Author(s): Maha A. Marzouk, Asmaa M. Elbakry, Rawia M. Khalil, Areej W. Zahran

Email(s): sela.zahran@gmail.com

DOI: 10.52711/0974-360X.2022.00673   

Address: Maha A. Marzouk1, Asmaa M. Elbakry1,2*, Rawia M. Khalil3, Areej W. Zahran3*
1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt.
3Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt.
*Corresponding Author

Published In:   Volume - 15,      Issue - 9,     Year - 2022


ABSTRACT:
Carvedilol (CAR) is a cardiovascular drug commonly used for the management of hypertension, heart failure and angina pectoris. However, it has low oral bioavailability due to pre-systematic breakdown by liver enzymes which necessitates multiple doses per day. The present study investigates the development of sustained release transdermal carvedilol-loaded ethosomal formulation. CAR- ethosomal formulation was prepared by cold method with1% lipid, 50mg Carvedilol, 30% ethanol (v/v) and sonication time 3 min. The prepared formulation was characterized for vesicle size, polydispersity index (PDI) and entrapment efficiency (EE%). The formula showed small vesicle size (46.75±9.41nm) and high EE% (97%). Accordingly, it was subjected to stability study, TEM and zeta potential analysis. The formula showed good physical stability at refrigeration temperature after 90 days storage period as well as good zeta potential of +38.75mV. Our formula exhibited spherical unilamellar structure under TEM. Consequently, our formula was made as gel using HPMC polymer and was tested for pH, spreadability, drug content, skin permeation and pharmacokinetic study by HPLC-MS technique. Plasma drug levels were measured for rats after administration of both ethosomal gel and oral carvedilol tablet. The pharmacokinetic parameters were calculated and compared between the transdermal and oral dosage forms. Our formula showed lower t max and higher AUC0-24 than oral carvedilol tablet. Our findings affirm the potential of ethosomes as new vesicular carriers in sustained transdermal management of common cardiovascular conditions.


Cite this article:
Maha A. Marzouk, Asmaa M. Elbakry, Rawia M. Khalil, Areej W. Zahran. Carvedilol- loaded Transdermal Ethosomal gel: Characterization, ex vivo/in vivo Evaluation. Research Journal of Pharmacy and Technology. 2022; 15(9):4017-3. doi: 10.52711/0974-360X.2022.00673

Cite(Electronic):
Maha A. Marzouk, Asmaa M. Elbakry, Rawia M. Khalil, Areej W. Zahran. Carvedilol- loaded Transdermal Ethosomal gel: Characterization, ex vivo/in vivo Evaluation. Research Journal of Pharmacy and Technology. 2022; 15(9):4017-3. doi: 10.52711/0974-360X.2022.00673   Available on: https://rjptonline.org/AbstractView.aspx?PID=2022-15-9-33


REFERENCES:
1.    Monisha C, Ganesh G, Mythili L, Radhakrishnan K. A review on ethosomes for transdermal application. Research Journal of Pharmacy and Technology. 2019; 12(7):doi :10.5958/0974-360X.2019.00529.8  : 3133-3143.
2.    Shivhare S, Malviya K, Jain V, Negi G. A Review on Liposomes as a Novel Drug Delivery System. Research Journal of Pharmaceutical Dosage Forms and Technology. 2011; 3(5):193-198.
3.    Jain S, Jain V, Mahajan S. Lipid based vesicular drug delivery systems. Advances in Pharmaceutics. 2014; 2014:doi.org/10.1155/2014/574673 : 1-12.
4.    Bhandari S. Ethosomes: A Novel Vesicular Innovation to Enhance Transdermal Delivery of Drugs. Research Journal of Pharmaceutical Dosage Forms and Technology. 2022;14(1):DOI:10.52711/0975-4377.2022.00012 :72-78.
5.    Pandey S, Misra SK, Sharma N. Ethosomes-a novelize vesicular drug delivery system. Research Journal of Pharmacy and Technology. 2017; 10(9):DOI : 10.5958/0974-360X.2017.00572.8 : 3223-3232.
6.    Tanwar Y, Chauhan C, Sharma A. Development and evaluation of carvedilol transdermal patches. Acta Pharmaceutica. 2007; 57(2):151-159.
7.    Shivhare UD, Chopkar PT, Bhusari KP, Mathur VB, Ramteke VI. Effect of Formulation Variables on Pharmacotechnical Properties of Carvedilol Self-Emulsifying Drug Delivery System. Research Journal of Pharmaceutical Dosage Forms and Technology. 2009; 1(3):275-279.
8.    Yuvaraja K, Khanam J. Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid. Journal of Pharmaceutical and Biomedical Analysis. 2014; 96:doi.org/10.1016/j.jpba.2014.03.019 : 10-20.
9.    Vora N, Lin S, Madan P. Development and in-vitro evaluation of an optimized carvedilol transdermal therapeutic system using experimental design approach. Asian Journal of Pharmaceutical Sciences. 2013; 8(1):doi.org/10.1016/j.ajps.2013.07.004 : 28-38.
10.    Pratap SB, Brajesh K, Jain S, Kausar S. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. International Journal of Drug Development and Research 2012; 4(1):151-161.
11.    Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. Journal of Controlled Release. 2000; 65(3):doi.org/10.1016/S0168-3659(99)00222-9 : 403-418.
12.    Mishra AD, Khunt DM, Ghayal AH, Patel C, Shah DR. Formulation and optimization of ethosomes for transdermal delivery of felodipine. Research Journal of Pharmacy and Technology. 2012; 5(12):1509-1517.
13.    Sahu SK, Ram A. Evaluation of Linezolid Loaded Ethosomes for Treatment of Deep Skin Infections in Diabetic Model. Research Journal of Pharmacy and Technology. 2018; 11(7): DOI : 10.5958/0974-360X.2018.00557.7 : 3023-3030.
14.    Hajare AA, Dol HS. Screening of effective formulation techniques for Designing and Fabrication of Terbinafine hydrochloride ethosomes. Research Journal of Pharmacy and Technology. 2021; 14(3):doi: 10.5958/0974-360X.2021.00241.9 : 1353-1359.
15.    Wilson V, Siram K, Rajendran S, Sankar V. Development and evaluation of finasteride loaded ethosomes for targeting to the pilosebaceous unit. Artificial Cells, Nanomedicine, and Biotechnology. 2018; 46(8): doi.org/10.1080/21691401.2017.1396221: 1892-1901.
16.    Shen L-N, Zhang Y-T, Wang Q, Xu L, Feng N-P. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. International Journal of Pharmaceutics. 2014; 460(1-2):doi.org/10.1016/j.ijpharm.2013.11.017 : 280-288.
17.    Manconi M, Caddeo C, Sinico C, Valenti D, Mostallino MC, Lampis S, et al. Penetration enhancer-containing vesicles: composition dependence of structural features and skin penetration ability. European Journal of Pharmaceutics and Biopharmaceutics. 2012; 82(2):doi.org/10.1016/j.ejpb.2012.06.015 : 352-359.
18.    Abd El-Alim SH, Kassem AA, Basha M, Salama A. Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: in vitro and in vivo evaluation. International Journal of Pharmaceutics. 2019; 563:doi.org/10.1016/j.ijpharm.2019.04.001 : 293-303.
19.    Duarah S, Durai RD, Narayanan VB. Nanoparticle-in-gel system for delivery of vitamin C for topical application. Drug Delivery and Translational Research. 2017; 7(5):doi.org/10.1007/s13346-017-0398 : 750-760.
20.    El-Shenawy AA, Abdelhafez WA, Ismail A, Kassem AA. Formulation and characterization of nanosized ethosomal formulations of antigout model drug (febuxostat) prepared by cold method: In vitro/ex vivo and in vivo assessment. Journal of the American Association of Pharmaceutical Scientists. 2020; 21(1):doi.org/10.1208/s12249-019-1556-z : 1-13.
21.    Hashim IIA, El-Magd NFA, El-Sheakh AR, Hamed MF, Abd El AE-GH. Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study. International Journal of Nanomedicine. 2018; 13:doi:10.2147/IJN.S156412 : 1059–1079.
22.    Soliman SM, Malak NA, El-Gazayerly ON, Rehim AA. Formulation of microemulsion gel systems for transdermal delivery of celecoxib: In vitro permeation, anti-inflammatory activity and skin irritation tests. Drug discoveries and therapeutics. 2010; 4(6):459-471.
23.    Khalil RM, Abdelbary A, Kocova El-Arini S, Basha M, El-Hashemy HA. Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization. Journal of Liposome Research. 2019; 29(2):doi.org/10.1080/08982104.2018.1524482 : 171-182.
24.    Abdelwahab NS. Spectrophotometric methods for simultaneous determination of Carvedilol and Hydrochlorothiazide in combined dosage form. Arabian Journal of Chemistry. 2016; 9: doi.org/10.1016/j.arabjc.2011.05.002 : S355-S360.
25.    Lee W, Woo E, Choi J. Effects of myricetin on the bioavailability of carvedilol in rats. Pharmaceutical Biology. 2012; 50(4):doi.org/10.3109/13880209.2011.611141 : 516-522.
26.    Shumilov M, Touitou E. Buspirone transdermal administration for menopausal syndromes, in vitro and in animal model studies. International Journal of Pharmaceutics. 2010; 387(1-2):doi.org/10.1016/j.ijpharm.2009.11.029 :26-33.
27.    El-Say KM, Hosny KM. Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits. PLoS One. 2018; 13(8):doi.org/10.1371/journal.pone.0203405.
28.    Kim S-H, Lee SH, Lee HJ. Rapid and sensitive carvedilol assay in human plasma using a high-performance liquid chromatography with mass/mass spectrometer detection employed for a bioequivalence study. American Journal of Analytical Chemistry. 2010; 1(03):doi:10.4236/ajac.2010.13017 : 135-143.
29.    Jeong DW, Kim YH, Ji HY, Youn YS, Lee KC, Lee HS. Analysis of carvedilol in human plasma using hydrophilic interaction liquid chromatography with tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis. 2007; 44(2):doi.org/10.1016/j.jpba.2006.12.017 : 547-552.
30.    Mistry A, Ravikumar P. Development and evaluation of azelaic acid based ethosomes for topical delivery for the treatment of acne. Indian Journal of Pharmaceutical Education and Research. 2016; 50(3):doi:10.5530/ijper.50.3.34 : S232-243.
31.    Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical Journal of Pharmaceutical Research. 2013;12(2):doi.org/10.4314/tjpr.v12i2.20 : 265-273.
32.    Berkhout JH, Ram HA, Rathnanand M. pka determination of carvedilol by spectrophotometry. Research Journal of Pharmacy and Technology. 2021; 14(5):doi: 10.52711/0974-360X.2021.00478: 2714-2716.
33.    Kesharwani R, Patel DK, Sachan A, Kumar V, Mazumdar B. Ethosomes: A novel approach for transdermal and topical drug delivery. Research Journal of Topical and Cosmetic Sciences. 2015; 6(1):doi : 10.5958/2321-5844.2015.00003.5 :15-20.
34.    Mercier F, Lefèvre G, Aaron Huang H-L, Schmidli H, Amzal B, Appel-Dingemanse S. Rivastigmine exposure provided by a transdermal patch versus capsules. Current Medical Research and Opinion. 2007; 23(12):doi.org/10.1185/030079908X253438 : 3199-3204.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

0.38
2018CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank


Recent Articles




Tags


Not Available