Comparative study of the adhesive properties of transdermal patches with trans-resveratrol using the probe tack test

Introduction. Transdermal Therapeutic Systems (TTS), particularly transdermal patches, represent one of the most promising non-invasive routes for delivering drugs into the systemic circulation. A key prerequisite for realizing the therapeutic potential of transdermal patches is the maintenance of stable and uniform contact between the system and the skin surface throughout the intended period of use, achieved through optimal adhesive characteristics. The adhesion of TTS is a critical quality attribute (CQA) that determines drug bioavailability and patient safety, and it requires objective assessment that takes into account skin biomechanics and real-use conditions.

Aim. A comparative analysis of adhesive properties of transdermal patches with the phytoestrogen trans-resveratrol using the probe tack test.

Materials and methods. The objects of the study were matrix-type patch samples obtained at the St. Petersburg State Chemical and Pharmaceutical University (SPCPU) of the Ministry of Health of the Russian Federation, containing trans-resveratrol. Adhesion was evaluated by probe tack test using the texture analyzer TA.XTplus with Exponent Connect software. The study was conducted at the Institute of Pharmacy, Kazan State Medical University (KSMU) of the Ministry of Health of the Russian Federation. Transdermal patches Nicorette® and Evra® (LTS Lohmann Therapy-Systems AG, Germany) were used as comparator products (positive controls). Two types of substrates were used to model human skin: a biological substrate (isolated pig skin) and a synthetic substrate (silicone skin). The test results were processed using standard statistical methods in accordance with the requirements of the State Pharmacopoeia of the Russian Federation.

Results and discussion. The patch sample based on a copolymer of methacrylic acid and ethyl acrylate as a polymer carrier acting as an adhesive demonstrated the highest tack, comparable to that of the reference products. The incorporation of polyvinylpyrrolidone K-17 to enhance the release of trans-resveratrol from the matrix resulted in a partial loss of patch adhesion and the formation of an unstable system that was highly sensitive to environmental conditions.

Conclusion. Based on the evaluation of peak force required to break the bond and work of adhesion, it was established that the use of a copolymer of methacrylic acid and ethyl acrylate for the development of matrix-type transdermal patches with trans-resveratrol represents a promising approach. This strategy enables an optimal combination of adhesive properties, comparable to those of reference products, while maintaining the active substance release performance from the TTS as reported in a previous study.

1. Wang L., Ma J., Li J., Fang L., Liu C. Transdermal patch based on pressure-sensitive adhesive: the importance of adhesion for efficient drug delivery. Expert Opinion on Drug Delivery. 2025;22(3):405–420. https://doi.org/10.1080/17425247.2025.2460650

2. Al-Smadi K., Ali M., Zhu J., Abdoh A., Phan K., Mohammed Y. Advances in Characterization of Transdermal and Topical Products using Texture Analyzer Systems. AAPS PharmSciTech. 2025;26(5):157. https://doi.org/10.1208/s12249-025-03148-x

3. Yakimov K. D., Nogaeva U. V., Flisyuk E. V. Adhesion as a quality attribute of transdermal therapeutic systems: analysis of requirements, evaluation methods. Pharmaceutical Chemistry Journal. 2025;59(12):125–137. (In Russ.) https://doi.org/10.30906/0023-1134-2025-59-12-40-49

4. Bozorg B. D., Banga A. K. Effect of Different Pressure-Sensitive Adhesives on Performance Parameters of Matrix-Type Transdermal Delivery Systems. Pharmaceutics. 2020;12(3):209. https://doi.org/10.3390/pharmaceutics12030209

5. Yakimov K. D., Nogaeva U. V., Flisyuk E. V. Development and pharmacotechnological studies of transdermal patches with trans-resveratrol. Drug development & registration. 2025;14(4):125–137. (In Russ.) https://doi.org/10.33380/2305-2066-2025-14-4-2198

6. Sadkovskii I. A., Korol L. A., Karabanova A. B., Korolenko A. V., Shemetova E. A., Krasnyuk I. I., Ramenskaya G. V., Mandrik M. A. Test methods for adhesive polymer compositions in development and quality control for stoma care products on the example of adhesive baseplates (review). Drug development & registration. 2025;14(2):156–169. (In Russ.). https://doi.org/10.33380/2305-2066-2025-14-2-2031

7. Jin Y., Song Z., Zhang R., Zhang J. Experiment and analysis of physical, mechanical, and viscoelastic properties of the roots and stalks of green leafy vegetables. PLoS ONE. 2024;19(7):e0305572. https://doi.org/10.1371/journal.pone.0305572

8. Sharafi S., Nateghi L., Eyvazzade O., Ebrahimi M. T. A. The physicochemical, texture hardness and sensorial properties of ultrafiltrated low-fat cheese containing galactomannan and novagel gum. Acta Scientiarum Polonorum. Technologia Alimentaria. 2020;19(1):83–100. https://doi.org/10.17306/J.AFS.0685

9. Christofi M., Mourtzinos I., Lazaridou A., Drogoudi P., Tsitlakidou P., Biliaderis C. G., Manganaris G. A. Elaboration of novel and comprehensive protocols toward determination of textural properties and other sensorial attributes of canning peach fruit. Journal of Texture Studies. 2021;52(2):228–239. https://doi.org/10.1111/jtxs.12577

10. Rafferty D. W., Dupin L., Zellia J., Giovannitti-Jensen A. Predicting lipstick sensory properties with laboratory tests. International Journal of Cosmetic Science. 2018;40(5):451–460. https://doi.org/10.1111/ics.12482

11. Bîrsan M., Cristofor A. C., Tuchiluş C., Crivoi F., Vlad R. A., Pintea C., Antonoaea P., Ciurba A. Development of cream bases suitable for personalized cosmetic products. Medicine and Pharmacy Reports. 2024;97(3):347–356. https://doi.org/10.15386/mpr-2765

12. Rony F. K., Appiah J., Alawbali A., Clay D., Ilias S., Azad M. A. Evaluating Swellable Cross-Linked Biopolymer Impact on Ink Rheology and Mechanical Properties of Drug-Contained 3D-Printed Thin Film. Pharmaceutics. 2025;17(2):183. https://doi.org/10.3390/pharmaceutics17020183

13. Irmukhametova G. S., Makhayeva D. N., Kozhantayeva Zh., Khutoryanskiy V. V. Synthesis and study of mucoadhesive properties of thiolated polymers based on polyhydroxyethylmethacrylate and 3-mercaptopropyltrimethoxysilane. Chemical Journal of Kazakhstan. 2024;4(88):14–24. (In Russ.) https://doi.org/10.51580/2024-4.2710-1185.44

14. Moustafine R. I., Budnikov V. V., Abdullina S. G., Nasibullin Sh. F., Saleev R. A. Polycomplex Carrier for Buccal Mucoadhesion Delivery of Metronidazole. Drug development & registration. 2020;9(2):83–90. (In Russ.) https://doi.org/10.33380/2305-2066-2020-9-2-83-90

15. Hoang M. T., Ita K. B., Bair D. A. Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and Pramipexole Dihydrochloride. Pharmaceutics. 2015;7(4):379–396. https://doi.org/10.3390/pharmaceutics7040379

16. Uhm C., Jeong H., Lee S. H., Hwang J. S., Lim K.-M., Nam K. T. Comparison of structural characteristics and molecular markers of rabbit skin, pig skin, and reconstructed human epidermis for an ex vivo human skin model. Toxicological Research. 2023;39(3):477–484. https://doi.org/10.1007/s43188-023-00185-1

17. Jaekel A., Wirtz M. Surface Characterization of Skin Substitute Materials. Skin Research & Technology. 2025;31(7):e70187. https://doi.org/10.1111/srt.70187

18. Jeong W. Y., Kwon M., Choi H. E., Kim K. S. Recent advances in transdermal drug delivery systems: a review. Biomaterials research. 2021;25(1):24. https://doi.org/10.1186/s40824-021-00226-6

19. Nguyen H. X., Nguyen C. N. Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals. Pharmaceutics. 2023;15(1):277. https://doi.org/10.3390/pharmaceutics15010277