Abstract
The aim of this work was to investigate the effects of formulation variables on development of carvedilol (CAR) proniosomal gel formulations as potential transdermal delivery systems. Different non-ionic surfactants; polyoxyethylene alkyl ethers, namely Brij 78, Brij 92, and Brij 72; and sorbitan fatty acid esters (Span 60) were evaluated for their applicability in preparation of CAR proniosomal gels. A 23 full factorial design was employed to evaluate individual and combined effects of formulation variables, namely cholesterol content, weight of proniosomes, and amount of CAR added on performance of proniosomes. Prepared proniosomes were evaluated regarding entrapment efficiency (EE%), vesicle size, and microscopic examination. Also, CAR release through cellulose membrane and permeation through hairless mice skin were investigated. Proniosomes prepared with Brij 72 and Span 60 showed better niosome forming ability and higher EE% than those prepared with Brij 78 and Brij 92. Higher EE% was obtained by increasing both weight of proniosomes and amount of CAR added, and decreasing cholesterol content. Release rate through cellulose membrane was inversely affected by weight of proniosomes. In Span 60 proniosomes, on increasing percent of cholesterol, a decrease in release rate was observed. While in Brij 72 proniosomes, an enhancement in release rate was observed on increasing amount of CAR added. Permeation experiments showed that skin permeation was mainly affected by weight of proniosomes and that Span 60 proniosomal gels showed higher permeation enhancing effect than Brij 72. Proniosomal gel could constitute a promising approach for transdermal delivery of CAR.
Similar content being viewed by others
References
Couvreur P, Fattal E, Andremont A. Liposomes and nanoparticles in the treatment of intracellular bacterial infections. Pharm Res. 1991;8:1079–86.
Arunothayanun P, Uchegbu IF, Craig DQ, Turton JA, Florence AT. In vitro/in vivo characterisation of polyhedral niosomes. Int J Pharm. 1999;183:57–61.
Baroli B, Delogu G, Fadda AM, Podda G, Sinico C. Vesicle formation from hexasubstituted cyclophosphazenic derivatives. Int J Pharm. 1999;183:101–7.
Schreier H, Bouwstra J. Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery. J Control Release. 1994;30:1–15.
Fang J-Y, Hong C-T, Chiu W-T, Wang Y-Y. Effect of liposomes and niosomes on skin permeation of enoxacin. Int J Pharm. 2001;219:61–72.
Manconi M, Sinico C, Valenti D, Loy G, Fadda AM. Niosomes as carriers for tretinoin. I. Preparation and properties. Int J Pharm. 2002;234:237–48.
Hu C, Rhodes DG. Proniosomes: a novel drug carrier preparation. Int J Pharm. 2000;206:110–22.
Vora B, Khopade AJ, Jain NK. Proniosome based transdermal delivery of levonorgestrel for effective contraception. J Control Release. 1998;54:149–65.
Fang JY, Yu SY, Wu PC, Huang YB, Tsai YH. In vitro skin permeation of estradiol from various proniosome formulations. Int J Pharm. 2001;215:91–9.
Varshosaz J, Pardakhty A, Baharanchi SM. Sorbitan monopalmitate-based proniosomes for transdermal delivery of chlorpheniramine maleate. Drug Deliv. 2005;12:75–82.
Chakraborty S, Shukla D, Jain A, Mishra B, Singh S. Assessment of solubilization characteristics of different surfactants for carvedilol phosphate as a function of pH. J Colloid Interface Sci. 2009;335:242–9.
Wen X, Tan F, Jing Z, Liu Z. Preparation and study the 1:2 inclusion complex of carvedilol with beta-cyclodextrin. J Pharm Biomed Anal. 2004;34:517–23.
Tanwar YS, Chauhan CS, Sharma A. Development and evaluation of carvedilol transdermal patches. Acta Pharm. 2007;57:151–9.
Ubaidulla U, Reddy MV, Ruckmani K, Ahmad FJ, Khar RK. Transdermal therapeutic system of carvedilol: effect of hydrophilic and hydrophobic matrix on in vitro and in vivo characteristics. AAPS PharmSciTech. 2007;8:2.
El-Kattan A, Asbill CS, Haidar S. Transdermal testing: practical aspects and methods. Pharm Sci Technol Today. 2000;3:426–30.
Naik A, Kalia YN, Guy RH. Transdermal drug delivery: overcoming the skin’s barrier function. Pharm Sci Technol Today. 2000;3:318–26.
Mokhtar M, Sammour OA, Hammad MA, Megrab NA. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm. 2008;361:104–11.
Ibrahim MM, Sammour OA, Hammad MA, Megrab NA. In vitro evaluation of proniosomes as a drug carrier for flurbiprofen. AAPS PharmSciTech. 2008;9:782–90.
Alsarra IA, Bosela AA, Ahmed SM, Mahrous GM. Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur J Pharm Biopharm. 2005;59:485–90.
Azeem A, Jain N, Iqbal Z, Ahmad FJ, Aqil M, Talegaonkar S. Feasibility of proniosomes-based transdermal delivery of frusemide: formulation optimization and pharmacotechnical evaluation. Pharm Dev Technol. 2008;13:155–63.
Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin. Int J Pharm. 2007;328:130–41.
Mura S, Pirot F, Manconi M, Falson F, Fadda AM. Liposomes and niosomes as potential carriers for dermal delivery of minoxidil. J Drug Target. 2007;15:101–8.
Bayindir ZS, Yuksel N. Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery. J Pharm Sci. 2010;99:2049–60.
Manosroi A, Wongtrakul P, Manosroi J, Sakai H, Sugawara F, Yuasa M, et al. Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloids Surf, B. 2003;30:129–38.
Pund S, Joshi A, Vasu K, Nivsarkar M, Shishoo C. Multivariate optimization of formulation and process variables influencing physico-mechanical characteristics of site-specific release isoniazid pellets. Int J Pharm. 2010;388:64–72.
Vishnu YV, Chandrasekhar K, Ramesh G, Rao YM. Development of mucoadhesive patches for buccal administration of carvedilol. Curr Drug Deliv. 2007;4:27–39.
Rowe RC, Sheskey PJ, Owen SC. Handbook of Pharmaceutical Excipients. Sixith edition ed: Pharmaceutical Press and the American Pharmacists Association; 2009
Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm. 1998;172:33–70.
Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci. 1995;58:1–55.
Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm. 2009;377:1–8.
El-Samaligy MS, Afifi NN, Mahmoud EA. Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int J Pharm. 2006;308:140–8.
Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60 and 80) and a sorbitan triester (Span 85). Int J Pharm. 1994;105:1–6.
Vemuri S, Yu C-D, Degroot JS, Roosdorp N. In vitro interaction of sized and unsized liposome vesicles with high density lipo proteins. Drug Dev Ind Pharm. 1990;16:1579–84.
Virtanen JA, Ruonala M, Vauhkonen M, Somerharju P. Lateral organization of liquid-crystalline cholesterol-dimyristoylphosphatidylcholine bilayers. Evidence for domains with hexagonal and centered rectangular cholesterol superlattices. Biochemistry. 1995;34:11568–81.
Park ES, Chang SY, Hahn M, Chi SC. Enhancing effect of polyoxyethylene alkyl ethers on the skin permeation of ibuprofen. Int J Pharm. 2000;209:109–19.
Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14:101–14.
Ogiso T, Niinaka N, Iwaki M. Mechanism for enhancement effect of lipid disperse system on percutaneous absorption. J Pharm Sci. 1996;85:57–64.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aboelwafa, A.A., El-Setouhy, D.A. & Elmeshad, A.N. Comparative Study on the Effects of Some Polyoxyethylene Alkyl Ether and Sorbitan Fatty Acid Ester Surfactants on the Performance of Transdermal Carvedilol Proniosomal Gel Using Experimental Design. AAPS PharmSciTech 11, 1591–1602 (2010). https://doi.org/10.1208/s12249-010-9539-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-010-9539-0