TRANSETHOSOMES AND ETHOSOMES FOR ENHANCED TRANSDERMAL DELIVERY OF KETOROLAC TROMETHAMINE: A COMPARATIVE ASSESSMENT
Keywords:Ketorolac tromethamine, Transdermal delivery, Transethosomes, ethosomes, Permeation studies
The aim of this investigation was to formulate, evaluate and compare the transdermal potential of novel vesicular carriers: transethosomes and ethosomes. Transethosomes (TELs) and ethosomes (Els) were prepared by cold method and were characterized for particle size, entrapment efficiency, transmission electron microscopy (TEM), zeta potential, elasticity measurement, in-vitro drug release, ex-vivo permeation studies and in-vivo study. Transethosomal and ethosomal formulation showed particle size of 180 Â± 70 nm and134 Â± 65 nm. Transethosomes showed higher drug entrapment (80.08 Â± 4.5%) than ethosomes (70.79 Â± 5.6%). Both the formulation showed good zeta potential indicating good stability. The elasticity of transethosomal vesicles was found to be 3-fold higher than the ethosomal vesicles. The transdermal flux of transethosomal gel was 47.43Â± 0.2 Âµg/cm2/h and was found to give 3 fold increase in release as compared to ethosomal gel which gave 2 fold higher release of 40.38 Â± 2.50Âµg/cm2/h as compared to the hydroethanolic solution with a release of 17.333Â± 0.15Âµg/cm2/h. Hence, the results suggested transethosomes to be a more efficient carrier system as compared to ethosomes for transdermal delivery of ketorolac tromethamine.
Reinhart DI. Minimizing the Adverse Effects of Ketorolac. Drug Saf 2000;22:487-97.
Thomas BJ, Finnin BC. The Transdermal Revolution. Drug Discov Today 2004;9:697-703.
Cevc G. Lipid vesicles and other colloids as a drug carrier on the skin. Adv Drug Deli Rev 2004;56:675-711.
Cevc G. Transfersomes, Liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst 1996;13:257-388.
El Maghraby GMM, Williams AC, Barry BW. Interactions of Surfactants (Edge Activators) and Skin Penetration Enhancers with Liposomes. Int J Pharm 2004;276:143-61.
Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 2007;332:1-16.
Song CK, Balakrishnan P, Shim C, Chung S, Chong S, Kim D. A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in-vitro/in-vivo evaluation. Colloids Surf B 2012;92:299â€“ 304.
Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes-Novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Controlled Release 2000;65:403â€“18.
Filipe V, Hawe A, Jiskoot W. Critical evaluation of nanoparticle tracking analysis (NTA) by nanosight for the measurement of nanoparticles and protein aggregates. Pharm Res 2010;27:796â€“810.
Jain S, Jain N, Bhadra D, Tiwary AK, Jain NK. Vesicular approach for drug delivery into or across the skin: current status and future prospects. Curr Drug Delivery 2005;2:222-33.
Nayak AK, Mohanty B, Sen KK. Comparative evaluation of invitro diclofenac sodium permeability across excised mouse skin from different common pharmaceutical vehicles. Int J Pharm Tech Res 2010;2:920â€“30.
Prasanthi D, Lakshmi PK. Development of ethosomes with taguchi robust design-based studies for transdermal delivery of alfuzosin hydrochloride. Int Curr Pharm J 2012;1:370-5.
Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied ethosomal. J Nanobiotechnol 2008;6:6-8.
Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J Cont Rel 2007;123:148-54.
Paolino D, Giuseppe L, Domenico M, Franco A, Massimo F. Ethosomes for skin deliveryof ammonium glycyrrhizinate: invitro percutaneous permeation through human skin and invivo antiâ€inflammatory activity on human volunteer. J Control Release 2005;106:99â€“110.
Touitou E, Godin B, Dayan N, Weiss C, Piliponsky A. Intracellur delivery mediated by an ethosomal carrier. Biomater 2001;22:3053-9.
Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessement of minoxidil niosomes for enhanced skin delivery. Int J Pharm 2009;377:1-8.
Hiruta Y, Hattori Y, Kawano K, Obata Y, Maitani Y. Novel ultra-deformable vesicles entrapped with bleomycin and enhanced to penetrate rat skin. J Control Release 2006;113:146-54.
Chen Y, Lu Y, Chen J, Lai J, Sun J, Hu F, et al. Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int J Pharm 2009;376:153â€“60.
Kirjavainen M, Monkkonen J, Saukkosaari M, Valjakka-Koskela R, Kiesvaara J, Urtti A. Phospholipids affect stratum corneum lipid bilayer fluidity and drug partitioning into the bilayers. J Control Release 1999;58:207-14.
Johnson LB, Kauffmann CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis 2003;36:630-7.
Ruhnke M, Schmidt-Westhausen A, Trautmann M. In vitro activities of voriconazole (uk-109,496) against fluconazole-susceptible and resistant candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection. antimicrob. Agents Chemother 1997;41:575-7.
Touitou E, Alkabes M, Dayan N. Ethosomes: novel lipid vesicular system for enhanced delivery. Pharm Res 1997;14:305-6.
Essa EA, Bonner MC, Barry BW. Electroporation and ultradeformable liposomes; human skin barrier repair by phospholipid. J Control Release 2003;92:163-72.
Lin SY, Duan KJ, Lin TC. Microscopic FT-IR/DSC system used to simultaneously investigate the conversion process of protein structure in porcine stratum corneum after pretreatment with skin penetration enhancers. Methods Find Exp Clin Pharmacol 1996;18:175â€“81.
Rong H, Da-xiang C, Feng G. Preparation of fluorescence ethosomes based on quantum dots and their skin scar penetration properties. Mater Lett 2009;63:1662â€“4.
Khurana S, Jain NK, Bedi PMS. Nanoemulsion based gel for transdermal delivery of meloxicam: physico-chemical, mechanistic investigation. Life Sci 2013;92:383-92.
Babua RJ, Pandit JK. Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir type transdermal delivery systems. Int J Pharm 2005;288:324-34.