In vitro transdermal delivery of propranolol hydrochloride through rat skin from various niosomal formulations


1 Nanotechnology research center, Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Pharmaceutics, School of Pharmacy, Jundishapur University of Medical Sciences, Ahvaz, Iran


The purpose of the present study was to prepare and to evaluate a novel niosome as transdermal drug delivery system for propranolol hydrochloride and to compare the in vitro efficiency of niosome by either thin film hydration or hand shaking method.
Materials and Methods:
Niosomes were prepared by Thin Film Hydration (TFH) or Hand Shaking (HS) method. Propranolol niosomes were prepared using different surfactants (span20, 80) ratios and a constant cholesterol concentration. In vitro characterization of niosomes included microscopical observation, size distribution, laser light scattering evaluation, stability of propranolol niosomes and permeability of formulations in phosphate buffer (pH=7) through rat abdominal skin.
The percentage of entrapment efficiency (%EE) increased with increase in surfactant concentration in all formulations. Among them, F3 formulation (containing span80:cholesterol ratio of 3:1) showed the highest entrapment efficiency (86.74±2.01%), Jss (6.33μg/cm2.h) and permeability coefficient (7.02×10-3cm/h). By increasing the percentage of entrapment efficiency (resulting in increase in surfactant concentration), the drug released time is not prolonged. Among all the formulations, F4 needed more time for maximum drug release. Among these formulations, F4 was also found to have the maximum vesicle size as compared to other formulations. It was observed that niosomal suspension prepared from span 80 was more stable than span 20.
This study demonstrates that niosomal formulations may offer a promise transdermal delivery of propranolol which improves drug efficiency and can be used for controlled delivery of propranolol.

1. Midha K K, Roscoe R M, Wilson W, Cooper J K. Biopharm. Drug Dispos. 1983; 4: 331-338.
2. Walle T, Fagan T, Conrad E, Walle U K, Gafney T. Clin. Pharmacol. Ther. 1976; 26: 167-172.
3. Routlage P A, Shand D G. Clin. Pharmacokintic. 1979; 4:73-90.
4. Blazek-Welsh. A I, Rhodes D G. Maltodextrin-based proniosomes, AAPS Pharm.Sci.2001;3: E1.
5. Arunothayanun .P,Turton .J.A, Uchegbu .I.F, Florence .A.T, Preparation and in vitro in vivo evaluation of luteinizing hormone releasing hormone (LHRH)-loaded polyhedral and spherical tubular niosomes, J. Pharm. Sci. 1999; 88: 34-38.
6. Uchegbu .I.F, Double .J.A, Turton .J.A, Florence .A.T, Distribution, metabolism and tumoricidal activity of doxorubicin administered in sorbitanmonostearate (Span 60) niosomes in the mouse, Pharm. Res.1995;12: 1019.
7. Yoshioka .T, Sternberg .B, Florence .A.T, Preparation and Properties of Vesicles (Niosomes) of Sorbitan Monoesters (Span-20, Span-40, Span-60 and Span-80) and A SorbitanTriester (Span-85).Int. J. Pharm. 1994; 105: 1-6.
8. Lasic .D.D, Liposomes: from physics to application Elsevier, Amsterdam, New York; 1993.
9. Hao .Y, Zhao .F, Li .N, Yang .Y, Li .K, Studies on a high encapsulation of colchicine by aniosome system, Int. J. Pharm. 2002; 244: 73-80.
10. Fang .J.Y, Yu .S.Y, Wu .P.C, Huang .Y.B, Tsai .Y.H, In vitro skin permeation of estradiol from various proniosome formulations, Int. J. Pharm. 2001; 215: 91- 99.
11. Manconi .M, Sinico .C, Valenti .D, Loy .G, Fadda .G.A.M, Niosomes as carriers for tretinoin.I. preparation and properties, Int. J. Pharm. 2002; 234:237–248.
12. Manconi .M, Valenti .D, Sinico .Lai .C.F, Fadda .G.A.M, Niosomes as carriers for tretinoin II.Influence of vesicular incorporation on tretinoinphotostability, Int. J. Pharm.2003; 260: 261–272.
13. Touitou .E, Junginger .H.E, Weiner .N.D, Nagai .T, Mezei .M, Liposomes as carriers for topical and transdermal delivery, J. Pharm. Sci. 1994; 83: 1189–1203.
14. Agarwal .R, Katare .O.P, Vyas .S.P, Preparation and in vitro evaluation of liposomal/niosomal delivery systems forcantipsoriatic drug dithranol, Int. J. Pharm. 2001; 228: 43–52.
15. Fang .J.Y, Hong .C.T, Chiu .W.T, Wang .T.T, Effect of liposomes and niosomes on skin permeation of enoxacin, Int. J. Pharm. 2001; 219: 61–72.
16. Udupa .N, Chandraprakash .K.S, Umadevi .P, Pillai .G.K, Formulation and evaluation of methotrexate niosomes, Drug Develop.Ind. Pharm.1993; 19: 1331–1342.
17. Parthasarathi .G, Udupa .N, Umadevi .P, Pillai .G.K, Niosome-encapsulated vincristine sulfate: improved anticancer activity with reduced toxicity in mice, J. Drug Targ. 1994; 2: 173–182.
18. Jain .C.P, Vyas .S.P, Preparation and characterization of niosomes containing rifampicin for lung targeting, J. Microenc: 1995; 12:401–407.
19. Williams .D.M, Carter .K.C, Baillie .A.J, Visceralleishmaniasis in the BALB/c mouse: a comparison of the in vivo activity of five nonionic surfactant vesicle preparations of sodium stibogluconate, J. Drug Targ.1995; 3: 1–7.
20. Rentel .C.O, Bouwstra .J.A, Naisbett .B, Junginger .H.E, Niosomes as a novel peroral vaccine delivery system, lnt. J. Pharm. 1999; 186: 161–167.
21. Ruchmani K., Jayakar B., Ghosal S.K. Nonionic surfactant vesicles (niosomeof cytarabine hydrochloride for effective treatment of leukemias:encapsulation, storage, and in vitro Release, Drug Development &IndustrialPharmacy, 2000, 26: 217-222.
22. Small .D.M, Handbook of lipid research: The physical chemistry of lipids, from alkanes to phospholipids, first ed., Plenum Press, New York.1986; 4.
23. Uchegbu .I.F, Vyas .S.P, Non-ionic surfactant based vesicles (niosomes) in drug delivery, Pharmaceutics 2. 1998. p.33-70.
24. Patel .R.P, Niosome: An unique drug delivery system, Pharmainfo. net.2007; 6 (5) :1.
25. Joseph .N.M, Niosomes in Targeted Drug Delivery: Some recent advances, Int. J. Pharm. Sci. Res.2010; 1 (9): 1-8.
26. Chengjlu Hu, David .G Rhodes, Pro niosomes, A novel drug carrier preparation, International Journal of Pharmaceutics.2006; 206: 110-122
27. Nagarsenker MS, Londhe VY, Nadkami GD. Preparation and evaluation of liposomal formulation of tropicamide for ocular delivery , Int. j. pharm.1999;190: 63-71.
28. Balakrishnan P, Shanmugam S, Lee WS, Lee W M, Kim J O, Oh DH, Formulation and in-vitro assessment of minoxidilniosomes for enhanced skin delivery, Int. J. Pharm. 2009; 377: 1-8.
29. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicle (niosomes) in drug delivery, Int. J.Pharm.1998; 172: 33-70.
30. Touitou E, Junginger HE, Weiner ND, Nagai T, Mezei M. Liposomes as carriers for topical and transdermal delivery, j. Pharm. Sci. 1994; 83: 1189-1203.
31. Van H D, Vanrensen A, Devringer T, Junginger H, Bouwstra J. Diffusion of estradiol from nonionic surfactant vesicles through human stratum corneum in-vitro, STP Pharm. Sci. 1996; 06:72-78.
32. Bisby R.H., Mead C., Morgan C.H. Photosensitive liposomes as “cages” for laser-triggered solute delivery: the effect of bilayer cholesterol onKinetics of solute release. FEBS Letter, 1999, 463:165-168.
33. Jigar V, Puja V, Krutika S.Formulation and evaluation of topical niosomal gel of erythromici 2011; 3:123-126.
34. Barry BW. Mode of action of penetration enhancers in human skin, J Control Release.1987; 6: 85-97.