Formulation and in vitro evaluation of ethosomes as vesicular carrier for enhanced topical delivery of isotretinoin
Keywords:
Ethosomes, topical delivery, isotretinoin, N-methyl-2-pyrrolidone, eugenolAbstract
The purpose of the present research was to evaluate the ability of ethosomes for topical delivery of isotretinoin. The ethosomal vesicles were prepared with various concentrations of lecithin and ethanol by using hot method. The ethosomal based isotretinoin gel (GEL-ES) was compared to that of marketed formulations isotretinoin (GEL-MF) by using hydrophobic hydroxyl propyl methyl cellulose as gel base. The physicochemical and stability of ethosomal based isotretinoin and a marketed gel (control) were evaluated for organoleptic properties, drug entrapment, drug content uniformity and in vitro drug release and skin permeation studies. F2 ethosomal vesicles containing 2%w/w lecithin and 30%w/w ethanol was found to have shown the best entrapment percentage (99.21%) and also showed suitable physicochemical characteristics for topical administration. Physical stability studies were also conducted for 45 days at 4ĈC and 25ĈC. GEL-ES and GEL-MF were applied to rat skin and penetration was assessed by Franz diffusion cells. In vitro release studies showed that less than 10% of isotretinoin reached the receptor compartment compared to GEL-MF till 8 h. On comparing F2 and F4 gel formulations, F2 gel has shown better controlled release by in vitro drug release and in vitro skin permeation profile than F4 gel. However, the in vitro skin permeation was increased with the addition of enhancers. From the experimental data, it may be concluded that the ethosomal vesicles and enhancers increased the skin permeation and depot formation of drug in the skin.
References
Andreas Katsambas, Anastasia Papakonstantinou. Acne: Systemic treatment Clinics in Dermatology, 2004; 22 (5): 412-418.
Queille-Roussel C, Poncet M, Mesaros S, Clucas A, Baker M, Soloff AM. Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel. Clin Ther. 2001; 23(2):205-12.
Zouboulis ChC: Retinoids – which dermatological indications will benefit in the near future? Skin Pharmacol Appl Skin Physiol. 2001c; 14:303-315.
Amichai B, Grunwlad MH: Isotretinoin in dermatology. J Dermatol Treat 2000; 11:219-240.
Krautheim A, Gollnick P.M. Acne: Topical Treatment Clinics in Dermatology. 2004; 22:398-407.
Merdan VM, Alhaique F, and Touitou E. Vesicular carriers for topical delivery. Acta Tachno. Legis Medicament. 1998; 12: 1-6.
Touitou, E. Composition of applying active substance to or through the skin. US patent, 5,716,638, 1996.
Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M, Ethosomes-novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J. Control. Release, 2000; 65:403-418.
Jain H, Patel J, Joshi K, Patel P, Upadhyay UM. Ethosome: A novel drug carrier. Pharmacie Globale (IJCP). 2011; 7(01).
Barry BW. Dermatological formulation: percutaneous absorption. Marcel Dekker, New York, 1983.
Akiladevi D, Basak D. Ethosomes: A non-Invasive approach for transdermal drug delivery. Int. J. Curr. Pharm. Res, 2010; 2(4, 14): 1-4.
Sheer A, Chauhan M. Ethosomes as vesicular carrier for enhanced transdermal delivery of ketoconazole- formulation and evaluation. IJPI’s Journal of Pharmaceutics and Cosmetology. 2011; 1(3): 1-14.
Waghmare N, Waghmare P, Wani S, Yerawar A. Development of isotretinoin gel for treatment of acne vulgaris. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2011; 2(1): 220-230.
Kumar V, M.R, Abdul Hasan Sathali A, Arun K. Formulation and evaluation of diclofenac potassium ethosomes. International Journal of Pharmacy and Pharmaceutical Sciences. 2010; 2(4): 82-86.
Touitou E, Alkabes M, Dayan N. Ethosomes : Novel lipid vesicular system for enhanced delivery. Pharm. Res. 1997; 14: 305-306.
Navjot Kaur,1 Richa Puri,1 and Subheet Kumar Jain, Drug-Cyclodextrin-Vesicles Dual Carrier Approach for Skin Targeting of Anti-acne Agent. AAPS PharmSciTech 2010; 11 (2): 528-537.
Tashtoush BM, Jacobson EL, Jacobson MK. A rapid HPLC method for simultaneous determination of tretinoin and isotretinoin in dermatological formulations. J Pharm Biomed Anal. 2007; 43 : 859-64
Godin B, Touitou E. Ethosomes: new prospects in transdermal delivery. Crit Rev Ther Drug Carrier Syst. 2003; 20(1):63-102.
Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate:
In vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release 2005; 106:99-110.
Nava D, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomater 2000; 21:1879-1885.
Liu X, Liu H, Liu J, He Z, Ding C, Huang G, Zhou W, Zhou L. Preparation of a ligustrazine ethosome patch and its evaluation in vitro and in vivo. Int J Nanomedicine 2011; 6:241-247.
Dayan, N and Touitou. Carrier for skin delivery of trihexyphenidyl HCl: Ethosomes vs.liposomes.E. Biomaterials 2000; 21:1879-1885.
Cevc G, Blume G, Schatzlein A. Transfersomes mediated transepidermal delivery improves the regiospecificity and biological activity of corticosteroids in vivo. J Control Release. 1997; 45:211–26.
Rajan Rajabalaya, Sheba Rani Nakka David, Jasmina Khanam, Arunabha Nanada. Studies on the effect of plasticizer on in vitro release and ex vivo permeation from Eudragit E 100 based chlorpheniramine maleate matrix type transdermal delivery system. Journal of Excipients and Food Chemicals, 1 (2) 3-12, 2010.
