DEVELOPMENT AND OPTIMIZATION OF RIZATRIPTAN BENZOATE ETHOSOMES
Objective: The objective of this study was to assess the development of ethosomal drug delivery system for site-specific topical delivery of rizatriptan benzoate (RBZ) for sustained action.
Methods: In the present study ethosomes were prepared using the cold method. The formulation was optimized using 33 full factorial designs. The lipid concentration (X1), ethanol concentration (X2) and stirring speed (X3) were selected as independent factors and the vesicle size (Y1) and % entrapment efficiency (Y2) were selected as dependent variables.
Results: The equation of multiple regression revealed that there was no significant interaction among factors. The lipid concentration had a positive effect on vesicle size while ethanol concentration and stirring speed had a negative effect. For entrapment efficiency, all factors showed a positive effect while lipid concentrative found to be the main influencing factor. The formulation F4E459 (4% SPC, 45% v/v ethanol 900 RPM), which was characterized by optimum vesicle size (5.5 Âµm) and high entrapment efficiency (93.32%), was considered to be an optimal formulation. The scanning electron microscopy (SEM) results showed that RBZ ethosome have a smooth surface. The polydispersity index (PI) and zeta potential of the optimized formulation were found to be 0.493Â±0.021andâ€“21.3 mV respectively. In vitro permeation through rat abdominal skin from the ethosomal gel followed Higuchi diffusion model over a period of 8 h.
Conclusion: The results obtained in this research work clearly indicated a promising potential of ethosomal carrier system of RBZ for migraine treatment with a topical approach for sustained action.
2. Lee Y, Conroy JA, Stepanavage ME, Mendel CM, Somers G, Mcloughlin DA, et al. Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers. Br J Clin Pharmacol 1999;47:373â€“8.
3. Ramadan NM, Buchanan TM. New and future migraine therapy. Pharmacol Ther 2006;112:199â€“212.
4. Fontebasso M. Current treatment options in the management of a migraine. Prescriber 2008;19:42â€“58.
5. Lahoti SR, Taur NG, Khan AR, Puranik PK. Enhanced Iontophoretic permeation of rizatriptan benzoate from the thermo-reversible gel based system: effect of penetration enhancers and pulsed current. Indian J Pharm Educ Res 2012;46:105â€“11.
6. Aung-din R. European patent 1 435 945 b1. 2008;1:1â€“17.
7. Sharma A, Tiwary AK. Elastic liposomal formulation for sustained delivery of antimigraine drug: in vitro characterization and biological evaluation. Drug Dev Ind Pharm 2008;34:1100â€“10.
8. Aung-din R. United States Patent; 2012. p. 2.
9. FemenÃa Font A, Balaguer FernÃ¡ndez C, Merino V, Lopez Castellano A. Iontophoretic transdermal delivery of sumatriptan: effect of current density and ionic strength. J Pharm Sci 2005;94:2183â€“6.
10. Aung Din R. United States Patent; 2012. p. 2.
11. Dubey V, Mishra D, Jain NK. Melatonin loaded ethanolic liposomes: Physicochemical characterization and enhanced transdermal delivery. Eur J Pharm Biopharm 2007;67:398â€“405.
12. 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 Controlled Release 2007;123:148â€“54.
13. Dubey V, Mishra D, Nahar M, Jain V, Jain NK. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes. Nanomed Nanotechnol Biol Med 2010;6:590â€“6.
14. Menon S, Verma D, Khuroo T, Talegaonkar S, Iqbal Z. Extraction of a water soluble bioactive hypoxoside and its development into an ethosomal system for deep dermal delivery. Int J Pharm Pharm Sci 2015;7:211â€“5.
15. Nair R, Kumar KSA, Vishnu K, Badivaddin T, Sevukarajan M. Preparation and characterization of rizatriptan loaded solid lipid nanoparticles. J Biomed Sci Res 2011;3:392â€“6.
16. 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.
17. Touitou E, Godin B, Dayan N, Weiss C, Piliponsky A, Levi-Schaffer F. Intracellular delivery mediated by an ethosomal carrier. Biomaterials 2001;22:3053â€“9.
18. Esposito E, Menegatti E, Cortesi R. Ethosomes and liposomes as topical vehicles for azelaic acid: a preformulation study. J Cosmet Sci 2004;55:253â€“64.
19. Rao Y, Zheng F, Zhang X, Gao J, Liang W. In vitro percutaneous permeation and skin accumulation of finasteride using vesicular ethosomal carriers. AAPS PharmSciTech 2008;9:860â€“5.
20. Li G, Fan Y, Fan C, Li X, Wang X, Li M, et al. Tacrolimus-loaded ethosomes: Physicochemical characterization and in vivo evaluation. Eur J Pharm Biopharm 2012;82:49â€“57.
21. Rao Y, Zheng F, Zhang X, Gao J, Liang W. In vitro percutaneous permeation and skin accumulation of finasteride using vesicular ethosomal carriers. AAPS PharmSciTech 2008;9:860â€“5.
22. Azeem A, Ahmad FJ, Khan ZI, Talegaonkar S, Azeem A, Ahmad FJ, et al. Nonionic surfactant vesicles as a carrier for transdermal delivery of frusemide. J Dispers Sci Technol 2008;29:37â€“41.
23. Pawar AP, Gholap AP, Kuchekar AB, Bothiraja C, Mali AJ. Formulation and evaluation of optimized oxybenzone microsponge gel for topical delivery. J Drug Delivery 2015:1â€“9. http://dx.doi.org/10.1155/2015/261068
24. Mohammed MI, Makky AMA, Abdellatif MM. Formulation and characterization of ethosomes bearing vancomycin hydrochloride for transdermal delivery. Int J Pharm Pharm Sci 2014;6:190â€“4.
25. Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl-ethosomes vs liposomes. Biomaterials 2000;21:1879â€“85.
26. Manconi M, Sinico C, Caddeo C, Vila AO, Valenti D, Fadda AM. Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin. Int J Pharm 2011;412:37â€“46.
27. Li G, Fan C, Li X, Fan Y, Wang X, Li M, et al. Preparation and in vitro evaluation of tacrolimus-loaded ethosomes. Sci World J 2012:1â€“6. http://dx.doi.org/10.1100/2012/874053
28. Verma P, Pathak K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomed Nanotechnol Biol Med 2012;8:489â€“96.
29. Nimisha, Srivastava K, Singh AK. Formulation and evaluation of seabuckthorn leaf extract loaded ethosomal gel. Asian J Pharm Clin Res 2015;8:309â€“12.
30. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modelling on drug release from controlled drug delivery systems. Acta Pol Pharm 2010;67:217â€“23.