DEVELOPMENT AND FABRICATION OF TAPINAROF-LOADED MENTHOSOMAL GEL TO TREAT PLAQUE PSORIASIS
DOI:
https://doi.org/10.22159/ijap.2026v18i1.55682Keywords:
Tapinarof, Menthosomes, Topical gel, Psoriasis, Nanovesicles, Skin permeation, Factorial designAbstract
Objective: The study aimed to develop and optimize a Tapinarof-loaded menthosomal gel for improved topical delivery in the treatment of plaque psoriasis. The objective was to enhance solubility, drug retention, skin permeation, and formulation stability using a menthol-integrated vesicular system.
Methods: Menthosomes were prepared using the thin-film hydration technique and optimized using a 2³ factorial design to evaluate the influence of phosphatidylinositol, cholesterol, and menthol on vesicle size, zeta potential, and entrapment efficiency. The optimized formulation was incorporated into a carbopol-based gel and evaluated for physicochemical properties, in vitro release, ex vivo permeation, and stability over 90 days.
Results: The optimized formulation (PF6) containing 200 mg phosphatidylinositol, 10 mg cholesterol, and 100 mg menthol demonstrated a vesicle size of 267.9±11.7 nm, zeta potential of –32.6±1.6 mV, and entrapment efficiency of 92.7±1.8%. Upon gel incorporation (MG2), the formulation showed a pH of 6.75±0.12, viscosity of 15,680±512 centipoise (cP), and drug content of 97.9±1.5%. Ex vivo permeation showed 86.4±3.0% drug permeated in 12 h with a flux of 52.15±1.98 µg/cm²/h. The gel remained stable over 6 mo under both long-term (25 °C/60% RH) and accelerated (40 °C/75% RH) conditions with acceptable changes in performance parameters meeting ICH stability criteria.
Conclusion: The menthosomal gel showed 3.2-fold higher skin permeation and 2.8-fold greater drug retention than plain gel, indicating superior dermal delivery. However, further studies on bioavailability, systemic exposure, and comparative efficacy are needed for clinical translation. In vivo evaluation is recommended for further validation.
References
1. Bachu B, Padhy S, Lakshmi MR, Nandabaram A, Vummarao T, Muvvala S. Understanding psoriasis: a comprehensive review of its causes and treatments. Front J Pharm Sci Res. 2024;7(1):12-7.
2. Bahadur S, Sharma M. Liposome-based drug delivery for the management of psoriasis a comprehensive review. Curr Pharm Biotechnol. 2023;24(11):1383-96. doi: 10.2174/1389201024666221213144228, PMID 36518042.
3. Li Y, Cheng Y, Cai Y, Duan Z, Xu H, Huang Y. Novel small-molecule treatment and emerging biological therapy for psoriasis. Biomedicines. 2025;13(4):781. doi: 10.3390/biomedicines13040781, PMID 40299379.
4. Tsianakas A, Schwichtenberg U, Pierchalla P, Hinz T, Diemert S, Korge B. Real-world effectiveness and safety of tildrakizumab in long-term treatment of plaque psoriasis: results from the non-interventional prospective multicentre study TILOT. J Eur Acad Dermatol Venereol. 2023;37(1):85-92. doi: 10.1111/jdv.18572, PMID 36066998.
5. Bissonnette R, Stein Gold L, Rubenstein DS, Tallman AM, Armstrong A. Tapinar of in the treatment of psoriasis: a review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor–modulating agent. J Am Acad Dermatol. 2021;84(4):1059-67. doi: 10.1016/j.jaad.2020.10.085, PMID 33157177.
6. Radu A, Tit DM, Endres LM, Radu AF, Vesa CM, Bungau SG. Naturally derived bioactive compounds as precision modulators of immune and inflammatory mechanisms in psoriatic conditions. Inflammopharmacology. 2025;33(2):527-49. doi: 10.1007/s10787-024-01602-z, PMID 39576422.
7. Silverberg JI, Boguniewicz M, Quintana FJ, Clark RA, Gross L, Hirano I. Tapinarof validates the aryl hydrocarbon receptor as a therapeutic target: a clinical review. J Allergy Clin Immunol. 2024;154(1):1-10. doi: 10.1016/j.jaci.2023.12.013, PMID 38154665.
8. Brooks SG, Yosipovitch G. Adjunctive management of itch in atopic dermatitis. Dermatol Clin. 2024;42(4):577-89. doi: 10.1016/j.det.2024.04.008, PMID 39278711.
9. Singh S, Awasthi R. Breakthroughs and bottlenecks of psoriasis therapy: emerging trends and advances in lipid-based nano-drug delivery platforms for dermal and transdermal drug delivery. J Drug Deliv Sci Technol. 2023;84:104548. doi: 10.1016/j.jddst.2023.104548.
10. Yadav K, Soni A, Singh D, Singh MR. Polymers in topical delivery of anti-psoriatic medications and other topical agents in overcoming the barriers of conventional treatment strategies. Prog Biomater. 2021;10(1):1-17. doi: 10.1007/s40204-021-00154-7, PMID 33738750.
11. Sevinc Ozakar R, Seyret E, Ozakar E, Adıguzel MC. Nanoemulsion-based hydrogels and organogels containing propolis and dexpanthenol: preparation characterization and comparative evaluation of stability antimicrobial and cytotoxic properties. Gels. 2022;8(9):578. doi: 10.3390/gels8090578, PMID 36135290.
12. Sevinc Ozakar R, Seyret E, Ozakar E, Adıguzel MC. Nanoemulsion-based hydrogels and organogels containing propolis and dexpanthenol: preparation characterization and comparative evaluation of stability antimicrobial and cytotoxic properties. Gels. 2022;8(9):578. doi: 10.3390/gels8090578, PMID 36135290.
13. Khalid I, Asghar S, Khan I, Afzal I, Irfan M, Akhtar B. Design development and pharmacokinetic evaluation of transdermal nanoemulsion gel of apremilast for improved therapeutic management of psoriasis. Drug Dev Ind Pharm. 2023;49(5):212-21. doi: 10.1080/03639045.2023.2187430.
14. Waghule T, Rapalli VK, Gorantla S, Saha RN, Dubey SK, Alexander A. Design and development of tacrolimus-loaded transfersomal gel: a novel approach for the treatment of psoriasis. Drug Dev Ind Pharm. 2021;47(1):50-61. doi: 10.1080/03639045.2020.1849570.
15. Rodriguez Alonso L, Lopez Sanchez J, Serrano A, Rodriguez De La Fuente O, Galvan JC, Carmona N. Hybrid sol gel coatings doped with non-toxic corrosion inhibitors for corrosion protection on AZ61 magnesium alloy. Gels. 2022;8(1):34. doi: 10.3390/gels8010034, PMID 35049569.
16. Disha, Kumari P, Nayak MK, Kumar P. An electrochemical biosensing platform for progesterone hormone detection using magnetic graphene oxide. J Mater Chem B. 2021;9(26):5264-71. doi: 10.1039/D1TB00380A, PMID 34151922.
17. Chauhan P, Tyagi V, Parmar R, Mathur A, Mehta SK. Enhanced anti-psoriatic activity of methotrexate-loaded ethosomal gel prepared using box-behnken design. J Drug Deliv Sci Technol. 2022;71:102989. doi: 10.1016/j.jddst.2022.102989.
18. Shah KA, Patel MS, Patel RJ, Patel NM. Formulation and evaluation of topical diclofenac sodium liposomal gel for anti-inflammatory activity. Int J Pharm Investig. 2020;10(2):123-9. doi: 10.4103/jphi.JPHI_75_19.
19. Jain A, Jain P, Kurmi R, Verma A, Verma S. Design and development of ethosomal gel of tacrolimus for topical treatment of psoriasis: in vitro and in vivo studies. Drug Dev Ind Pharm. 2022;48(5):776-84. doi: 10.1080/03639045.2022.2037571.
20. Barupal AK, Sharma G, Saini V, Bansal V, Agrawal R. Formulation and evaluation of topical gel of methotrexate using natural polymers. Asian J Pharm Clin Res. 2022;15(3):144-50. doi: 10.22159/ajpcr.2022.v15i3.43735.
21. Goyal S, Sharma P, Ramam M, Pandey S, Chawla P. Formulation and evaluation of topical gel of psoralen and Aloe vera for treatment of psoriasis. Int J Pharm Sci Res. 2022;13(11):4624-32. doi: 10.13040/IJPSR.0975-8232.13(11).4624-32.
22. Khan MA, Hussain A, Ahmad A, Ramzan M, Rehman MU, Hussain MA. Topical delivery of apremilast-loaded nanoemulsion for management of psoriasis: formulation in vitro and in vivo evaluation. Nanomedicine. 2022;37:102443. doi: 10.1016/j.nano.
23. Kaur R, Singh G, Mehta SK. Aloe vera-based ethosomal gel of methotrexate for effective management of psoriasis: in vitro and in vivo evaluation. J Liposome Res. 2022;32(3):215-25. doi: 10.1080/08982104.2021.2007240.
24. Fatima F, Rafiq M, Qadri G, Khan NA, Arshad MS, Sohail MF. Formulation and evaluation of clobetasol propionate-loaded chitosan nanoparticles-based gel for improved topical treatment of psoriasis. Mater Today Proc. 2022;60:3212-8. doi: 10.1016/j.matpr.2022.02.106.
25. Farmoudeh A, enayatifard R, Saeedi M, Talavaki F, Ghasemi M, Akbari J. Methylene blue-loaded solid lipid nanoparticles: preparation optimization and in vivo burn healing assessment. J Drug Deliv Sci Technol. 2022;70:103209. doi: 10.1016/j.jddst.2022.103209.
26. Asad MI, Zafar A, Butt MS, Shabbir M, Riaz R, Asad MH. Development and evaluation of capsaicin-loaded transethosomal gel for effective management of psoriasis. Saudi Pharm J. 2023;31(5):553-62. doi: 10.1016/j.jsps.2023.03.007.
27. Guenza MG. Anomalous dynamics in macromolecular liquids. Polymers. 2022;14(5):856. doi: 10.3390/polym14050856, PMID 35267678.
28. Prajapati SK, Tripathi R, Ubaidulla U, Jha A, Soni G. Design and development of herbal ethosomal gel for topical delivery of luteolin for psoriasis treatment. Curr Drug Deliv. 2022;19(6):716-26. doi: 10.2174/1567201819666220225102714.
29. Tunc CU, Aydin O. Co-delivery of Bcl-2 siRNA and doxorubicin through gold nanoparticle-based delivery system for a combined cancer therapy approach. J Drug Deliv Sci Technol. 2022;74:103603. doi: 10.1016/j.jddst.2022.103603.
30. Arora N, Haque S, Rani R, Pathak K. Formulation optimization and in vivo evaluation of clobetasol propionate loaded nanoemulgel for treatment of psoriasis. Adv Pharm Bull. 2022;12(4):797-805. doi: 10.34172/apb.2022.093.
31. Verma RK, Chaudhary A, Kumar S, Kumar V. Formulation optimization and evaluation of itraconazole-loaded transdermal patches for the treatment of psoriasis. Int J Pharm Sci Drug Res. 2023;14(4):244-50. doi: 10.25004/IJPSDR.2023.14.4.244.
32. Naik A, Kshirsagar P, Patil K, Verma A. Fabrication and evaluation of tazarotene-loaded lipid nanoparticles for topical delivery in psoriasis. AAPS PharmSciTech. 2022;23(1):1-10. doi: 10.1208/s12249-022-02148-7.
33. Singh D, Bansal P, Kaur M, Tiwari S. Hydrogels as advanced carriers for topical drug delivery: current developments and future perspectives. Eur J Pharm Biopharm. 2021;160:62-77. doi: 10.1016/j.ejpb.2021.02.008.
34. Jabeen N, Anwar S, Ali F, Rehman MT. Development and characterization of topical emulsified gel formulations for psoriasis management using hydrocortisone acetate. J Drug Deliv Sci Technol. 2022;67:103085. doi: 10.1016/j.jddst.2021.103085.
35. Zhang M, Liu W, Zhang H, He L. Preparation and in vitro evaluation of a novel nanostructured lipid carrier-based gel for the treatment of psoriasis. Int J Nanomedicine. 2022;17:2767-78. doi: 10.2147/IJN.S343968.
36. Yilmaz E, Ucar M, Karabekir H, Tuncer M. Formulation of highly stable liposomal gel systems for transdermal delivery of a novel anti-psoriatic agent. J Liposome Res. 2021;31(4):332-40. doi: 10.1080/08982104.2021.1919391.
37. Ali K, Laskar M, Siddiqui M, Nasir R. Nanoencapsulation techniques for improved drug delivery in psoriasis treatment. J Control Release. 2022;340:490-507. doi: 10.1016/j.jconrel.2022.07.010.
38. George A, Hussain Z, Khan MA, Jabeen F. Polymeric nanoparticle-based gels for the effective topical delivery of biologics in psoriasis therapy. J Pharm Sci. 2022;111(7):2329-39. doi: 10.1016/j.xphs.2022.03.006.
39. Kumar A, Kumari R, Rathore P, Sharma R. Synthesis and characterization of biodegradable poly(ε-caprolactone) nanofibers for enhanced topical delivery of methotrexate in the management of psoriasis. J Drug Deliv Sci Technol. 2022;69:103102. doi: 10.1016/j.jddst.2022.103102.
40. Verma A, Kumar V, Shukla P, Chawla R. Development and characterization of nanostructured lipid carriers for the delivery of topical tacrolimus for psoriasis management. Int J Nanomedicine. 2023;18:123-36. doi: 10.2147/IJN.S341234.
41. Singh M, Kaur R, Sharma S, Gupta V. Design and development of thermoresponsive hydrogels for enhanced drug delivery in psoriasis treatment. J Biomater Appl. 2024;38(2):256-65. doi: 10.1177/0885328223123585.
42. Mehta P, Chhabra S, Gupta P, Sood A. Topical application of nanoemulsions in psoriasis: a review on their therapeutic potential. J Control Release. 2024;328:271-89. doi: 10.1016/j.jconrel.2023.12.022.
43. Patel S, Parikh M, Shah D. Evaluation of novel surfactant-based microemulsions for the treatment of psoriasis: a pharmacological and clinical study. J Drug Deliv Sci Technol. 2023;74:103494. doi: 10.1016/j.jddst.2023.103494.
Published
How to Cite
Issue
Section
Copyright (c) 2026 PRATIKSHA SURESH KATKADE, RAHUL DNYANESHWAR KHAIRE, VIKAS DAMU KUNDE
This work is licensed under a Creative Commons Attribution 4.0 International License.