Formulation, Optimization, and Characterization of Hepatoprotective Polyherbal Tablet

Abstract

Background: Liver cirrhosis is a liver disease with a high mortality rate worldwide, and antifibrotic drugs are generally used for alleviating symptoms, but there are still limitations of current therapies. Research is going on new therapies including herbals for management of cirrhosis.

Objective: Literature-based research identifies curcumin, hesperidin, Aegle marmelos (bael), Solanum nigrum (black nightshade), and Silybum marianum (milk thistle) as hepatoprotective phytoconstituents and herbs. The current study aims to develop and evaluate a hepatoprotective polyherbal tablet.

Methods: Tablets were prepared using the direct compression method utilizing polymers including microcrystalline cellulose, starch, etc. Response surface methodology (central composite design) was used for optimizing formulation, taking hardness and disintegration time as dependent variables. The prepared formulations were characterized using parameters including weight variation, friability, thickness, percentage drug release, etc. Furthermore, formulations were evaluated for release kinetics studies.

Results: Optimized formulation (F14) revealed percentage drug release from 71.57–94.91%. Furthermore, other parameters were also found to be satisfactory. Results from kinetics study revealed that F14 followed the Hinton-Crowell model with non-fickian release mechanism.

Conclusion: Polyherbal hepatoprotective tablets can be used for sustained delivery of polyherbs as an alternative therapy for management of liver cirrhosis and hepatoprotective action. Furthermore, pre-clinical and clinical studies should be done for better applicability.

  • Page Number : 105-118
  • Published Date : 2025-12-20
  • Keywords
    Liver cirrhosis, Hepatoprotective, Tablet, Herbs, Phytochemicals, Controlled release
  • DOI Number
    10.15415/jptrm.2025.131008
  • Authors
    Kamaljeet1, Rameshwar Das, Priyanka Kriplani, and Prabhjot Kaur

References

  • Aghazadeh, S., Amini, R., Yazdanparast, R., & Ghaffari, S. H. (2011). Anti-apoptotic and anti-inflammatory effects of Silybum marianum in treatment of experimental steatohepatitis. Experimental and toxicologic pathology63(6), 569-574.
  • Ahmad, W., Amir, M., Ahmad, A., Ali, A., Ali, A., Wahab, S., Barkat, H.A., Ansari, M.A., Sarafroz, M., Ahmad, A. & Alam, P. (2021). Aegle marmelos leaf extract phytochemical analysis, cytotoxicity, in vitro antioxidant and antidiabetic activities. Plants10(12), 2573.
  • Bhardwaj, R. L., & Nandal, U. (2015). Nutritional and therapeutic potential of bael (Aegle marmelos Corr.) fruit juice: a review. Nutrition & Food Science45(6), 895-919.
  • Chimagave, S. S., Jalalpure, S. S., Patil, A. K., & Kurangi, B. K. (2022). Development and validation of stability indicating UV-spectrophotometric method for the estimation of hesperidin in bulk drugs, plant extract, Ayurveda formulation and nanoformulation. Indian J Pharm Educ Res56(3), 865-872.
  • Cofano, M., Saponara, I., De Nunzio, V., Pinto, G., Aloisio Caruso, E., Centonze, M., & Notarnicola, M. (2025). Hesperidin Is a Promising Nutraceutical Compound in Counteracting the Progression of NAFLD In Vitro. International Journal of Molecular Sciences26(13), 5982.
  • Devarbhavi, H., Asrani, S. K., Arab, J. P., Nartey, Y. A., Pose, E., & Kamath, P. S. (2023). Global burden of liver disease: 2023 update. Journal of hepatology79(2), 516-537.
  • Ekenna, I. C., & Abali, S. O. (2022). Comparison of the use of kinetic model plots and DD solver software to evaluate the drug release from griseofulvin tablets. Jornal of Drug Delivery Ther12(2-S), 5-13.
  • Federico, A., Dallio, M., & Loguercio, C. (2017). Silymarin/silybin and chronic liver disease: a marriage of many years. Molecules22(2), 191.
  • Gupta, A., Thomas, T., & Khan, S. (2018). Physicochemical, phytochemical screening and antimicrobial activity of Aegle marmelos. Pharmaceutical and Biosciences Journal, 17-24.
  • Jiang, G., Sun, C., Wang, X., Mei, J., Li, C., Zhan, H., Liao, Y., Zhu, Y.  & Mao, J. (2022). Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered13(3), 5216-5235.
  • Khonche, A., Huseini, H. F., Gholamian, M., Mohtashami, R., Nabati, F., & Kianbakht, S. (2019). Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: A randomized, double-blind and placebo-controlled clinical trial. Journal of Ethnopharmacology234, 106-111.
  • Kornerup, L. S., Kraglund, F., Askgaard, G., Vilstrup, H., & Jepsen, P. (2025). Cirrhosis epidemiology in Denmark 1998–2022, and 2030 forecast. JHEP Reports7(5).
  • Li, X., Yao, Y., Wang, Y., Hua, L., Wu, M., Chen, F., Deng, Z.Y.& Luo, T. (2022). Effect of hesperidin supplementation on liver metabolomics and gut microbiota in a high-fat diet-induced NAFLD mice model. Journal of Agricultural and Food Chemistry70(36), 11224-11235.
  • Liew, K. B., & Peh, K. K. (2021). Investigation on the effect of polymer and starch on the tablet properties of lyophilized orally disintegrating tablet. Archives of pharmacal research44(8), 1-10.
  • Loke, Y.H., Phang, H.C., Gobal, G., Vijayaraj Kumar, P., Kee, P.E., Widodo, R.T., Goh, B.H.& Liew, K. B. (2024). Application of cocoa butter for formulation of fast melt tablets containing memantine hydrochloride. Drug Development and Industrial Pharmacy50(10), 845-855.
  • Lukic, I., Milovanovic, S., Pantic, M., Srbljak, I., Djuric, A., Tadic, V., & Tyśkiewicz, K. (2022). Separation of high-value extracts from Silybum marianum seeds: Influence of extraction technique and storage on composition and bioactivity. Lwt160.
  • Majumder, K. K., Sharma, J. B., Kumar, M., Bhatt, S., & Saini, V. (2020). Development and validation of UV-Visible spectrophotometric method for the estimation of curcumin in bulk and pharmaceutical formulation‎‎. Pharmacophore11(1-2020), 115-121.
  • Mancak, M., Altintas, D., Balaban, Y., & Caliskan, U. K. (2024). Evidence-based herbal treatments in liver diseases. In Hepatology forum, 5(1), 50.
  • Mirhafez, S.R., Azimi-Nezhad, M., Dehabeh, M., Hariri, M., Naderan, R.D., Movahedi, A., Abdalla, M., Sathyapalan, T. & Sahebkar, A. (2021). The effect of curcumin phytosome on the treatment of patients with non-alcoholic fatty liver disease: a double-blind, randomized, placebo-controlled trial. In Pharmacological properties of plant-derived natural products and implications for human health, 25-35.
  • Morshedzadeh, N., Ramezani Ahmadi, A., Behrouz, V., & Mir, E. (2023). A narrative review on the role of hesperidin on metabolic parameters, liver enzymes, and inflammatory markers in nonalcoholic fatty liver disease. Food Science & Nutrition11(12), 7523-7533.
  • Morteza-Semnani, K., Saeedi, M., Akbari, J., Hedayati, S., Hashemi, S.M.H., Rahimnia, S.M., Babaei, A., Ghazanfari, M., Haghani, I. & Hedayati, M. T. (2022). Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method. Journal of Biomaterials Science, Polymer Edition33(18), 2325-2352.
  • Mukhtar, S., Xiaoxiong, Z., Khalid, W., Moreno, A., & Lorenzo, J. M. (2023). In vitro antioxidant capacity of purified bioactive compounds in Milk thistle seed (Silybum marianum) along with phenolic profile. Food Analytical Methods16(4), 651-663.
  • Musuc, A.M., Anuta, V., Atkinson, I., Sarbu, I., Popa, V.T., Munteanu, C., Mircioiu, C., Ozon, E.A., Nitulescu, G.M. & Mitu, M. A. (2021). Formulation of chewable tablets containing carbamazepine-β-cyclodextrin inclusion complex and f-melt disintegration excipient. The mathematical modeling of the release kinetics of carbamazepine. Pharmaceutics13(6), 915.
  • Narukulla, S., Bogadi, S., Tallapaneni, V., Sanapalli, B.K.R., Sanju, S., Khan, A.A., Malik, A., Barai, H.R., Mondal, T.K., Karri, V.V.S.R. & Papadakis, M. (2024). Comparative study between the Full Factorial, Box–Behnken, and Central Composite Designs in the optimization of metronidazole immediate release tablet. Microchemical Journal207.
  • Ngu, M. H., Norhayati, M. N., Rosnani, Z., & Zulkifli, M. M. (2022). Curcumin as adjuvant treatment in patients with non-alcoholic fatty liver (NAFLD) disease: A systematic review and meta-analysis. Complementary Therapies in Medicine68.
  • Panchal, P. M., & Shah, D. A. (2025). Simultaneous quantification of quercetin and solasodine biomarkers from Solanum nigrum Linn. berry extract using a validated high-performance thin-layer chromatography‒densitometric method. JPC–Journal of Planar Chromatography–Modern TLC, 1-11.
  • Park, M.N., Rahman, M.A., Rahman, M.H., Kim, J.W., Choi, M., Kim, J.W., Choi, J., Moon, M., Ahmed, K.R.& Kim, B. (2022). Potential therapeutic implication of herbal medicine in mitochondria-mediated oxidative stress-related liver diseases. Antioxidants11(10), 2041.
  • Ravikkumar, V.R., Patel, B.D., Rathi, S., Parthiban, S., Upadhye, M.C., Shah, A.M., Rehan, S.S.A., Samanta, S. & Singh, S. (2024). Formulation and evaluation of Drumstick leaves tablet as an immunomodulator. Zhongguo Ying Yong Sheng Li Xue Za Zhi40.
  • Robinson, K., Mock, C., & Liang, D. (2015). Pre-formulation studies of resveratrol. Drug development and industrial pharmacy41(9), 1464-1469.
  • Różański, G., Kujawski, S., Newton, J. L., Zalewski, P., & Słomko, J. (2021). Curcumin and biochemical parameters in metabolic-associated fatty liver disease (MAFLD)—A review. Nutrients13(8), 2654.
  • Shahrebabak, M. G., Haghighi, S. P. S., Ravankhah, M., Zare, A., Bazyari, V., & Izadi, B. (2025). A Systematic Review and Meta-analysis of Randomised Controlled Trials on Curcumin-Piperine Supplementation: A Promising Strategy for Managing Lipid Profiles and Liver Health in Non-alcoholic Fatty Liver Disease. Journal of Herbal Medicine51.
  • Shaker, E., Mahmoud, H., & Mnaa, S. (2010). Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food and Chemical Toxicology48(3), 803-806.
  • Sharma, R., Bansal, M., Garg, A., Agarwal, V., & Sharma, D. (2023). Formulation and Evaluation of Sustain Release Matrix Tablet of Aceclofenac. International Journal of Health Advancement and Clinical Research (tz)1(1).
  • Singanan, V., Singanan, M., & Begum, H. (2007). The hepatoprotective effect of bael leaves (Aegle marmelos) in alcohol induced liver injury in albino rats. International Journal of Science & Technology2(2), 83-92.
  • Sivaslioglu, A., & Goktas, Z. (2024). A comprehensive review on the impact of hesperidin and its aglycone hesperetin on metabolic dysfunction-associated steatotic liver disease and other liver disorders. Nutrition research reviews, 1-37.
  • Solati, Z., Baharin, B. S., & Bagheri, H. (2014). Antioxidant property, thymoquinone content and chemical characteristics of different extracts from Nigella sativa L. seeds. Journal of the American Oil Chemists' Society91(2), 295-300.
  • Tafere, C., Yilma, Z., Abrha, S., & Yehualaw, A. (2021). Formulation, in vitro characterization and optimization of taste-masked orally disintegrating co-trimoxazole tablet by direct compression. PloS one16(3).
  • Tang, G., Zhang, L., Tao, J., & Wei, Z. (2021). Effect of Nigella sativa in the treatment of nonalcoholic fatty liver disease: A systematic review and meta‐analysis of randomized controlled trials. Phytotherapy Research35(8), 4183-4193.
  • Terrault, N. A., Francoz, C., Berenguer, M., Charlton, M., & Heimbach, J. (2023). Liver transplantation 2023: status report, current and future challenges. Clinical Gastroenterology and Hepatology21(8), 2150-2166.
  • Tiwari, A., Surendra, G., Meka, S., Varghese, B., Vishwakarma, G., & Adela, R. (2022). The effect of Nigella sativa on non-alcoholic fatty liver disease: A systematic review and meta-analysis. Human Nutrition & Metabolism28, 200146.
  • Venkatesh, D.N., Meyyanathan, S.N., Kovacevic, A., Zielińska, A., Fonseca, J., Eder, P., Dobrowolska, A. & Souto, E. B. (2022). Effect of hydrophilic polymers on the release rate and pharmacokinetics of acyclovir tablets obtained by wet granulation: in vitro and in vivo assays. Molecules27(19).
  • Vlizlo, V., Prystupa, O., Slivinska, L., Gutyj, B., Maksymovych, I., Shcherbatyy, A., Lychuk, M., Partyka, U., Chernushkin, B., Rusyn, V. & Leskiv, K. (2023). Treatment of animals with fatty liver disease using a drug based on the seeds of Silybum marianum. Regulatory Mechanisms in Biosystems14(3), 424-431.
  • Yari, Z., Cheraghpour, M., Alavian, S. M., Hedayati, M., Eini-Zinab, H., & Hekmatdoost, A. (2021). The efficacy of flaxseed and hesperidin on non-alcoholic fatty liver disease: an open-labeled randomized controlled trial. European journal of clinical nutrition75(1), 99-111.
  • Zhang, C., Shao, H., Han, Z., Liu, B., Feng, J., Zhang, J., Zhang, W., Zhang, K., Yang, Q. & Wu, S. (2023). Development and in vitro–in vivo correlation evaluation of IMM-H014 extended-release tablets for the treatment of fatty liver disease. International Journal of Molecular Sciences24(15), 12328.
  • Zhao, H., Shi, C., Zhao, L., Wang, Y., & Shen, L. (2022). Influences of different microcrystalline cellulose (MCC) grades on tablet quality and compression behavior of MCC-lactose binary mixtures. Journal of Drug Delivery Science and Technology77.