Formulation and Development of Ethosomal Drug Delivery System of Silymarin for Transdermal Application
DOI:
https://doi.org/10.31351/vol33iss4pp126-140Keywords:
Ethosomes, Gel, Silymarin, Topical application, Transdermal drug deliveryAbstract
Silymarin (SM), a natural polyphenolic flavonoid, shows antidiabetic and lipid-lowering characteristics with poor aqueous solubility and bioavailability. In the current investigation, SM-incorporated ethosomes (ETO) were designed and optimized using design expert version 8.0.7.1 to overcome these pitfalls. The SM-ETO were synthesized and subjected to determine the physical appearance, percent drug entrapment, size distribution, negative charge potential, morphology study, powder crystallinity and phase transition behaviour. Following optimization, SM-ETO were added to the carbapol-containing gel and examined for pH, rheology study, drug content and in-vitro drug release study. The results manifested that SM-ETO batches did not show phase separation at 2-8°C. The batch E8 exhibited 89.67% drug entrapment, 168 nm vesicular size, 0.367 Mw polydispersity index and -0.49 mV zeta potential. A morphological study revealed elongated spherical vesicles. X-ray diffraction study exhibit the amorphous nature of SM powder. A formulated gel revealed significant pH range of 6.94 to 7.18, respectively. It also displayed 9.187 (cp) viscosity, and 96.32 to 98.45% drug content. In vitro drug release showed 96,97,94, and 98 % SM release from gel batches. The comprehensive findings explored the enhanced solubility and bioavailability of the developed gel suggesting its potential as a nanocarrier in delivering SM for future clinical applications.
How to Cite
Publication Dates
Received
Revised
Accepted
Published Online First
References
Nainwal N, Jawla S, Singh R, Saharan VA. Transdermal applications of ethosomes–a detailed review. Journal of liposome research. 2019;29(2):103-13.
Sabbagh F, Kim BS. Recent advances in polymeric transdermal drug delivery systems. Journal of controlled release. 2022;341:132-46.
Latif MS, Nawaz A, Shah MKA, Iqbal A. A Review on Transdermal Drug Delivery: Design, Evaluation and Approach towards Painless Drug Delivery System. Pharmaceutical Communications. 2022;1(01):31-45.
Witika BA, Mweetwa LL, Tshiamo KO, Edler K, Matafwali SK, Ntemi PV, et al. Vesicular drug delivery for the treatment of topical disorders: Current and future perspectives. Journal of Pharmacy and Pharmacology. 2021;73(11):1427-41.
Jafari A, Daneshamouz S, Ghasemiyeh P, Mohammadi-Samani S. Ethosomes as dermal/transdermal drug delivery systems: applications, preparation and characterization. Journal of Liposome Research. 2023;33(1):34-52.
Pandey V, Golhani D, Shukla R. Ethosomes: versatile vesicular carriers for efficient transdermal delivery of therapeutic agents. Drug delivery. 2015;22(8):988-1002.
Abdulbaqi IM, Darwis Y, Khan NAK, Assi RA, Khan AA. Ethosomal nanocarriers: The impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. International journal of nanomedicine. 2016:2279-304.
Moolakkadath T, Aqil M, Ahad A, Imam SS, Praveen A, Sultana Y, et al. Fisetin loaded binary ethosomes for management of skin cancer by dermal application on UV exposed mice. International journal of pharmaceutics. 2019;560:78-91.
Hanafy NA, El-Kemary MA. Silymarin/curcumin loaded albumin nanoparticles coated by chitosan as muco-inhalable delivery system observing anti-inflammatory and anti COVID-19 characterizations in oleic acid triggered lung injury and in vitro COVID-19 experiment. International journal of biological macromolecules. 2022;198:101-10.
Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. "Silymarin", a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011;14(4):308-17.
Archoo, Sajeeda, Shahid H. Naikoo, and Sheikh A. Tasduq. "Role of herbal products as therapeutic agents against ultraviolet radiation-induced skin disorders." Herbal Medicines. Academic Press, 2022. 345-360.
Chang L-W, Hou M-L, Tsai T-H. Silymarin in liposomes and ethosomes: Pharmacokinetics and tissue distribution in free-moving rats by high-performance liquid chromatography–tandem mass spectrometry. Journal of agricultural and food chemistry. 2014;62(48):11657-65.
Rahman HS, Othman HH, Hammadi NI, Yeap SK, Amin KM, Abdul Samad N, et al. Novel drug delivery systems for loading of natural plant extracts and their biomedical applications. International journal of nanomedicine. 2020:2439-83.
Aroraa S, Dhoke V, Moharir K, Yende S, Shah S. Novel drug delivery system of Phytopharmaceuticals: a review. Current Traditional Medicine. 2021;7(5):73-86.
Khanam, Nazia, et al. "A review on optimization of drug delivery system with experimental designs." Int J App Pharm 10.2 (2018): 7-12.
Vinod KR, Sandhya S. Factorial Designing for Pharmaceutical Product and Process Development. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 199-202.
Abdallah MH, Abu Lila AS, Shawky SM, Almansour K, Alshammari F, Khafagy E-S, et al. Experimental Design and Optimization of Nano-Transfersomal Gel to Enhance the Hypoglycemic Activity of Silymarin. Polymers. 2022;14(3):508.
Akhtar N, Varma A, Pathak K. Ethosomes as vesicles for effective transdermal delivery: from bench to clinical implementation. Current clinical pharmacology. 2016;11(3):168-90.
Paiva-Santos AC, Silva AL, Guerra C, Peixoto D, Pereira-Silva M, Zeinali M, et al. Ethosomes as nanocarriers for the development of skin delivery formulations. Pharmaceutical research. 2021;38(6):947-70.
Almajidi YQ, Maraie NK, Raauf AMR. Utilization of solid in oil nanodispersion to prepare a topical vemurafenib as potential delivery system for skin melanoma. Applied Nanoscience. 2023; 13(4): 2845-2856.
Sakdiset P, Amnuaikit T, Pichayakorn W, Pinsuwan S. Formulation development of ethosomes containing indomethacin for transdermal delivery. Journal of drug delivery science and technology. 2019;52:760-8.
Ascenso A, Raposo S, Batista C, Cardoso P, Mendes T, Praça FG, et al. Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. International journal of nanomedicine. 2015:10; 5837-51.
Limsuwan T, Amnuaikit T. Development of ethosomes containing mycophenolic acid. Procedia chemistry. 2012;4:328-35.
Ma H, Guo D, Fan Y, Wang J, Cheng J, Zhang X. Paeonol-loaded ethosomes as transdermal delivery carriers: design, preparation and evaluation. Molecules. 2018;23(7):1756.
Pathan IB, Jaware BP, Shelke S, Ambekar W. Curcumin loaded ethosomes for transdermal application: Formulation, optimization, in-vitro and in-vivo study. Journal of Drug Delivery Science and Technology. 2018;44:49-57.
Almajidi YQ, Maraie NK, Raauf AMR. Modified solid in oil nanodispersion containing vemurafenib-lipid complex-in vitro/in vivo study. F1000Research. 2022; 11(841):1-19.
Saifee M, Atre M, Toshniwal R. Formulation and In-vitro Evaluation of Ethosomal Gel of Repaglinide for Transdermal Delivery. Int J Pharm Phytopharmacol Res. 2021;11(4):11-7.
Kumar B, Sahoo P, Manchanda S. Curcumin loaded ethosomal gel for improved topical delivery: formulation, characterization and ex-vivo studies. Pharmaceutical Nanotechnology. 2021;9(4):281-7.
Ismail TA, Shehata TM, Mohamed DI, Elsewedy HS, Soliman WE. Quality by design for development, optimization and characterization of brucine ethosomal gel for skin cancer delivery. Molecules. 2021;26(11):3454.
Rossetti FC, Depieri LV, Bentley M. Confocal laser scanning microscopy as a tool for the investigation of skin drug delivery systems and diagnosis of skin disorders. Confocal laser microscopy-principles and applications in medicine, biology, and the food sciences. 2013:99-140.
Olley RC, Alhaij S, Mohsen BM, Appleton PL, Chadwick RG, Ball G. Novel Confocal-Laser-Scanning-Microscopy and conventional measures investigating eroded dentine following dentifrice dab-on and brushing abrasion. Heliyon. 2020;6(3); 1-8.
Yücel Ç, Şeker Karatoprak G, Değim İT. Anti-aging formulation of rosmarinic acid-loaded ethosomes and liposomes. Journal of microencapsulation. 2019;36(2):180-91.
Alkawak, Rasha Saadi Younus, and Nawal A. Rajab. “Lornoxicam-Loaded Cubosomes:-Preparation and In Vitro Characterization.” Iraqi Journal of Pharmaceutical Sciences. 2022; 31(1): 144-153.
Abdulbaqi, Mustafa R., and Nawal A. Rajab. "Preparation, characterization and ex vivo permeability study of transdermal apixaban O/W nanoemulsion based gel." Iraqi Journal of Pharmaceutical Sciences 2020; 29(2): 214-222.
Lian, Ruyue, et al. "Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability." Aaps Pharmscitech. 2011; 12 (4): 1234-1240.
Ismail, Muna Y., and Mowafaq M. Ghareeb. "Enhancement of the solubility and dissolution rate of rebamipide by using solid dispersion technique (Part I)." Iraqi Journal of Pharmaceutical Sciences. 2018;27(12): 55-65.
NGN, Swamy, Mazhar Pasha, and Zaheer Abbas. "Formulation and Evaluation of Diclofenac Sodium Gels Using Sodium Carboxymethyl Hydroxypropyl Guar and Hydroxypropyl Methylcellulose." Indian Journal of Pharmaceutical Education & Research. 2010; 44(4):310-314.
Jelvehgari, Mitra, Mohammad Reza Rashidi, and Hedayte Samadi. "Mucoadhesive and drug release properties of benzocaine gel.200;2(4); 185-194.
Jain, Shashank, et al. "Recent advances in lipid-based vesicles and particulate carriers for topical and transdermal application." Journal of pharmaceutical sciences. 2017; 106 (2);423-445.
Downloads
Published
License
Copyright (c) 2024 Iraqi Journal of Pharmaceutical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
