomes has smaller vesicular size than the liposomes prepared without alcohol. FT‐IR studies revealed no interaction between the drug and membrane components. The ethosomal vesicles were incorporated in carbopol gel base and its anti‐acne was compared with the marketed gel. Our results suggest that the ethosomes are an efficient carrier for dermal and transdermal delivery of tretinoin.
Keywords: Tretinoin, Ethosomes, Diffusion, Carbopol gels, Transdermal delivery.
2. Kumar GS, Jayaveera KN, Kumar A, Umachigi P, Vrushabendra BMS, Kumar DVK. Antimicrobial effects of Indian medicinal plants against acne-inducing bacteria. Tropical Journal of Pharmaceutical Research. 2007; 6(2):717–723.
3. Shalita AR, Lee WL. Inflammatory acne. Dermatologic Clinics. 1983; 1:361–364.
4. Gollnick HP, Krautheim A. Topical treatment in acne: current status and future aspects. Dermatology. 2003; 206:29–36.
5. Zaenglein AL. Topical retinoids in the treatment of acne vulgaris. Semin Cutan Med Surg. 2008; 27:177– 182.
6. Tucker R, Walton S. The role of benzoyl peroxide in management of acne vulgaris. Pharm J. 2007; 279:48–53.
7. Spellman MC, Pincus SH. Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne. Clin Ther. 1998; 20:4:711–721.
8. Unkles SE, Gemmell CG. Effect of clindamycin, erythromycin, lincomycin, and tetracycline on growth and extracellular lipase production by propionibacteria in vitro. Antimicrob Agents Chemother. 1982; 21(1):39–43.
9. Toyoda M, Morohashi M. An overview of topical antibiotics for acne treatment. Dermatology. 1998; 196:130–134.
10. Mills OH, Klingman AM. Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Derm Venereol. 1978; 58:555–557.
11. Honeywell-Nguyen PL, Bouwstra JA. Vesicles as a tool for transdermal and dermal delivery. Drug Discov Today Technol. 2005; 2(1):67–74.A
12. Escobar-Chávez JJ, Díaz-Torres R, Rodríguez-Cruz IM, et al. Nanocarriers for transdermal drug delivery. Research and Reports in Transdermal Drug Delivery. 2012; 1:3–17.
13. Braun-Falco O, Kortung HC, Maibach HI, (Eds.), Gries-bach Conference: Liposome Dermatics, Springer-Verlag, Ber-lin, Heidelberg, 1992.
14. E. Touitou H.E. Junginger N.D. Weiner M. Mezei Lipo-somes as carriers for topical and transdermal delivery, J. Pharm. Sci. 1992; 9:1189–1203.
15. Cevc G, Gebauer D, Stieber J, Schatzlein A, Blume G, Ultraflexible vesicles, transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin, Biochim. Biophys. Acta 1998; 1368:201–215.
16. Berner B, Liu P, Alcohols, in: E.W. Smith, H.I. Maibach (Eds.), Percutaneous Penetration Enhancers, CRC Press, Boca Raton, Fl, 1995, pp. 45–60.
17. Touitou E, Compositions for applying active substances to or through the skin, US patent 5,540,934, 1996.
18. Touitou E, Composition for applying active substances to or through the skin, US patent 5,716,638, 1998.
19. Touitou E, Alkabes M, Dayan N, Eliaz M, Ethosomes: novel vesicular carriers for enhanced skin delivery, Pharm. Res. 1997; 14:S305–S306.
20. Touitou E, Dayan N, Levi-Schaffer F, A. Piliponsky, Novel lipid vesicular system for enhanced delivery, J. Lip. Res. 1998; 8:113–114.
21. Valjakka-Koskela R, Kirjavainen V, Monkkonen J, Urtti A, Kiesvaara J, Enhancement of percutaneous absorption of naproxen by phospholipids, Int. J. Pharm. 1998; 175:225–230.
22. Kirjavainen M, Urtti A, Valjakka-Koskela R, Kiesvaara J, Monkkonen J, Liposome–skin interactions and their effects on the skin permeation of drugs, Eur. J. Pharm. Sci. 1999; 7:279–286.
23.Tauitou E., Dayan M., Bergelson L., Godin B., and Eliaz M., J. Controlled Release, 2000; 65:403- 413.
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