Optimization of pH-Responsive Polymer Gel Combination of Green Tea and Temulawak Extracts Using a Design of Experiments (DoE) Approach
Abstract
Background: Inflammation is a significant global health issue, often treated with topical therapies. The combination of green tea (Camellia sinensis) and temulawak (Curcuma xanthorrhiza) offers potential as a natural anti-inflammatory alternative due to their rich content of catechins and curcuminoids. A pH-responsive polymer gel base can enhance stability and provide controlled release of active compounds at the inflammation site.
Objective: To optimize and characterize a pH-responsive polymer gel containing both extracts using a Design of Experiments (DoE) mixture approach.
Methods: Ethanolic extracts (96%) of both plants were obtained by maceration. Five gel formulas (F1-F5) were formulated using a mixture design with varying ratios of sodium alginate (1-2.5%) and tragacanth gum (0.5-2%). The physical properties of the gels, including organoleptic characteristics, homogeneity, pH, viscosity, and spreadability, were evaluated.
Results: Phytochemical screening confirmed the presence of alkaloids, flavonoids, and tannins in both extracts. All gel formulas had a pH of ~5, ideal for skin application. Viscosity exceeded 2500 dPas for all formulas, and DoE analysis identified gum tragacanth as the dominant factor influencing viscosity. Spreadability ranged from 6.12 to 7.88 cm. Formula F5 demonstrated the most favorable overall characteristics, with the highest viscosity and best spreadability. A key challenge was the inhomogeneity observed in all formulas.
Conclusion: A pH-responsive polymer gel was successfully developed using a data-driven DoE approach. Formula F5 was the optimal candidate, demonstrating superior physical properties as a promising natural anti-inflammatory topical agent, pending further optimization for homogeneity.
References
1. Latifah, L., & Rahman, F. (2024). Formulasi, Karakterisasi Fisik dan Uji Pelepasan Patch Tipe Membran yang Mengandung Sediaan Krim Natrium Diklofenak sebagai Reservoir. Jurnal Farmamedika (Pharmamedika Journal), 9(2), 203-210. https://doi.org/10.47219/ath.v9i2.39
2. Wahdah, A. S., Windarti, I. ., Setyaningrum, E., & Sukohar, A. (2025). Article Review: Risk of Lung Cancer in Patients with History of Pulmonary Tuberculosis and Chronic Obstructive Pulmonary Disease (COPD). Medical Profession Journal of Lampung, 14(9), 1845-1850. https://doi.org/10.53089/medula.v14i9.1344
3. Fahmi, F. N. A. (2023). A Anti-Inflammatory Effect of Matoa Leaf Ethanol Extract (Pometia Pinnata Jr Forst & G. Forst) in Male Rats (Rattus norvegicus). Makassar Natural Product Journal (MNPJ), 33-43. https://doi.org/10.33096/mnpj.v1i2.20
4. Nurtanti, D., & Tejamaya, M. (2023). Analisis Faktor Risiko Gangguan Muskuloskeletal Pada Pekerja Kantor: Sebuah Tinjauan Pustaka. Jurnal Kesehatan Tambusai, 4(2), 2414-2424. https://doi.org/10.31004/jkt.v4i2.15780
5. Soleha, M., Isnawati, A., Fitri, N., Adelina, R., Soblia, H. T., & Winarsih, W. (2018). Profil penggunaan obat antiinflamasi nonstreoid di Indonesia. Jurnal Kefarmasian Indonesia, 109-117. https://doi.org/10.22435/jki.v8i2.316
6. Sasmita, E., Salam, A. Y., & Sriyono, G. H. (2023). Efektifitas Knee Pain Exercise Dan Kompres Hangat Terhadap Nyeri Osteoarthritis Lutut Di Desa Mojolegi Kecamatan Gading Kabupaten Probolingg0. JURNAL RISET RUMPUN ILMU KESEHATAN, 2(2), 168-180. https://doi.org/10.55606/jurrikes.v2i2.1752
7. Latifah, L., Hendradi, E., & Isadiartuti, D. (2024). Effect ratio of stearic acid and oleic acid on characteristics of diclofenac sodium nanostructured lipid carrier. Pharmacy Education, 24(3), p. 336–342. https://doi.org/10.46542/pe.2024.243.336342
8. Dewi, Y. K., & Riyandari, B. A. (2020). Potensi tanaman lokal sebagai tanaman obat dalam menghambat penyebaran Covid-19. Jurnal Pharmascience, 7(2), 112-128. http://dx.doi.org/10.20527/jps.v7i2.8793
9. Nurcholis, W. (2023). Uji Toksisitas Tiga Varietas Temulawak (Curcuma xanthorrhiza Roxb) sebagai Kandidat Antikanker dengan Metode BSLT (Brine Shrimp Lethality Test). Agrin, 27(1), 1-11. https://doi.org/10.20884/1.agrin.2023.27.1.728
10. Riendra, M., Lipoeto, N. I., Rita, R. S., & Basyar, M. (2024). Peran Epigallocatechin-3-gallate (EGCG) dalam Menghambat Perkembangan Fibrosis Pleura, Ekspresi SCUBE3, dan Transforming Growth Factror-β (TGF-β) pada Pasien Empiema: sebuah tinjauan pustaka. Intisari Sains Medis, 15(1), 495-500. https://doi.org/10.15562/ism.v15i1.2001
11. Syamsi, L. N., Syamsudin, S., Mumpuni, E., Widowati, W., Nursanti, O., & Qodriah, R. (2025). Analisis In Silico Senyawa Curcuma xanthorrhiza dan Moringa oleifera sebagai Kandidat Antiinflamasi. Journal Syifa Sciences and Clinical Research (JSSCR), 7(1). https://doi.org/10.37311/jsscr.v7i1.30385
12. Ullah, F., Iqbal, Z., Khan, A., Khan, S. A., Ahmad, L., Alotaibi, A., Ullah, R., & Shafique, M. (2022). Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate). Frontiers in pharmacology, 13, 911771. https://doi.org/10.3389/fphar.2022.911771
13. Nugroho, A. A., Adianto, C., & Patria, Y. (2020). Nano-Androcerum: Inovasi wound healinggel dari nanopartikel daun binahong dan kayu manis pada luka kronis. Berkala Ilmiah Mahasiswa Farmasi Indonesia, 7(1), 026-042. https://doi.org/10.48177/bimfi.v7i1.11
14. Nining, N., Fith Khaira Nursal, & Abu Rijal Algifari. (2023). Kinetics of Piroxicam Release through Iontophoresis at Various PHS from Polyelectrolyte Hydrogels with Sodium Alginate-Tragacanth Gum Polymer. Jurnal Farmasimed (JFM), 6(1), 51–58. https://doi.org/10.35451/jfm.v6i1.1904
15. Irianto, I. D. K., Purwanto, P., & Mardan, M. T. (2020). Aktivitas antibakteri dan uji sifat fisik sediaan gel dekokta sirih hijau (Piper betle L.) sebagai alternatif pengobatan mastitis sapi. Majalah Farmaseutik, 16(2), 202-210. https://doi.org/10.22146/farmaseutik.v16i2.53793
16. Allen, L., & Ansel, H. C. (2013). Ansel's pharmaceutical dosage forms and drug delivery systems. Lippincott Williams & Wilkins.
17. Yusuf, A. L., Nurawaliah, E., & Harun, N. (2017). Uji efektivitas gel ekstrak etanol daun kelor (Moringa oleifera L.) sebagai antijamur Malassezia furfur. Kartika: Jurnal Ilmiah Farmasi, 5(2), 62-67. https://doi.org/10.26874/kjif.v5i2.119
18. Kim, M.J., Yang, Y.J., Min, GY. et al. Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition. Sci Rep 15, 2371 (2025). https://doi.org/10.1038/s41598-025-86678-5
19. Kim, S., Kook, K. E., Kim, C., & Hwang, J. K. (2018). Inhibitory effects of Curcuma xanthorrhiza supercritical extract and xanthorrhizol on LPS-induced inflammation in HGF-1 cells and RANKL-induced osteoclastogenesis in RAW264. 7 cells. Journal of microbiology and biotechnology, 28(8), 1270-1281. https://doi.org/10.4014/jmb.1803.03045
20. Kim, M. J., Yang, Y. J., Min, G. Y., Heo, J. W., Son, J. D., You, Y. Z., ... & Park, K. I. (2025). Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition. Scientific Reports, 15(1), 2371. https://doi.org/10.1038/s41598-025-86678-5
21. Patel, R. P., et al. (2020). Formulation and Evaluation of Topical Gel: A Comprehensive Review. Journal of Drug Delivery and Therapeutics, *10*(4-s), 174-181. https://doi.org/10.22270/jddt.v10i4-s.4184
22. Sharma, A., et al. (2022). Optimization and Characterization of Topical Gel Formulation: A Systematic Approach. Journal of Pharmaceutical Innovation, 17(3), 567-578. https://doi.org/10.1007/s12247-021-09535-8
23. Kusuma, T. M., Azalea, M., Dianita, P., & Syifa, N. (2018). Pengaruh variasi jenis dan konsentrasi gelling agent terhadap sifat fisik gel hidrokortison. Jurnal Farmasi Sains dan Praktis, 44-49. https://doi.org/10.31603/pharmacy.v4i1.2589
24. Yusuf, A. L., Nugraha, D., Wahlanto, P., Indriastuti, M., Ismail, R., & Himah, F. A. (2022). Formulasi Dan Evaluasi Sediaan Gel Ekstrak Buah Pare (Momordica Charantia L.) Dengan Variasi Konsentrasi Carbopol 940. Pharmacy Genius, 1(1), 50-61. https://doi.org/10.56359/pharmgen.v1i01.149
25. Thomas, N. A., Tungadi, R., Hiola, F., & Latif, M. S. (2023). Pengaruh konsentrasi carbopol 940 sebagai gelling agent terhadap stabilitas fisik sediaan gel lidah buaya (Aloe Vera). Indonesian Journal of Pharmaceutical Education, 3(2). https://doi.org/10.37311/ijpe.v3i2.18050
26. Alfian, M., Hasanudin, M. N., & Mujib, M. F. (2022). Uji sifat fisik sediaan gel ekstrak etanol daun kitolod. JIFS: Jurnal Ilmiah Farmasi Simplisia, 2(1), 1-7.
2. Wahdah, A. S., Windarti, I. ., Setyaningrum, E., & Sukohar, A. (2025). Article Review: Risk of Lung Cancer in Patients with History of Pulmonary Tuberculosis and Chronic Obstructive Pulmonary Disease (COPD). Medical Profession Journal of Lampung, 14(9), 1845-1850. https://doi.org/10.53089/medula.v14i9.1344
3. Fahmi, F. N. A. (2023). A Anti-Inflammatory Effect of Matoa Leaf Ethanol Extract (Pometia Pinnata Jr Forst & G. Forst) in Male Rats (Rattus norvegicus). Makassar Natural Product Journal (MNPJ), 33-43. https://doi.org/10.33096/mnpj.v1i2.20
4. Nurtanti, D., & Tejamaya, M. (2023). Analisis Faktor Risiko Gangguan Muskuloskeletal Pada Pekerja Kantor: Sebuah Tinjauan Pustaka. Jurnal Kesehatan Tambusai, 4(2), 2414-2424. https://doi.org/10.31004/jkt.v4i2.15780
5. Soleha, M., Isnawati, A., Fitri, N., Adelina, R., Soblia, H. T., & Winarsih, W. (2018). Profil penggunaan obat antiinflamasi nonstreoid di Indonesia. Jurnal Kefarmasian Indonesia, 109-117. https://doi.org/10.22435/jki.v8i2.316
6. Sasmita, E., Salam, A. Y., & Sriyono, G. H. (2023). Efektifitas Knee Pain Exercise Dan Kompres Hangat Terhadap Nyeri Osteoarthritis Lutut Di Desa Mojolegi Kecamatan Gading Kabupaten Probolingg0. JURNAL RISET RUMPUN ILMU KESEHATAN, 2(2), 168-180. https://doi.org/10.55606/jurrikes.v2i2.1752
7. Latifah, L., Hendradi, E., & Isadiartuti, D. (2024). Effect ratio of stearic acid and oleic acid on characteristics of diclofenac sodium nanostructured lipid carrier. Pharmacy Education, 24(3), p. 336–342. https://doi.org/10.46542/pe.2024.243.336342
8. Dewi, Y. K., & Riyandari, B. A. (2020). Potensi tanaman lokal sebagai tanaman obat dalam menghambat penyebaran Covid-19. Jurnal Pharmascience, 7(2), 112-128. http://dx.doi.org/10.20527/jps.v7i2.8793
9. Nurcholis, W. (2023). Uji Toksisitas Tiga Varietas Temulawak (Curcuma xanthorrhiza Roxb) sebagai Kandidat Antikanker dengan Metode BSLT (Brine Shrimp Lethality Test). Agrin, 27(1), 1-11. https://doi.org/10.20884/1.agrin.2023.27.1.728
10. Riendra, M., Lipoeto, N. I., Rita, R. S., & Basyar, M. (2024). Peran Epigallocatechin-3-gallate (EGCG) dalam Menghambat Perkembangan Fibrosis Pleura, Ekspresi SCUBE3, dan Transforming Growth Factror-β (TGF-β) pada Pasien Empiema: sebuah tinjauan pustaka. Intisari Sains Medis, 15(1), 495-500. https://doi.org/10.15562/ism.v15i1.2001
11. Syamsi, L. N., Syamsudin, S., Mumpuni, E., Widowati, W., Nursanti, O., & Qodriah, R. (2025). Analisis In Silico Senyawa Curcuma xanthorrhiza dan Moringa oleifera sebagai Kandidat Antiinflamasi. Journal Syifa Sciences and Clinical Research (JSSCR), 7(1). https://doi.org/10.37311/jsscr.v7i1.30385
12. Ullah, F., Iqbal, Z., Khan, A., Khan, S. A., Ahmad, L., Alotaibi, A., Ullah, R., & Shafique, M. (2022). Formulation Development and Characterization of pH Responsive Polymeric Nano-Pharmaceuticals for Targeted Delivery of Anti-Cancer Drug (Methotrexate). Frontiers in pharmacology, 13, 911771. https://doi.org/10.3389/fphar.2022.911771
13. Nugroho, A. A., Adianto, C., & Patria, Y. (2020). Nano-Androcerum: Inovasi wound healinggel dari nanopartikel daun binahong dan kayu manis pada luka kronis. Berkala Ilmiah Mahasiswa Farmasi Indonesia, 7(1), 026-042. https://doi.org/10.48177/bimfi.v7i1.11
14. Nining, N., Fith Khaira Nursal, & Abu Rijal Algifari. (2023). Kinetics of Piroxicam Release through Iontophoresis at Various PHS from Polyelectrolyte Hydrogels with Sodium Alginate-Tragacanth Gum Polymer. Jurnal Farmasimed (JFM), 6(1), 51–58. https://doi.org/10.35451/jfm.v6i1.1904
15. Irianto, I. D. K., Purwanto, P., & Mardan, M. T. (2020). Aktivitas antibakteri dan uji sifat fisik sediaan gel dekokta sirih hijau (Piper betle L.) sebagai alternatif pengobatan mastitis sapi. Majalah Farmaseutik, 16(2), 202-210. https://doi.org/10.22146/farmaseutik.v16i2.53793
16. Allen, L., & Ansel, H. C. (2013). Ansel's pharmaceutical dosage forms and drug delivery systems. Lippincott Williams & Wilkins.
17. Yusuf, A. L., Nurawaliah, E., & Harun, N. (2017). Uji efektivitas gel ekstrak etanol daun kelor (Moringa oleifera L.) sebagai antijamur Malassezia furfur. Kartika: Jurnal Ilmiah Farmasi, 5(2), 62-67. https://doi.org/10.26874/kjif.v5i2.119
18. Kim, M.J., Yang, Y.J., Min, GY. et al. Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition. Sci Rep 15, 2371 (2025). https://doi.org/10.1038/s41598-025-86678-5
19. Kim, S., Kook, K. E., Kim, C., & Hwang, J. K. (2018). Inhibitory effects of Curcuma xanthorrhiza supercritical extract and xanthorrhizol on LPS-induced inflammation in HGF-1 cells and RANKL-induced osteoclastogenesis in RAW264. 7 cells. Journal of microbiology and biotechnology, 28(8), 1270-1281. https://doi.org/10.4014/jmb.1803.03045
20. Kim, M. J., Yang, Y. J., Min, G. Y., Heo, J. W., Son, J. D., You, Y. Z., ... & Park, K. I. (2025). Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition. Scientific Reports, 15(1), 2371. https://doi.org/10.1038/s41598-025-86678-5
21. Patel, R. P., et al. (2020). Formulation and Evaluation of Topical Gel: A Comprehensive Review. Journal of Drug Delivery and Therapeutics, *10*(4-s), 174-181. https://doi.org/10.22270/jddt.v10i4-s.4184
22. Sharma, A., et al. (2022). Optimization and Characterization of Topical Gel Formulation: A Systematic Approach. Journal of Pharmaceutical Innovation, 17(3), 567-578. https://doi.org/10.1007/s12247-021-09535-8
23. Kusuma, T. M., Azalea, M., Dianita, P., & Syifa, N. (2018). Pengaruh variasi jenis dan konsentrasi gelling agent terhadap sifat fisik gel hidrokortison. Jurnal Farmasi Sains dan Praktis, 44-49. https://doi.org/10.31603/pharmacy.v4i1.2589
24. Yusuf, A. L., Nugraha, D., Wahlanto, P., Indriastuti, M., Ismail, R., & Himah, F. A. (2022). Formulasi Dan Evaluasi Sediaan Gel Ekstrak Buah Pare (Momordica Charantia L.) Dengan Variasi Konsentrasi Carbopol 940. Pharmacy Genius, 1(1), 50-61. https://doi.org/10.56359/pharmgen.v1i01.149
25. Thomas, N. A., Tungadi, R., Hiola, F., & Latif, M. S. (2023). Pengaruh konsentrasi carbopol 940 sebagai gelling agent terhadap stabilitas fisik sediaan gel lidah buaya (Aloe Vera). Indonesian Journal of Pharmaceutical Education, 3(2). https://doi.org/10.37311/ijpe.v3i2.18050
26. Alfian, M., Hasanudin, M. N., & Mujib, M. F. (2022). Uji sifat fisik sediaan gel ekstrak etanol daun kitolod. JIFS: Jurnal Ilmiah Farmasi Simplisia, 2(1), 1-7.
Published
2026-08-21
How to Cite
LATIFAH, Luluk; FATMAWATI, Umi.
Optimization of pH-Responsive Polymer Gel Combination of Green Tea and Temulawak Extracts Using a Design of Experiments (DoE) Approach.
Acta Pharmaciae Indonesia : Acta Pharm Indo, [S.l.], v. 14, n. 1, p. 18293, aug. 2026.
ISSN 2621-4520.
Available at: <https://jos.unsoed.ac.id/index.php/api/article/view/18293>. Date accessed: 27 aug. 2026.
doi: https://doi.org/10.20884/1.api.2026.14.1.18293.
Section
Articles
This work is licensed under a Creative Commons Attribution 4.0 International License.
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