ABSTRACT:
This study was intended to develop and optimize Tranexamic acid (TXA) loaded transethosomal (TEL’s) patch for the treatment of melasma. Upon oral administration, TXA is reported to cause gastrointestinal (GI) sideeffects and showed 30-50% bioavailability. Hence an alternative transdermal drug delivery system has been designed in the form of transethosomes (TEL). TXA loaded TELwere prepared by the cold method using Phospholipon 90G as a lipoid, sodium cholate as an edge activator, ethanol, and water. Further size reduction was done using a probe sonicator. For optimization purposes central composite design (CCD) was used. Phospholipon 90G and sodium cholate were selected as independent variables. Particle size (PS) and entrapment efficiency (E.E) were selected as a response. Mathematical equations and 3-D response surface graphs were used to relate dependant and independent variables. The optimized model pre-predicted and experimentally gave the particle size of 72nm, zeta potential of -16mV, encapsulation efficiency of 94%, with an enhanced transdermal flux of 32.85µg/cm2 /h as compared to a conventional topical cream. In vitro and ex-vivo studies were done to check the efficacy of the formulation and the results showed improved release of drug in TEL formulation as compared to conventional marketed formulation.
Cite this article:
Jessy Shaji, Shamika S. Parab. CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma. Research Journal of Pharmacy and Technology 2023; 16(4):1549-5. doi: 10.52711/0974-360X.2023.00253
Cite(Electronic):
Jessy Shaji, Shamika S. Parab. CCD based Development and Characterization of Tranexamic acid Loaded Transethosomes for Melasma. Research Journal of Pharmacy and Technology 2023; 16(4):1549-5. doi: 10.52711/0974-360X.2023.00253 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-4-1
REFERENCES:
1. Grimes PE, et al. New oral and topical approaches for the treatment of melasma. International Journal of Women's Dermatology. 2018 Nov 20;5(1):30-36.doi:10.1016/j.ijwd.2018.09.004.
2. George A. Tranexamic acid: An emerging depigmenting agent. Pigment Int 2016;3(2): 66–71.doi: 10.4103/2349-5847.196295.
3. Taraz M, et al. Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies. Dermatol Ther 2017;30(3): e12465.doi:10.1111/dth.12465
4. Cai J, et al. The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients. European journal of haematology 2020; 104(2): 79-87.doi:10.1111/ejh.13348.
5. Sheu SL. Treatment of melasma using tranexamic acid: what's known and what's next. Cutis 2018;101(2):E7–E8.
6. Xu Y, et al. Efficacy of functional microarray of microneedles combined with topical tranexamic acid for melasma: A randomized, self-controlled, split-face study. Medicine (Baltimore) 2017; 96(19): e6897.doi:10.1097%2FMD.0000000000006897
7. Del Rosario, et al. Randomized, placebo-controlled, double-blind study of oral tranexamic acid in the treatment of moderate-to-severe melasma. Journal of the American Academy of Dermatology 2018; 78(2): 363-369.doi:10.1016/j.jaad.2017.09.053
8. Kaur A, et al. Tranexamic acid in melasma: a review. Pigment Int 2020;7(1):12-25.doi: 10.4103/Pigmentinternational.Pigmentinternational_
9. Tan AWM, et al. Oral tranexamic acid lightens refractory melasma. Australas J Dermatol 2017;58(3):e105-e108.doi:10.1111/ajd.12474.
10. Zhang L, et al. Tranexamic acid for adults with melasma: a systematic review and meta-analysis. BioMed research international 2018; doi:10.1155/2018/1683414.
11. Grimes PE., et al. New oral and topical approaches for the treatment of melasma. International Journal of Women’s Dermatology 2018; 5(1): 30–36.doi:10.1016/j.ijwd.2018.09.004.
12. Rodrigues M, Pandya A. Melasma: Clinical diagnosis and management options. Australas J Dermatol 2015;56(3):151–63.doi:10.1111/ajd.12290.
13. Sarkar R., et al. Melasma in men: A review of clinical, etiological, and management issues. The Journal of clinical and aesthetic dermatology 2018 11(2), p.53-59.
14. Ikino JK, et al. Melasma and assessment of the quality of life in Brazilian women. An Bras Dermatol 2015;90(2):196–200.doi:10.1590/abd1806-4841.20152771
15. Aishwarya K, et al. Current concepts in melasma - A review article. J Skin Sex Transm Dis 2020;2(1):13-17.doi: 10.25259/JSSTD_34_2019
16. Sandeep Gupta, Dheeraj Ahirwar, Neeraj K Sharma, DeenanathJhade. Proniosomal Gel as a Carrier for Improved Transdermal Delivery of Griseofulvin: Preparation and In vitro Characterization. Research J. Pharma. Dosage Forms and Tech. 2009; 1(1): 33-37.
17. Pawar P et als. Different Techniques for Preparation of Nanosuspension with Reference to its Characterisation and various Applications - A Review. Asian J. Res. Pharm. Sci. 2018; 8(4): 210-216. doi: 10.5958/2231-5659.2018.00035.8
18. Bajaj KJ, et al. Nano-transethosomes: A Novel Tool for Drug Delivery through Skin. Indian J of Pharmaceutical Education and Research 2021;55 Suppl 1:1-10.doi: 10.5530/ijper.55.1s.33.
19. Gondkar SB, et al. Formulation Development and Characterization of Etodolac Loaded Transethosomes for Transdermal Delivery. Research J. Pharm. And Tech. 2017; 10(9):3049-3057. doi:10.5958/0974-360X2017.00541.8.
20. Phatak Atul A., Chaudhari Praveen D. Development and Evaluation of Nanogel as a Carrier for Transdermal Delivery of Aceclofenac. Asian J. Pharm. Tech, 2012; 2(4): 125-132.
21. Kumara Swamy S, Ramesh Alli. Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery. Asian Journal of Pharmacy and Technology. 2021; 11(2):97-4. doi: 10.52711/2231-5713.2021.00016
22. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 1). Trop J Pharm Res. 2013;12(2):255-64.doi:10.4314/tjpr.v12i2.19.
23. Jessy Shaji, Monika Kumbhar. Linezolid Loaded Biodegradable Polymeric Nanoparticles Formulation and Characterization. Res. J. Pharm. Dosage Form. & Tech. 2018; 10(4): 272-278. doi: 10.5958/0975-4377.2018.00040.X
24. Varshosaz, J, et al. Lipid Nanocapsule-Based Gels for Enhancement of transdermal Delivery of Ketorolac Tromethamine. J. Drug Deliv. 2011,2011, 1-7.doi: 10.1155/2011/571272.
25. Wu IY, et al. Interpreting non-linear drug diffusion data: Utilizing Korsmeyer-Peppas model to study drug release from liposomes. Eur J Pharm Sci. 2019 October 1;138: 105026.doi: 10.1016/j.ejps.2019.105026.
26. D.R. Paul. Elaborations on the Higuchi model for drug delivery. Int J Pharm. 2011;418:13-17. doi:10.1016/j.ijpharm.2010.10.037.
27. Rehman Q, et al. Role of Kinetic Models in Drug Stability. In: Akash M.S.H., Rehman K. (eds).Drug Stability and Chemical Kinetics. Springer, Singapore.2020 Nov 02;155-165.doi:10.1007/978-981-15-6426-0_11.
28. Singhvi G, Singh M. In vitro drug release characterization models. Int J Pharm Stud Res. 2011;2:77-84.
29. Yang Z, et al. Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency. Int. J. Pharm. 2020:119006. doi:10.1016/j.ijpharm.2019.119006.
30. Shaji J, Garude S. Transethosomes and Ethosomes for Enhanced Transdermal Delivery of Ketorolac Tromethamine : A Comparative Assessment. International Journal of Current Pharmaceutical Research. 2014;6(4):88 - 93.
31. Vinod K.R., Sandhya S. Factorial Designing for Pharmaceutical Product and Process Development. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 199-202.
32. Tipre DN, Vavia PR. Formulation optimization and stability study of transdermal therapeutic system of nicorandil. Pharm. Dev. Technol. 2002;7:325–32.doi:10.1081/PDT-120005729.
33. Sinico, C, et al. Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle–skin interaction. Journal of Controlled Release 2005;103(1):123–136.doi:10.1016/j.jconrel.2004.11.020.
34. K.Vijaya S et al. Formulation and Evaluation of Rutin Loaded Nanosponges. Asian J. Res. Pharm. Sci. 2018; 8(1):21-24. doi: 10.5958/2231-5659.2018.00005.X
35. Shaji, J., and S. Garude. “Transethosomes and Ethosomes FOR enhanced Transdermal Delivery of Ketorolac Tromethamine: A Comparative Assessment”. International Journal of Current Pharmaceutical Research 2014;6(4):88-93.
36. Talib S, et al. Chitosan-chondroitin based artemether loaded nanoparticles for transdermal drug delivery system. Journal of Drug Delivery Science and Technology 2021; 61: p.102281.doi:10.1016/j.jddst.2020.102281.
37. Saraswathi B et al. Formulation and Characterization of Tramadol HCl Transdermal Patch. Asian J. Pharm. Tech. 2018; 8 (1):23-28 . doi: 10.5958/2231-5713.2018.00004.1
38. Salve P et al. Formulation and Evaluation of Solid Lipid Nanoparticle Based Transdermal Drug Delivery System for Alzheimer’s Disease. Res. J. Pharm. Dosage Form. and Tech. 2016; 8(2):73-80. doi: 10.5958/0975-4377.2016.00011.2