DEVELOPMENT OF LIPID-BASED VESICLES OF TERBINAFINE GEL FOR SKIN DELIVERY BY 32FULL FACTORIAL DESIGN

Authors

  • T. S. SARASWATHI Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, TamilNadu, India
  • R. ROSHINI Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, TamilNadu, India
  • N. DAMODHARAN Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, TamilNadu, India
  • M. MOTHILAL Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, TamilNadu, India
  • S. K. JANANI Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, TamilNadu, India

DOI:

https://doi.org/10.22159/ijap.2024v16i4.50460

Keywords:

Ethosomes, Terbinafine Hydrochloride, Optimization, Anti-fungal, Transdermal Enhancement

Abstract

Objective: Terbinafine is a poorly water soluble and highly permeabe allylamine antifungal (BCS-II) drug. In this study, we looked at the possibility of using ethosomes as vesicular lipid nanocarriers to enhance the transdermal delivery of terbinafine.

Methods: Using a 32 full factorial design, the ethosomal formulation with different soya lecithin and cholesterol concentrations was improved and optimized. The influence of independent variables namely soya lecithin and cholesterol concentration in ethosomes was determined by estimating dependent variable including the particle size, polydispersity index, zeta potential, entrapment efficiency, and in-vitro drug release. To improve the residence time of ethosomes on the topical application, the ethosomes were incorporated into the carbopol gel. 1% w/v of Carbopol 934 P gel-embedded Terbinafine ethosomes were used to study medication release and skin interactions.

Results: Optimized ratios of soya lecithin and cholestrol was used to prepare vesicles. Formulation had a particle size of 1207.39 ± 2.71 nm, entrapment efficiency of 94.46 ± 0.47%, and in-vitro diffusion of 51.27 ± 0.16%. It was found that the growth of fungus Aspergillus niger and Candida albicans were inhibited by Ethosomal Gel. However, ethosomal gel had more inhibitory activity on Apergillus niger compared to positive control.

Conclusion: The current study suggests that ethosomal vesicles may improve transdermal dispersion without causing skin irritation. Terbinafine-loaded ethosomes have the potential to be one of the most important transdermal application techniques for the treatment of fungi-related disorders.

Downloads

Download data is not yet available.

References

Alkhalidi HM, Hosny KM, Rizg WY. Oral Gel Loaded by Fluconazole‒Sesame Oil Nanotransfersomes: Development, Optimization, and Assessment of Antifungal Activity. Pharmaceutics. 2020;13(1):1-23. doi: http://dx.doi.org/10.3390/pharmaceutics13010027

Saifee M, Atre M, Toshniwal R. Formulation and In-vitro Evaluation of Ethosomal Gel of Repaglinide for Transdermal Delivery. Int J Pharm Phytopharm Res. 2021; 11(4): 11–17. doi: http://dx.doi.org/10.51847/lqkgwgui1l

Naheed A, Farid M, Walaa A, Fatima SA, Ali MA, Faizan A. Fabrication of Ethosomes Containing Tocopherol Acetate to Enhance Transdermal Permeation: In Vitro and Ex Vivo Characterizations. Gels. 2022; 8(6): 1-18. doi: 10.3390/gels8060335

Ivaturi Bala T, Sireesha K, Malavika B. Development of Efinaconazole nail gel for the treatment of onchomycosis. Int J App Pharm. 2024; 16(2):1-11.doi: 10.17605/OSF.IO/9P4S6

Agarwal S, Gautam G. Formulation development and characterization of ethosomes of Atorvastatin. Int Res J Pharm. 2019; 10(7): 131-36. doi: 10.7897/2230-8407.1007232

Doaa H. Hassan , Joseph N. Shohdy , Mohamed A. El-Nabarawi , Doaa Ahmed El-Setouhy, Menna M. Abdellatif. Int J App Pharm, 2022; 14(4), 88-93 doi: https://dx.doi.org/10.22159/ijap.2022v14i4.44564

Nainwal N, Jawla S, Singh R, & Saharan VA. Transdermal applications of ethosomes - a detailed review. J Lipo Res. 2019; 29(2): 103–113. doi:https://doi.org/10.1080/08982104.2018.1517160

Giri M, Bhalke R. Formulation and evaluation of topical anti-inflammatory herbal gel. Asi J Pharm and Clin Research. 2019; 12(7): 252-55. doi:10.22159/ajpcr.2019.v12i7.33859.

Nainwal N, Jawla S, Singh R, Saharan VA. Transdermal applications of ethosomes - a detailed review. J Lipo Res. 2019; 29(2): 103–113. doi: https://doi.org/10.1080/08982104.2018.1517160

Ansari SA, Qadir A, Warsi MH, Mujeeb M, Aqil M, Mir SR, Sharma S. Ethosomes-based gel formulation of karanjin for treatment of acne vulgaris: in vitro investigations and preclinical assessment. J Biotech.2021; 11(11):456-470. doi:10.1007/s13205-021-02978-3

Zahid S, Upmanyu N, Dangi S, Ray S, Jain P, Geeta P. Ethosome: a novel vesicular carrier for transdermal drug delivery. J Drug Deliv Therap.2018; 8. 318-26. doi:10.22270/jddt.v8i6.2028.

Garg BJ, Garg NK, Beg S, Singh B, Katare OP. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment. J Drug Target. 2016;24(3): 233–46. https://doi.org/10.3109/1061186X.2015.1070855

Akhtar N, Pathak K. Cavamax W7 composite ethosomal gel of clotrimazole for improved topical delivery: development and comparison with ethosomal gel. AAPS PharmSciTech. 2012; 13(1): 344–55. doi:https://doi.org/10.1208/s12249-012-9754-y

Bolla PK, Clark BA, Juluri A, Cheruvu HS, Renukuntla J. Evaluation of Formulation Parameters on Permeation of Ibuprofen from Topical Formulations Using Strat-M® Membrane. Pharmaceutics. 2020; 12(2): 151-70. doi:https://doi.org/10.3390/pharmaceutics12020151

Vedavathi T, Srinivasa rao B. Formulation and evaluation of Terbinafine hydrochloride microsponge gel. 2019. Int J App Pharm. 2018;11(6):78-85. doi: http://dx.doi.org/10.22159/ijap.2019v11i6.32502

Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: a review. Biomater Res. 2021; 25:24. doi:10.1186/s40824-021-00226-6.

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. AAPS PharmSciTech. 2019; 21(1): 31. doi:https://doi.org/10.1208/s12249-019-1556-z.

Eng N, Supraja, krishna sailaja A. Formulation of Mefenamic Acid Loaded Ethosomal Gel by Hot and Cold Methods. Nanobiomed eng. 2017; 9: 27-35. doi:10.5101/nbe.v9i1.p27-35.

Shaghlil L, Alshishani A, Abu S, Asmaa A, Hamdy A, Yousef E. Formulation and evaluation of nasal insert for nose-to-brain drug delivery of Rivastigmine tartrate. J Drug Deliv Sci Tech. 2022;76: 103736. doi :10.1016/j.jddst.2022.103736.

Jain PS, Chaudhari AJ, Patel SA, Patel ZN, Patel DT. Development and validation of the UV-spectrophotometric method for determination of terbinafine hydrochloride in bulk and in formulation. Pharm Met. 2011;2(3):198–202.doi:https://doi.org/10.4103/2229-4708.90364

Anju K, Sneh Priya, Sandeep D, Nayak, Prashant K, Pankaj K, Abhishek K, Cynthia L, Krithi SP. Formulation and optimization of Zaltoprofen loaded ethosomal gel by using 23 full factorial designs. J Pharm Res Intern.2021; 33(24B):30-44. doi:10.9734/jpri/2021/v33i24B31439.

Jain S, Tiwary AK, Sapra B, Jain NK. Formulation and evaluation of ethosomes for transdermal delivery of lamivudine.2007; AAPS PharmSciTech, 8(4), E111. doi:https://doi.org/10.1208/pt0804111

Peram MR, Jalalpure S, Kumbar V, Patil S, Joshi S, Bhat K, Diwan P. Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation.

J lipo Res. 2019; 29(3): 291–311. doi:10.1080/08982104.2018.1556292

Hajare A, Dol Hemalata S, Patil K. Design and Development of Terbinafine hydrochloride ethosomal gel for enhancement of transdermal delivery: in vitro, in vivo, molecular docking, and stability study. J Drug Deliv Sci Tech. 2020; 61. 102280. doi:10.1016/j.jddst.2020.102280.

Celebi N, Ermi S, Ozkan S. Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity. Drug dev Ind pharm.2014; 41(4): 631-39. doi:10.3109/03639045.2014.891129.

Ana AI, Marcia SC, Lucas XB, Juan L. Susceptibility test for fungi: clinical and laboratorial correlations in medical mycology. Rev Inst Med Trop Sao Paulo. 2015; 57(Suppl 19): 57–64. doi: 10.1590/S0036-46652015000700011.

Ramage G, López-Rib JL. Techniques for Antifungal Susceptibility Testing of Candida albicans Biofilms.In: Ernst, E.J., Rogers, P.D. (eds) Antifungal Agents. Methods in Molecular Medicine™. 2005; 118. Humana Press. doi: 10.1385/1-59259-943-5:071

Xiao-Qian N, Dan-Ping Z, Qiong B, Xing-Fu F, Hao L, Yue-Feng R, Yong-Mei S, Fu-Neng G, An-Ran Y, Xiao-Ying Y, Jian-Qing G. Mechanism investigation of ethosomes transdermal permeation. Int J Pharm: X.2019; 1: 100027. doi:10.1016/j.ijpx.2019.100027.

Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J cont release.2005; 106(1-2): 99–110. doi:https://doi.org/10.1016/j.jconrel.2005.04.007

Kaur M, Singh K, Jain SK. Luliconazole vesicular based gel formulations for its enhanced topical delivery. J lipo Res.2020;30(4):388–406. doi:10.1080/08982104.2019.1682602

Sinico C, Fadda AM. Vesicular carriers for dermal drug delivery. Exp opin drug deliv. 2009; 6(8): 813–25. doi:https://doi.org/10.1517/17425240903071029

Pathan BI, Bhaktraj PJ, Santosh S, Ambekar W. Curcumin loaded ethosomes for transdermal application: Formulation, optimization, in-vitro and in-vivo study. J Drug Deliv Sci Tech. 2018;44: 49-57.doi:10.1016/j.jddst.2017.11.005.

Selvamuthukumar R, Murali R, Srinivasan N, Mohankumar A, Nitin P. Formulation Development and Evaluation of Immediate release tablet of Terbinafine Hydrochloride. Res J Pharm Tech.2020;13(10):4648-54.doi:10.5958/0974-360X.2020.00818.5

Anggraini YE, Trisnowati N, Martien R, Danarti R. A randomised clinical trial study assessing the efficacy of 5% losartan potassium loaded in ethosomal gel to treat human keloids: a trial protocol.2024; Trials 25, 12.doi:10.1186/s13063-023-07880-2.

Paresh M, Sarika AN, Chavan MS. Development and Evaluation of Terbinafine Hydrochloride Polymeric Microsponges for Topical Drug Delivery.Ind J Pharm Sci. 2018;80(6): doi:10.4172/pharmaceutical-sciences.1000459

Shamma, RN, Elsayed I. Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization. J lipo res. 2013; 23(3): 244–54. doi:10.3109/08982104.2013.801489

Maha H, Sinaga K, Masfria M. Formulation and evaluation of miconazole nitrate nanoemulsion and cream. Asian J Pharm Clin Res. 2018; 11(3): 319-21. doi:10.22159/ajpcr.2018.v11i3.22056.

Pawar H, Attarde V, Gide P. Optimization of Bifonazole-Loaded Nisomal Formulation Using Plackett-Burman Design and 2 Factorial Design. Open Pharm Sci J. 2016;3: 31-48. doi:10.2174/1874844901603010031.

Vaghasiya H, Kumar A, Sawant K. Development of Solid Lipid Nanoparticles Based Controlled Release System for Topical Delivery of Terbinafine Hydrochloride. Euro j pharm Sci.2013;49:doi:10.1016/j.ejps.2013.03.013.

Khan R, Saif Dr, Naureen H, Sarwar A, Shahbaz M, Arif M. Formulation and Evaluation of Metronidazole Loaded Nanosponges for Topical Delivery. Pharm Com. 2022; 1: 71-87. doi:10.55627/pharma.001.001.0185.

Shen LN, Zhang YT, Wang Q, Xu L, Feng NP. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Int J Pharm. 2014; 460(1-2): 280–88. doi:https://doi.org/10.1016/j.ijpharm.2013.11.017

Published

15-05-2024

How to Cite

SARASWATHI, T. S., ROSHINI, R., DAMODHARAN, N., MOTHILAL, M., & JANANI, S. K. (2024). DEVELOPMENT OF LIPID-BASED VESICLES OF TERBINAFINE GEL FOR SKIN DELIVERY BY 32FULL FACTORIAL DESIGN. International Journal of Applied Pharmaceutics, 16(4). https://doi.org/10.22159/ijap.2024v16i4.50460

Issue

Section

Original Article(s)