BIOAVAILABILITY TESTING OF ASIATICOSIDE FROM ETHANOLIC EXTRACT OF PEGAGAN (Centela asiatica) LEAVES SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS (SNEDDS) IN WISTAR RATS (Ratus norvegicus)
DOI:
https://doi.org/10.36387/jiis.v11i2.3148Keywords:
Asiaticoside, Oral Bioavailability, Centella asiatica, Pharmacokinetics, HPLC, SNEDDSAbstract
Asiaticoside is a bioactive compound from Centella asiatica with limited oral bioavailability due to its poor aqueous solubility. This study aimed to evaluate the effect of a self-nanoemulsifying drug delivery system (SNEDDS) on the pharmacokinetic profile and oral bioavailability from ethanolic extract of of C. asiaticoside compared with conventional C. asiatica ethanolic extract. An HPLC method was validated for asiaticoside determination in rat serum based on selectivity, linearity, sensitivity, accuracy, and precision. Wistar rats were administered asiaticoside from ethanolic extract or SNEDDS orally, and blood samples were collected at predetermined intervals up to 360 minutes. Pharmacokinetic parameters including Cmax, Tmax, AUC₀–t, and relative bioavailability were subsequently determined. The HPLC method showed good linearity over 0.39–6.25 µg/mL with an R² of 0.9995 and acceptable accuracy and precision. SNEDDS increased the Cmax from 0.02362 ± 0.00207 to 0.15374 ± 0.00956 µg/mL and reduced Tmax from 240 to 120 minutes. The AUC₀–t increased from 5.22352 ± 0.16074 to 20.8248 ± 0.52093 µg·min/mL, resulting in 398.68% relative bioavailability, approximately 3.99-fold higher than the extract. The novelty of this study lies in demonstrating the substantial enhancement of asiaticoside absorption through SNEDDS. These findings provide a basis for developing nanoemulsion-based delivery systems to improve the oral delivery of poorly water-soluble bioactive compounds.
References
Anjelina, M., Renaldi, F., Shabira, K. K., & Febriyanti, S. T. (2025). In Silico Study of Secondary Metabolite in Asiatic Pennywort (Centella asiatica) as a Drug Compound for Blood Cancer (Acute Lymphoblastic Leukemia (ALL)) Targeting JAK-2 Receptor. 14(1). http://journal.unnes.ac.id/sju/index.php/ijcs
Annisa, R., Mutiah, R., Yuwono, M., & Hendradi, E. (2023). Nanotechnology Approach-Self Nanoemulsifying Drug Delivery System ( SNEDDS ). International Journal of Applied Pharmaceutics, 15(4), 12–19. https://doi.org/https://doi.org/10.22159/ijap.2023v15i4.47644
Anukunwithaya, T., Tantisira, M. H., Tantisira, B., & Khemawoot, P. (2017). Pharmacokinetics of a Standardized Extract of Centella asiatica ECa 233 in Rats. Planta Medica, 83(8), 710–717. https://doi.org/10.1055/s-0042-122344
Buya, A. B., Beloqui, A., & Memvanga, P. B. (2020). Self-Nano-Emulsifying Drug-Delivery Systems : From the Development to the Current Applications and Challenges in Oral Drug Delivery. 12(12), 1194. https://doi.org/https://doi.org/10.3390/pharmaceutics12121194
Chemical, C. (2022). Asiaticoside (Product Information Sheet, Item No. 11819). Cayman Chemical, 11819, 48108. https://cdn.caymanchem.com/cdn/insert/11819.pdf
Cherniakov, I., Domb, A. J., & Hoffman, A. (2015). Self-nano-emulsifying drug delivery systems: An update of the biopharmaceutical aspects. Expert Opinion on Drug Delivery, 12(7), 1121–1133. https://doi.org/10.1517/17425247.2015.999038
Fitrianda, E. K. A., Sukandar, E. Y., & Adnyana, I. K. (2017). Antidiabetic Activity Of Extract , Fractions , And Asiaticoside Compound Isolated From Centella Asiatica Linn . Leaves In Alloxan-Induced Diabetic Mice. Asian Journal of Pharmaceutical and Clinical Research, 10(10). https://doi.org/https://doi.org/10.22159/ajpcr.2017.v10i10.20419
Food and Drug Administration. (2018). Bioanalytical Method Validation Guidance for Industry. Bioanalytical Method Validation. https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf
Gray, N. E., Magana, A. A., Lak, P., Wright, K. M., Quinn, J., Stevens, J. F., Maier, C. S., & Soumyanath, A. (2018). Centella asiatica – Phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochemistry Reviews, 17(1), 161–194. https://doi.org/https://doi.org/10.1007/s11101-017-9528-y
ICH. (2022). M10 Bioanalytical Method Validation and Study Sample Analysis. November. https://database.ich.org/sites/default/files/M10_Guideline_Step4_2022_0524.pdf
Kazi, M., Al-Swairi, M., Ahmad, A., Raish, M., Alanazi, F. K., Badran, M. M., Khan, A. A., Alanazi, A. M., & Hussain, M. D. (2019). Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitroand in vivoAssessment. Frontiers in Pharmacology, 10(MAY), 1–13. https://doi.org/10.3389/fphar.2019.00459
KK, A. (2020). Centella asiatica (L.) urban: A review on panoramic exploration of medicinal marvels for health and healing. International Journal of Advanced Academic Studies, 2(1), 369–372. https://doi.org/https://www.doi.org/10.33545/27068919.2020.v2.i1f.1077
Lin, L., Chen, Q., Dai, Y., Xia, Y., Lin, L., Chen, Q., Dai, Y., & Xia, Y. (2023). Self-Nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Madecassic Acid : In vitro and in vivo Evaluation Self-Nanoemulsifying Drug Delivery System for Enhanced Bioavailability of Madecassic Acid : In vitro and in vivo Evaluation. International Journal of Nanomedicine, 9114. https://doi.org/10.2147/IJN.S408115
Madhusudhan, N. C., Neeraja, P., & Devi, P. (2014). Comparative Analysis of Active Constituents in Centella Asiatica Varieties (Majjaposhak and Subhodak). 4(2), 105–108. https://eijppr.com/tPReDEF
Melati, R., & Setiyadi, G. (2025). Formulasi Self-Nanoemulsifying Drug Delivery System (SNEDDS) dari Ekstrak Etanol Daun Pegagan (Centella asiatica) Sebagai Obat Antidiabetes Oral Pendahuluan. 2362–2371. https://doi.org/https://doi.org/10.36490/journal-jps.com
Sabillah, F. A., Fitriani, H., Zubair, M. S., & Syukri, Y. (2025). Self-Nanoemulsifying Drug Delivery System ( SNEDDS ): Challenges and Opportunities in Enhancing Drug Solubility. Jurnal Sains Farmasi & Klinis, 12(3), 217–225. https://doi.org/10.25077/jsfk.12.3.217-225.2025
Tawinwung, S., Junsaeng, D., Utthiya, S., & Khemawoot, P. (2021). Immunomodulatory effect of standardized C . asiatica extract on a promotion of regulatory T cells in rats. BMC Complementary Medicine and Therapies, 1–10. https://doi.org/https://doi.org/10.1186/s12906-021-03394-z
Wardiyah, Jufri, M., Mun, A., Zulfakar, M. H., & Sari, S. P. (2026). Stability and determination of asiaticoside from dry nanoemulsion in rat plasma by LC – MS / MS and its application in a pharmacokinetics study. Pharmacia, 73, 1–13. https://doi.org/10.3897/pharmacia.73.e176786
Wardiyah, Jufri, M., Sutriyo, Mun’im, A., & Zulfakar, M. H. (2024). Develpment And Optimization Of Asiaticoside Nanoemulsion Formulation By Box-Behnken Design. 72. https://doi.org/https://doi.org/10.31925/farmacia.2024.6.19
Wikantyasning, E. R., Setiyadi, G., Pramuningtyas, R., Dwi, M., & Ho, C. Y. E. E. (2023). Formulation of Nanoemulgel Containing Extract of Impatients Balsamina L. and Its Antibacterial Activity. International Journal of Applied Pharmaceutics, 15(3). https://doi.org/https://dx.doi.org/10.22159/ijap.2023v15i3.46670
Xing, L., Tan, Z., Cheng, J., Huang, W., Zhang, W., & Deng, W. (2017). Bioavailability and pharmacokinetic comparison of tanshinones between two formulations of Salvia miltiorrhiza in healthy volunteers. December 2016, 1–10. https://doi.org/10.1038/s41598-017-02747-4
Zhao, T., Maniglio, D., Chen, J., Chen, B., Motta, A., & Migliaresi, C. (2015). Design and optimization of self-nanoemulsifying formulations for lipophilic drugs. Nanotechnology, 26(12), 125102. https://doi.org/10.1088/0957-4484/26/12/125102
Downloads
Published
Issue
Section
License
Copyright (c) 2026 JIIS (Jurnal Ilmiah Ibnu Sina): Ilmu Farmasi dan Kesehatan
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
