Design, Optimization, and Characterization of Tranexamic Acid Microemulsion for Topical Delivery
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 208-222
https://doi.org/10.22037/ijps.v22i1.45865
Abstract
This study focuses on the design, optimization, and evaluation of tranexamic acid (TXA) microemulsions (ME-TXA) for topical delivery to manage melasma. TXA is an antifibrinolytic agent that competitively inhibits plasminogen activation and acts as a non-competitive plasmin inhibitor, reducing melanin synthesis and inflammation in pigment cells. Beyond melasma, TXA has demonstrated potential for treating various skin disorders, including post-inflammatory hyperpigmentation, melanin-related pigmentation disorders [1], and chronic inflammatory conditions such as atopic dermatitis and rosacea [2]. Studies suggest that TXA can be beneficial in treating melasma [3].
The microemulsions were formulated using Labrafac PG/Transcutol P as the oil phase, Tween 80 and Span 80 as surfactants, and propylene glycol (PG) (10:1 ratio) as a co-surfactant These systems offer advantages such as improved drug solubility, enhanced skin penetration, controlled release, and increased formulation stability, making them ideal for topical delivery of TXA [4]. Physicochemical properties, including particle size, viscosity, zeta potential, and permeability, were systematically analyzed. Characterization of the formulations demonstrated particle sizes ranging from 15.08 to 34.75 nm, viscosities between 147.83 and 300.3 cps, and zeta potentials from -1.7 to -13.2 mV, ensuring stability and homogeneity.
In vitro release studies indicated a cumulative drug release of up to 99.3% over 24 hours, following first-order release kinetics. The optimized formulation demonstrated enhanced TXA solubility, stability, and controlled drug release compared to aqueous solutions.
Skin permeation studies revealed significantly enhanced drug permeation, with the optimized formulation achieving a steady-state flux (Jss) of 5.544 mg/cm²·h and a permeability coefficient (P) of 0.1108 cm/h.
In addition, the apparent diffusion coefficient (Dapp) analysis demonstrated a reduced lag time (Tlag) compared to aqueous TXA.”
These findings highlight the potential of ME-TXA as a biocompatible and efficient drug delivery system, offering improved solubility, stability, controlled release, and enhanced transdermal permeability for the effective management of melasma.
- Tranexamic Acid
- Microemulsion
- Melasma
- Optimization
- Topical
How to Cite
References
1. Noguchi N, Hirose T, Suzuki T, Kagaya M, Chida K, Ohno S, et al. Atypical protein kinase C isoforms differentially regulate directional keratinocyte migration during wound healing. Journal of Dermatological Science. 2019;93(2):101-8.
2. Prudovsky I, Kacer D, Zucco VV, Palmeri M, Falank C, Kramer R, et al. Tranexamic acid: beyond antifibrinolysis. Transfusion. 2022;62:S301-S12.
3. Wang JV, Jhawar N, Saedi N. Tranexamic acid for melasma: evaluating the various formulations. The Journal of Clinical and Aesthetic Dermatology. 2019;12(8):E73.
4. Venditto VJ, Szoka FC. Cancer nanomedicines: So many papers and so few drugs! Advanced Drug Delivery Reviews. 2013;65(1):80-8.
5. Gruen RL, Jacobs IG, Reade MC. Tranexamic acid and trauma. The Medical journal of Australia. 2014;200(5):255.
6. Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013;7:CD010562.
7. Lukes AS, Freeman EW, Van Drie D, Baker J, Adomako TL. Safety of tranexamic acid in women with heavy menstrual bleeding: an open-label extension study. Women’s Health. 2011;7(5):591-8.
8. Tse TW, Hui E. Tranexamic acid: an important adjuvant in the treatment of melasma. Journal of cosmetic dermatology. 2013;12(1):57-66.
9. Padhi T, Pradhan S. Oral tranexamic acid with fluocinolone-based triple combination cream versus fluocinolone-based triple combination cream alone in melasma: an open labeled randomized comparative trial. Indian journal of dermatology. 2015;60(5):520.
10. Cho HH, Choi M, Cho S, Lee JH. Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS Nd: YAG laser. Journal of Dermatological Treatment. 2013;24(4):292-6.
11. Weide I, Simmet T. Novel mode of monocyte 5-lipoxygenase stimulation. Advances in prostaglandin, thromboxane, and leukotriene research. 1995;23:325.
12. Syrovets T, Tippler B, Rieks M, Simmet T. Plasmin is a potent and specific chemoattractant for human peripheral monocytes acting via a cyclic guanosine monophosphate–dependent pathway. Blood. 1997;89(12):4574-83.
13. Maeda K, Tomita Y. Mechanism of the inhibitory effect of tranexamic acid on melanogenesis in cultured human melanocytes in the presence of keratinocyte-conditioned medium. Journal of health science. 2007;53(4):389-96.
14. Maeda K, Naganuma M. Topical trans-4-aminomethylcyclohexanecarboxylic acid prevents ultraviolet radiation-induced pigmentation. Journal of Photochemistry and Photobiology B: Biology. 1998;47(2-3):136-41.
15. Tan AWM, Sen P, Chua SH, Goh BK. Oral tranexamic acid lightens refractory melasma. Australasian Journal of Dermatology. 2017;58(3):e105-e8.
16. Na J, Choi S, Yang S, Choi H, Kang H, Park KC. Effect of tranexamic acid on melasma: a clinical trial with histological evaluation. Journal of the European Academy of Dermatology and Venereology. 2013;27(8):1035-9.
17. Ogbechie-Godec OA, Elbuluk N. Melasma: an up-to-date comprehensive review. Dermatology and therapy. 2017;7(3):305-18.
18. Cohen PR. Melasma treatment: A novel approach using a topical agent that contains an anti-estrogen and a vascular endothelial growth factor inhibitor. Medical hypotheses. 2017;101:1-5.
19. JO HY, KIM CK, SUH IB, RYU SW, HA KS, KWON YG, et al. Co‐localization of inducible nitric oxide synthase and phosphorylated Akt in the lesional skins of patients with melasma. The Journal of dermatology. 2009;36(1):10-6.
20. Nautiyal A, Wairkar S. Management of hyperpigmentation: Current treatments and emerging therapies. Pigment Cell Melanoma Res. 2021;34(6):1000-14.
21. Manosroi A, Podjanasoonthon K, Manosroi J. Development of novel topical tranexamic acid liposome formulations. International Journal of Pharmaceutics. 2002;235(1):61-70.
22. Wu H, Ramachandran C, Weiner ND, Roessler BJ. Topical transport of hydrophilic compounds using water-in-oil nanoemulsions. International Journal of Pharmaceutics. 2001;220(1):63-75.
23. Alissa M, Hjazi A, Abusalim GS, Aloraini GS, Alghamdi SA, Rizg WY, et al. Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal. Pharmaceutics [Internet]. 2023; 15(9).
24. Mariyate J, Bera A. A critical review on selection of microemulsions or nanoemulsions for enhanced oil recovery. Journal of Molecular Liquids. 2022;353:118791.
25. Liu P, Chen G, Zhang J. A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules. 2022;27.
26. Al-Suwayeh SA, Taha EI, Al-Qahtani FM, Ahmed MO, Badran MM. Evaluation of skin permeation and analgesic activity effects of carbopol lornoxicam topical gels containing penetration enhancer. The Scientific World Journal. 2014;2014.
27. Manosroi A, Podjanasoonthon K, Manosroi J. Development of novel topical tranexamic acid liposome formulations. International journal of pharmaceutics. 2002;235(1-2):61-70.
28. Williams A. barry B. w., Penetration Enhancers, Adv. Drug delivery ststems, Rev. 2004;56:603-18.
29. Zadeh B, Moghimi H, Santos P, Hadgraft J, Lane ME, Rahim F. Formulation of microemulsion systems for improvement of nitrofurazone permeation through silicon membrane as burn wound imitating coverage. INTERNATIONAL JOURNAL OF PHARMACOLOGY. 2010;6(3):264-70.
30. Wilk KA, Zielińska K, Hamerska-Dudra A, Jezierski A. Biocompatible microemulsions of dicephalic aldonamide-type surfactants: formulation, structure and temperature influence. J Colloid Interface Sci. 2009;334(1):87-95.
31. Moghimipour E, Salimi A, Leis F. Preparation and evaluation of tretinoin microemulsion based on pseudo-ternary phase diagram. Advanced pharmaceutical bulletin. 2012;2(2):141.
32. Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S. Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta pharmaceutica. 2007;57(3):315-32.
33. Moghimipour E, Salimi A, Eftekhari S. Design and characterization of microemulsion systems for naproxen. Advanced pharmaceutical bulletin. 2013;3(1):63.
34. Yue Y, LI S-m, YU L-m, Pan D, ZHONG D-f. Physicochemical properties and evaluation of microemulsion systems for transdermal delivery of meloxicam. Chemical Research in Chinese Universities. 2007;23(1):81-6.
35. de Campos Araújo LMP, Thomazine JA, Lopez RFV. Development of microemulsions to topically deliver 5-aminolevulinic acid in photodynamic therapy. European journal of pharmaceutics and biopharmaceutics. 2010;75(1):48-55.
36. Megrab NA, Williams A, Barry B. Oestradiol permeation through human skin and silastic membrane: effects of propylene glycol and supersaturation. Journal of controlled release. 1995;36(3):277-94.
37. Bhonge A. Microemulsion-Based Drug Delivery Systems: Harnessing Nanostructures for Enhanced Therapeutic Efficacy. Journal of Drug Delivery and Biotherapeutics. 2024;1(01):31-9.
38. Moulik SP, Paul BK. Structure, dynamics and transport properties of microemulsions. Advances in Colloid and Interface science. 1998;78(2):99-195.
39. Onaizi SA. Effect of oil/water ratio on rheological behavior, droplet size, zeta potential, long-term stability, and acid-induced demulsification of crude oil/water nanoemulsions. Journal of Petroleum Science and Engineering. 2022;209:109857.
40. Buyukozturk F, Benneyan JC, Carrier RL. Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics. Journal of controlled release. 2010;142(1):22-30.
41. Silva HD, Cerqueira MA, Vicente AA. Influence of surfactant and processing conditions in the stability of oil-in-water nanoemulsions. Journal of Food Engineering. 2015;167:89-98.
42. Mehta S, Kaur G, Bhasin K. Incorporation of antitubercular drug isoniazid in pharmaceutically accepted microemulsion: effect on microstructure and physical parameters. Pharmaceutical research. 2008;25(1):227-36.
43. Rosano HL, Clausse M. Microemulsion systems: Crc Press; 1987.
44. Lagues M, Sauterey C. Percolation transition in water in oil microemulsions. Electrical conductivity measurements. The Journal of Physical Chemistry. 1980;84(26):3503-8.
45. Hiemenz PC, Rajagopalan R. Principles of Colloid and Surface Chemistry, revised and expanded: CRC press; 2016.
46. Zvonar A, Rozman B, Rogač MB, Gašperlin M. The Influence of Microstructure on Celecoxib Release from a Pharmaceutically Applicable System: Mygliol 812/Labrasol/Plurol Oleique;/Water Mixtures. Acta Chimica Slovenica. 2009;56(1).
47. Kumar M, Jain C, Shukla AK, Verma G, Yadav VK. Terminology and Mechanisms of Self-Emulsifying Systems for Biomedical Applications: A Comprehensive Review. Colloid Journal. 2023;85(6):917-29.
48. Patel S, Vyas J, Upadhyay U. Nanoemulsion: Methods and application in drug delivery.
49. Froelich A, Osmałek T, Snela A, Kunstman P, Jadach B, Olejniczak M, et al. Novel microemulsion-based gels for topical delivery of indomethacin: Formulation, physicochemical properties and in vitro drug release studies. Journal of colloid and interface science. 2017;507:323-36.
50. Cázares-Delgadillo J, Naik A, Kalia Y, Quintanar-Guerrero D, Ganem-Quintanar A. Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon. International journal of pharmaceutics. 2005;297(1-2):204-12.
51. Carpentieri-Rodrigues LN, Zanluchi JM, Grebogi IH. Percutaneous absorption enhancers: Mechanisms and potential. Brazilian Archives of Biology and Technology. 2007;50:949-61.
52. Sinha V, Kaur MP. Permeation enhancers for transdermal drug delivery. Drug development and industrial pharmacy. 2000;26(11):1131-40.
53. Shen W-W, Danti AG, Bruscato FN. Effect of nonionic surfactants on percutaneous absorption of salicylic acid and sodium salicylate in the presence of dimethyl sulfoxide. Journal of Pharmaceutical Sciences. 1976;65(12):1780-3.
54. Soleymani SM, Salimi A. Enhancement of dermal delivery of finasteride using microemulsion systems. Advanced Pharmaceutical Bulletin. 2019;9(4):584.
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