Compartmental Kinetic Modeling of In Vitro Transdermal Permeation Across Strat-M® Membranes: A Case of Andrographis paniculata Extract Nanoemulsion
DOI:
https://doi.org/10.22146/ijp.29693Keywords:
andrographolide, compartmental modeling, nanoemulsion, permeation kinetics, strat-mAbstract
Andrographolide (AND), the main bioactive compound of Andrographis paniculata, exhibits various pharmacological activities but has limited therapeutic application due to its low oral bioavailability. Transdermal drug delivery system (TDDS) may provide an alternative route to improve systemic exposure while avoiding first-pass metabolism. However, information regarding the kinetic behavior of AND from herbal crude extract systems in transdermal formulations is still limited. This study evaluated the in vitro permeation of AND from Andrographis paniculata extract (APE) nanoemulsion across Strat-M® membranes and characterized its transport kinetics using compartmental modeling. Permeation testing was conducted for 24 hours using an Automated Diffusion Cell System, and AND concentrations in the receptor medium were quantified by HPLC. The cumulative amount of AND permeated after 24 hours was 132.6 ± 2.2 µg (mean ± SD, n = 3), indicating good reproducibility of the experimental system. The permeation data were analyzed using several compartmental models in WinSAAM. A four-compartment model with two lag compartments arranged in parallel configuration provided the best fit to the observed data. The model indicated transient retention of AND within membrane layers analogous to the stratum corneum and viable epidermis prior to transfer into the receptor phase. The estimated transport parameters suggested relatively faster mass transfer from the membrane to the receptor compartment, while the low aqueous solubility of AND contributes to diffusion limitations in more hydrophilic regions. These results provide quantitative insight into the permeation mechanism of AND from nanoemulsion systems and may support the rational development of transdermal formulations for herbal extracts.
References
Adiguna, S. P., Panggabean, J. A., Swasono, R. T., Rahmawati, S. I., Izzati, F., Bayu, A., Putra, M. Y., Formisano, C., & Giuseppina, C. (2023). Evaluations of Andrographolide-Rich Fractions of Andrographis paniculata with Enhanced Potential Antioxidant, Anticancer, Antihypertensive, and Anti-Inflammatory Activities. Plants, 12(6), 1220. https://doi.org/10.3390/plants12061220
Amarah, A. A., Petlin, D. G., Grice, J. E., Hadgraft, J., Roberts, M. S., & Anissimov, Y. G. (2018). Compartmental modeling of skin transport. European Journal of Pharmaceutics and Biopharmaceutics, 130, 336–344. https://doi.org/10.1016/j.ejpb.2018.07.015
Anissimov, Y. G., Jepps, O. G., Dancik, Y., & Roberts, M. S. (2013). Mathematical and pharmacokinetic modelling of epidermal and dermal transport processes. Advanced Drug Delivery Reviews, 65(2), 169–190. https://doi.org/10.1016/j.addr.2012.04.009
Dai, Y., Chen, S.-R., Chai, L., Zhao, J., Wang, Y., & Wang, Y. (2019). Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Critical Reviews in Food Science and Nutrition, 59(sup1), S17–S29. https://doi.org/10.1080/10408398.2018.1501657
Green, M. H., & Green, J. B. (2022). The Use of Datasets for Theoretical Subjects to Validate Vitamin A–Related Methods and Experimental Designs. The Journal of Nutrition, 152(3), 707–713. https://doi.org/10.1093/jn/nxab441
Haq, A., Dorrani, M., Goodyear, B., Joshi, V., & Michniak-Kohn, B. (2018). Membrane properties for permeability testing: Skin versus synthetic membranes. International Journal of Pharmaceutics, 539(1–2), 58–64. https://doi.org/10.1016/j.ijpharm.2018.01.029
Kaur, L., Singh, K., Paul, S., Singh, S., Singh, S., & Jain, S. K. (2018). A Mechanistic Study to Determine the Structural Similarities Between Artificial Membrane Strat-MTM and Biological Membranes and Its Application to Carry Out Skin Permeation Study of Amphotericin B Nanoformulations. AAPS PharmSciTech, 19(4), 1606–1624. https://doi.org/10.1208/s12249-018-0959-6
Kaushik, S., Dar, L., Kaushik, S., & Yadav, J. P. (2021). Identification and characterization of new potent inhibitors of dengue virus NS5 proteinase from Andrographis paniculata supercritical extracts on in animal cell culture and in silico approaches. Journal of Ethnopharmacology, 267, 113541. https://doi.org/10.1016/j.jep.2020.113541
Kunita, R., Nishijima, T., Todo, H., Sugibayashi, K., & Sakaguchi, H. (2022). A Mathematical Approach Using Strat-M® to Predict the Percutaneous Absorption of Chemicals under Finite Dose Conditions. Pharmaceutics, 14(7), 1370. https://doi.org/10.3390/pharmaceutics14071370
Martihandini, N., Surini, S., & Bahtiar, A. (2021). Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study. Pharmaceutical Sciences, 1. https://doi.org/10.34172/PS.2021.76
Naito, C., Yamaguchi, T., Katsumi, H., Kimura, S., Kamei, S., Morishita, M., Sakane, T., Kawabata, K., & Yamamoto, A. (2019). Utility of Three-Dimensional Skin From Human-Induced Pluripotent Stem Cells as a Tool to Evaluate Transdermal Drug Permeation. Journal of Pharmaceutical Sciences, 108(11), 3524–3527. https://doi.org/10.1016/j.xphs.2019.07.006
Neupane, R., Boddu, S. H. S., Renukuntla, J., Babu, R. J., & Tiwari, A. K. (2020). Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities. Pharmaceutics, 12(2), 152. https://doi.org/10.3390/pharmaceutics12020152
Nugroho, A. K. (2014). Compartmental Modeling Approach Of Losartan Transdermal Transport In Vitro. Indonesian Journal of Pharmacy, 25(1), 31. https://doi.org/10.14499/indonesianjpharm25iss1pp31
Pandey, G., & Rao, C. (2018). Andrographolide: Its pharmacology, natural bioavailability and current approaches to increase its content in andrographispaniculata. International Journal of Complementary & Alternative Medicine, 11(4). https://doi.org/10.15406/ijcam.2018.11.00425
Pawestri, S. A., Nugroho, A. K., & Lukitaningsih, E. (2021). In vitro Transdermal Transport of Domperidone by Compartmental Modeling Approach. Indonesian Journal of Pharmacy, 32(1), 10–16. https://doi.org/https://doi.org/10.22146/ijp.608
Preeti, Sambhakar, S., Malik, R., Bhatia, S., Al Harrasi, A., Rani, C., Saharan, R., Kumar, S., Geeta, & Sehrawat, R. (2023). Nanoemulsion: An Emerging Novel Technology for Improving the Bioavailability of Drugs. Scientifica, 2023, 1–25. https://doi.org/10.1155/2023/6640103
Pulsoni, I., Lubda, M., Aiello, M., Fedi, A., Marzagalli, M., Von Hagen, J., & Scaglione, S. (2022). Comparison Between Franz Diffusion Cell and a novel Micro-physiological System for In Vitro Penetration Assay Using Different Skin Models. SLAS Technology, 27(3), 161–171. https://doi.org/10.1016/j.slast.2021.12.006
Rodríguez-Luna, A., Talero, E., Ávila-Román, J., Romero, A. M. F., Rabasco, A. M., Motilva, V., & González-Rodríguez, M. L. (2021). Preparation and In Vivo Evaluation of Rosmarinic Acid-Loaded Transethosomes After Percutaneous Application on a Psoriasis Animal Model. AAPS PharmSciTech, 22(3), 103. https://doi.org/10.1208/s12249-021-01966-3
Singh, T., Arora, A., Sahu, K. K., Patel, P., Kaur, S., Thakur, S., Gupta, G. D., Singh, D., & Kurmi, B. D. (2024). A complete sojourn of recent advancements and applications in transdermal drug delivery systems. Journal of Drug Delivery Science and Technology, 102, 106328. https://doi.org/10.1016/j.jddst.2024.106328
Sohn, J. S., & Choi, J.-S. (2024). Development of a tadalafil transdermal formulation and evaluation of its ability to in vitro transdermal permeate using Strat-M® membrane. European Journal of Pharmaceutical Sciences, 192, 106615. https://doi.org/10.1016/j.ejps.2023.106615
Uchida, T., Kadhum, W. R., Kanai, S., Todo, H., Oshizaka, T., & Sugibayashi, K. (2015). Prediction of skin permeation by chemical compounds using the artificial membrane, Strat-MTM. European Journal of Pharmaceutical Sciences, 67, 113–118. https://doi.org/10.1016/j.ejps.2014.11.002
Waghule, T., Singhvi, G., Dubey, S. K., Pandey, M. M., Gupta, G., Singh, M., & Dua, K. (2019). Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotherapy, 109, 1249–1258. https://doi.org/10.1016/j.biopha.2018.10.078
Zou, L., Ding, W., Huang, Q., Yang, X., Li, J., Huang, T., Li, Z., Lin, S., & Feng, J. (2022). Andrographolide/Phospholipid/Cyclodextrin Complex-Loaded Nanoemulsion: Preparation, Optimization, in Vitro and in Vivo Evaluation. Biological and Pharmaceutical Bulletin, 45(8), 1106–1115. https://doi.org/10.1248/bpb.b22-00154
Amarah, A. A., Petlin, D. G., Grice, J. E., Hadgraft, J., Roberts, M. S., & Anissimov, Y. G. (2018). Compartmental modeling of skin transport. European Journal of Pharmaceutics and Biopharmaceutics, 130, 336–344. https://doi.org/10.1016/j.ejpb.2018.07.015
Anissimov, Y. G., Jepps, O. G., Dancik, Y., & Roberts, M. S. (2013). Mathematical and pharmacokinetic modelling of epidermal and dermal transport processes. Advanced Drug Delivery Reviews, 65(2), 169–190. https://doi.org/10.1016/j.addr.2012.04.009
Dai, Y., Chen, S.-R., Chai, L., Zhao, J., Wang, Y., & Wang, Y. (2019). Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Critical Reviews in Food Science and Nutrition, 59(sup1), S17–S29. https://doi.org/10.1080/10408398.2018.1501657
Green, M. H., & Green, J. B. (2022). The Use of Datasets for Theoretical Subjects to Validate Vitamin A–Related Methods and Experimental Designs. The Journal of Nutrition, 152(3), 707–713. https://doi.org/10.1093/jn/nxab441
Haq, A., Dorrani, M., Goodyear, B., Joshi, V., & Michniak-Kohn, B. (2018). Membrane properties for permeability testing: Skin versus synthetic membranes. International Journal of Pharmaceutics, 539(1–2), 58–64. https://doi.org/10.1016/j.ijpharm.2018.01.029
Kaur, L., Singh, K., Paul, S., Singh, S., Singh, S., & Jain, S. K. (2018). A Mechanistic Study to Determine the Structural Similarities Between Artificial Membrane Strat-MTM and Biological Membranes and Its Application to Carry Out Skin Permeation Study of Amphotericin B Nanoformulations. AAPS PharmSciTech, 19(4), 1606–1624. https://doi.org/10.1208/s12249-018-0959-6
Kaushik, S., Dar, L., Kaushik, S., & Yadav, J. P. (2021). Identification and characterization of new potent inhibitors of dengue virus NS5 proteinase from Andrographis paniculata supercritical extracts on in animal cell culture and in silico approaches. Journal of Ethnopharmacology, 267, 113541. https://doi.org/10.1016/j.jep.2020.113541
Kunita, R., Nishijima, T., Todo, H., Sugibayashi, K., & Sakaguchi, H. (2022). A Mathematical Approach Using Strat-M® to Predict the Percutaneous Absorption of Chemicals under Finite Dose Conditions. Pharmaceutics, 14(7), 1370. https://doi.org/10.3390/pharmaceutics14071370
Martihandini, N., Surini, S., & Bahtiar, A. (2021). Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study. Pharmaceutical Sciences, 1. https://doi.org/10.34172/PS.2021.76
Naito, C., Yamaguchi, T., Katsumi, H., Kimura, S., Kamei, S., Morishita, M., Sakane, T., Kawabata, K., & Yamamoto, A. (2019). Utility of Three-Dimensional Skin From Human-Induced Pluripotent Stem Cells as a Tool to Evaluate Transdermal Drug Permeation. Journal of Pharmaceutical Sciences, 108(11), 3524–3527. https://doi.org/10.1016/j.xphs.2019.07.006
Neupane, R., Boddu, S. H. S., Renukuntla, J., Babu, R. J., & Tiwari, A. K. (2020). Alternatives to Biological Skin in Permeation Studies: Current Trends and Possibilities. Pharmaceutics, 12(2), 152. https://doi.org/10.3390/pharmaceutics12020152
Nugroho, A. K. (2014). Compartmental Modeling Approach Of Losartan Transdermal Transport In Vitro. Indonesian Journal of Pharmacy, 25(1), 31. https://doi.org/10.14499/indonesianjpharm25iss1pp31
Pandey, G., & Rao, C. (2018). Andrographolide: Its pharmacology, natural bioavailability and current approaches to increase its content in andrographispaniculata. International Journal of Complementary & Alternative Medicine, 11(4). https://doi.org/10.15406/ijcam.2018.11.00425
Pawestri, S. A., Nugroho, A. K., & Lukitaningsih, E. (2021). In vitro Transdermal Transport of Domperidone by Compartmental Modeling Approach. Indonesian Journal of Pharmacy, 32(1), 10–16. https://doi.org/https://doi.org/10.22146/ijp.608
Preeti, Sambhakar, S., Malik, R., Bhatia, S., Al Harrasi, A., Rani, C., Saharan, R., Kumar, S., Geeta, & Sehrawat, R. (2023). Nanoemulsion: An Emerging Novel Technology for Improving the Bioavailability of Drugs. Scientifica, 2023, 1–25. https://doi.org/10.1155/2023/6640103
Pulsoni, I., Lubda, M., Aiello, M., Fedi, A., Marzagalli, M., Von Hagen, J., & Scaglione, S. (2022). Comparison Between Franz Diffusion Cell and a novel Micro-physiological System for In Vitro Penetration Assay Using Different Skin Models. SLAS Technology, 27(3), 161–171. https://doi.org/10.1016/j.slast.2021.12.006
Rodríguez-Luna, A., Talero, E., Ávila-Román, J., Romero, A. M. F., Rabasco, A. M., Motilva, V., & González-Rodríguez, M. L. (2021). Preparation and In Vivo Evaluation of Rosmarinic Acid-Loaded Transethosomes After Percutaneous Application on a Psoriasis Animal Model. AAPS PharmSciTech, 22(3), 103. https://doi.org/10.1208/s12249-021-01966-3
Singh, T., Arora, A., Sahu, K. K., Patel, P., Kaur, S., Thakur, S., Gupta, G. D., Singh, D., & Kurmi, B. D. (2024). A complete sojourn of recent advancements and applications in transdermal drug delivery systems. Journal of Drug Delivery Science and Technology, 102, 106328. https://doi.org/10.1016/j.jddst.2024.106328
Sohn, J. S., & Choi, J.-S. (2024). Development of a tadalafil transdermal formulation and evaluation of its ability to in vitro transdermal permeate using Strat-M® membrane. European Journal of Pharmaceutical Sciences, 192, 106615. https://doi.org/10.1016/j.ejps.2023.106615
Uchida, T., Kadhum, W. R., Kanai, S., Todo, H., Oshizaka, T., & Sugibayashi, K. (2015). Prediction of skin permeation by chemical compounds using the artificial membrane, Strat-MTM. European Journal of Pharmaceutical Sciences, 67, 113–118. https://doi.org/10.1016/j.ejps.2014.11.002
Waghule, T., Singhvi, G., Dubey, S. K., Pandey, M. M., Gupta, G., Singh, M., & Dua, K. (2019). Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotherapy, 109, 1249–1258. https://doi.org/10.1016/j.biopha.2018.10.078
Zou, L., Ding, W., Huang, Q., Yang, X., Li, J., Huang, T., Li, Z., Lin, S., & Feng, J. (2022). Andrographolide/Phospholipid/Cyclodextrin Complex-Loaded Nanoemulsion: Preparation, Optimization, in Vitro and in Vivo Evaluation. Biological and Pharmaceutical Bulletin, 45(8), 1106–1115. https://doi.org/10.1248/bpb.b22-00154
Published
2026-07-17
How to Cite
Nugroho, A. K. ., Anindhita, M. A., Zai, K., & Hertiani, T. (2026). Compartmental Kinetic Modeling of In Vitro Transdermal Permeation Across Strat-M® Membranes: A Case of Andrographis paniculata Extract Nanoemulsion. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.29693
Issue
Section
Research Article
