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Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Oleic Acid Vesicles for Transdermal Delivery of Propranolol Hydrochloride: Development and Characterization

Author(s): Lalit Kumar and Puneet Utreja*

Volume 15, Issue 3, 2020

Page: [238 - 248] Pages: 11

DOI: 10.2174/1574885514666190722164119

Abstract

Background: Pharmaceutical scientists are exploring the transdermal route for the treatment of various systemic diseases nowadays. Transdermal nanocarrier systems show various advantages like bioavailability enhancement of drugs, avoidance of first-pass hepatic metabolism, and reduction of dosing frequency of bioactive therapeutic molecules.

Objective: The objective of the present research work was to encapsulate Propranolol hydrochloride into oleic acid vesicles and carry out in-vitro and in-vivo evaluation of oleic acid vesicular gel containing Propranolol hydrochloride.

Methods: Propranolol hydrochloride loaded oleic acid vesicles were prepared by exploring the thin film hydration method. Developed vesicles were evaluated for morphology, size, zeta potential and Polydispersity Index (PDI). Thermal behavior of drug-loaded vesicles was checked using Differential Scanning Calorimetry (DSC) and depth of skin penetration was determined using Confocal Laser Scanning Microscopy (CLSM). Oleic acid vesicles dispersed in Carbopol 934R gel were subjected to in-vivo evaluation in male Sprague Dawley rats through measurement of plasma concentration and tissue distribution of Propranolol hydrochloride.

Results: Optimized formulation having oleic acid: Propranolol hydrochloride in the ratio 7 : 3 showed highest entrapment (56.1 ± 0.7%), acceptable size (291.3 ± 2.2 nm), the optimum value of PDI (0.219 ± 0.043) and zeta potential (-27.13 ± 0.25 mV). The results of DSC analysis showed effective encapsulation of drug inside the vesicles and CLSM analysis revealed penetration of vesicles up to stratum spinosum layer of skin. The results of in-vivo study revealed capability of vesicular gel to prolong the release of Propranolol hydrochloride up to 24 h with a Cmax value of 83.6 ± 3.0 ng/mL which was higher compared to the marketed tablet of Propranolol hydrochloride [Inderal R (40 mg), Abbott India Ltd.] (45.6 ± 3.1 ng/mL). Tissue distribution studies revealed higher percentage of Propranolol hydrochloride in various organs after 24 h of administration of vesicular gel compared to marketed tablet.

Conclusion: Developed oleic acid vesicular gel could be effective to reduce dosing frequency and avoid side effects of oral Propranolol hydrochloride.

Keywords: Dosing frequency, oleic acid vesicles, propranolol hydrochloride, transdermal, zeta potential, molecule.

Graphical Abstract
[1]
Conjeevaram R, Chaturvedula A, Betageri GV, Sunkara G, Banga AK. Iontophoretic in vivo transdermal delivery of beta-blockers in hairless rats and reduced skin irritation by liposomal formulation. Pharm Res 2003; 20(9): 1496-501.
[http://dx.doi.org/10.1023/A:1025726715063] [PMID: 14567646]
[2]
Green PG, Hadgraft J, Ridout G. Enhanced in vitro skin permeation of cationic drugs. Pharm Res 1989; 6(7): 628-32.
[http://dx.doi.org/10.1023/A:1015965801291] [PMID: 2798314]
[3]
Guan Y, Zuo T, Chang M, et al. Propranolol hydrochloride-loaded liposomal gel for transdermal delivery: Characterization and in vivo evaluation. Int J Pharm 2015; 487(1-2): 135-41.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.023] [PMID: 25882014]
[4]
Bhosale SS, Avachat AM. Design and development of ethosomal transdermal drug delivery system of valsartan with preclinical assessment in Wistar albino rats. J Liposome Res 2013; 23(2): 119-25.
[http://dx.doi.org/10.3109/08982104.2012.753457] [PMID: 23324030]
[5]
Mishra D, Garg M, Dubey V, Jain S, Jain NK. Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride. J Pharm Sci 2007; 96(1): 145-55.
[http://dx.doi.org/10.1002/jps.20737] [PMID: 16960826]
[6]
Tavano L, Gentile L, Oliviero Rossi C, Muzzalupo R. Novel gel-niosomes formulations as multicomponent systems for transdermal drug delivery. Colloids Surf B Biointerfaces 2013; 110: 281-8.
[http://dx.doi.org/10.1016/j.colsurfb.2013.04.017] [PMID: 23732806]
[7]
Bhaskar K, Krishna Mohan C, Lingam M, Prabhakar Reddy V, Venkateswarlu V, Madhusudan Rao Y. Development of nitrendipine controlled release formulations based on SLN and NLC for topical delivery: in vitro and ex vivo characterization. Drug Dev Ind Pharm 2008; 34(7): 719-25.
[http://dx.doi.org/10.1080/03639040701842485] [PMID: 18612912]
[8]
Krishna R, Pandit JK. Transdermal delivery of Propranolol. Drug Dev Ind Pharm 1994; 20: 2459-65.
[http://dx.doi.org/10.3109/03639049409042650]
[9]
Kumar L, Verma S, Kumar S, Prasad DN, Jain AK. Fatty acid vesicles acting as expanding horizon for transdermal delivery. Artif Cells Nanomed Biotechnol 2017; 45(2): 251-60.
[http://dx.doi.org/10.3109/21691401.2016.1146729] [PMID: 26890090]
[10]
Dhillon V, Sharma S, Jain S, Sharma A, Arora S. Formulation characterization and evaluation of new topical 5-FU by drug entrapment in oleic acid vesicles. Am J Pharm Tech Res 2011; 1: 1-16.
[11]
Aungst BJ. Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants. Pharm Res 1989; 6(3): 244-7.
[http://dx.doi.org/10.1023/A:1015921702258] [PMID: 2726682]
[12]
Verma S, Bhardwaj A, Vij M, Bajpai P, Goutam N, Kumar L. Oleic acid vesicles: a new approach for topical delivery of antifungal agent. Artif Cells Nanomed Biotechnol 2014; 42(2): 95-101.
[http://dx.doi.org/10.3109/21691401.2013.794351] [PMID: 23656670]
[13]
Zakir F, Vaidya B, Goyal AK, Malik B, Vyas SP. Development and characterization of oleic acid vesicles for the topical delivery of fluconazole. Drug Deliv 2010; 17(4): 238-48.
[http://dx.doi.org/10.3109/10717541003680981] [PMID: 20235758]
[14]
Zhang J, Xu G, Song A, et al. Faceted fatty acid vesicles formed from single-tailed perfluorinated surfactants. Soft Matter 2015; 11(36): 7143-50.
[http://dx.doi.org/10.1039/C5SM01494H] [PMID: 26252803]
[15]
Li S, Qiu Y, Zhang S, Gao Y. Enhanced transdermal delivery of 18β-glycyrrhetic acid via elastic vesicles: in vitro and in vivo evaluation. Drug Dev Ind Pharm 2012; 38(7): 855-65.
[http://dx.doi.org/10.3109/03639045.2011.630395] [PMID: 22077323]
[16]
Kumar L, Verma S, Jamwal S, Vaidya S, Vaidya B. Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization. Pharm Dev Technol 2014; 19(3): 318-25.
[http://dx.doi.org/10.3109/10837450.2013.778874] [PMID: 23560821]
[17]
Tanrıverdi ST, Özer Ö. Novel topical formulations of Terbinafine-HCl for treatment of onychomycosis. Eur J Pharm Sci 2013; 48(4-5): 628-36.
[http://dx.doi.org/10.1016/j.ejps.2012.12.014] [PMID: 23295582]
[18]
Mohamed MI. Optimization of chlorphenesin emulgel formulation. AAPS J 2004; 6(3)e26
[http://dx.doi.org/10.1208/aapsj060326] [PMID: 15760111]
[19]
El-Badry M, Fetih G, Fathalla D, Shakeel F. Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and pharmacodynamic evaluation. Pharm Dev Technol 2014; 9: 1-7.
[PMID: 24909736]
[20]
Fetih G, Fathalla D, El-Badry M. Liposomal gels for site-specific, sustained delivery of celecoxib: in vitro and in vivo evaluation. Drug Dev Res 2014; 75(4): 257-66.
[http://dx.doi.org/10.1002/ddr.21179] [PMID: 24939834]
[21]
Anraku M, Hiraga A, Iohara D, Pipkin JD, Uekama K, Hirayama F. Slow-release of famotidine from tablets consisting of chitosan/sulfobutyl ether β-cyclodextrin composites. Int J Pharm 2015; 487(1-2): 142-7.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.022] [PMID: 25882010]
[22]
Imam SS, Ahad A, Aqil M, Sultana Y, Ali A. A validated RP-HPLC method for simultaneous determination of propranolol and valsartan in bulk drug and gel formulation. J Pharm Bioallied Sci 2013; 5(1): 61-5.
[http://dx.doi.org/10.4103/0975-7406.106573] [PMID: 23559826]
[23]
Sharma A, Arora S. Dermal delivery of glucosamine sulphate: formulation, characterization and performance evaluation. World J Pharm Pharm Sci 2013; 2: 6448-62.
[24]
Mourtas S, Fotopoulou S, Duraj S, Sfika V, Tsakiroglou C, Antimisiaris SG. Liposomal drugs dispersed in hydrogels. Effect of liposome, drug and gel properties on drug release kinetics. Colloids Surf B Biointerfaces 2007; 55(2): 212-21.
[http://dx.doi.org/10.1016/j.colsurfb.2006.12.005] [PMID: 17223020]
[25]
Gill P, Moghadam TT, Ranjbar B. Differential scanning calorimetry techniques: applications in biology and nanoscience. J Biomol Tech 2010; 21(4): 167-93.
[PMID: 21119929]
[26]
Verma P, Pathak K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine 2012; 8(4): 489-96.
[http://dx.doi.org/10.1016/j.nano.2011.07.004] [PMID: 21839053]

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