Development and validation of high-performance liquid chromatography method for the simultaneous quantification of rivastigmine hydrogen tartrate and asiaticoside co-loaded in niosomes: A Box–Behnken design approach
Abstract
Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, is considered as the first-line therapy for mild to moderate Alzheimer's disease. Asiaticoside (AS), a pentacyclic triterpenoid saponin, is well known as cognitive enhancer due to its antioxidant effect. Based on the hypothesis of their synergistic therapeutic potential, RHT and AS were co-encapsulated in niosomal formulation. A simple, precise, and accurate high-performance liquid chromatography method was developed for simultaneous quantitative analysis. The chromatographic parameters were optimized by Box-Behnken experimental design. The separation was performed on a reversed-phase Phenomenex C18 (150 mm × 4.6 mm, 5 μm) column at 30 °C under the UV detection of 210 nm. The optimized mobile phase consisted of a mixture of 20 mM potassium dihydrogen phosphate buffer (pH 2.6) and acetonitrile (72:28 % v/v) under the isocratic mode at the flow rate of 0.9 mL/min. The developed method was fully validated under the ICH guidelines and could be successfully applied for simultaneous quantitative analysis of RHT and AS in niosomal formulation.
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Niosome formulations incorporating asiaticoside showed improved stability, sustained release, and deep epidermal delivery.
“Formulations incorporating asiaticoside showed improved stability, sustained release, and deep epidermal delivery (Hnin et al. 2024; Wichayapreechar et al. 2020).”
From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Hnin et al. 2024
Niosomal and liposomal systems facilitated sustained dermal retention of asiaticoside, often enhanced by surfactant modifications or hyaluronic acid coating.
“Niosomal and liposomal systems further facilitated sustained dermal retention of asiaticoside, often enhanced by surfactant modifications or hyaluronic acid coating (Hnin et al. 2024; Liu et al. 2020).”
From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Hnin et al. 2024
Cites
1 retracted
RETRACTED: Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice
Lin, X., Huang, R., Zhang, S., Wei, L., Zhuo, L., Wu, X., Tang, A., & Huang, Q. (2013) · Fitoterapia · doi:10.1016/j.fitote.2013.03.023 · Cited by 37 · see citing works
RetractedOutcomes of Alzheimer's disease therapy with acetylcholinesterase inhibitors and memantine
Zemek, F., Drtinová, L., Nepovimová, E., Šepsová, V., Korábečný, J., Klimeš, J., & Kuča, K. (2014) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2014.914168 · Cited by 307 · see citing works
Veerendra Kumar, M., & Gupta, Y. (2003) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2003.03842.x · Cited by 249 · see citing works
Yang, Z.-Z., Zhang, Y.-Q., Wang, Z.-Z., Wu, K., Lou, J.-N., & Qi, X.-R. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.05.009 · Cited by 248 · see citing works
Shah, B. M., Khunt, D., Bhatt, H., Misra, M., & Padh, H. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.07.002 · Cited by 237 · see citing works
Cholinesterases and the Pathology of Alzheimer Disease
Geula, C., & Mesulam, M. ‐. (1995) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199501002-00005 · Cited by 193 · see citing works
Simon, A., Amaro, M. I., Healy, A. M., Cabral, L. M., & de Sousa, V. P. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.08.052 · Cited by 171 · see citing works
A study of rivastigmine liposomes for delivery into the brain through intranasal route
Arumugam, K., Subramanian, G., Mallayasamy, S., Averineni, R. K., Reddy, M. S., & Udupa, N. (2008) · Acta Pharmaceutica · doi:10.2478/v10007-008-0014-3 · Cited by 162 · see citing works
Guidelines for the Management of Cognitive and Behavioral Problems in Dementia
Sadowsky, C., & Galvin, J. E. (2012) · The Journal of the American Board of Family Medicine · doi:10.3122/jabfm.2012.03.100183 · Cited by 141 · see citing works
DANTOINE, T. F., Auriacombe, S., Sarazin, M., Becker, H., Pere, J.-J., & Bourdeix, I. (2005) · International Journal of Clinical Practice · doi:10.1111/j.1368-5031.2005.00769.x · Cited by 106 · see citing works
Wavikar, P., Pai, R. V., & Vavia, P. R. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.08.024 · Cited by 103 · see citing works
Gottwald, M. D., & Rozanski, R. I. (1999) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.8.10.1673 · Cited by 91 · see citing works
Kulkarni, P., Rawtani, D., & Barot, T. D. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.02.015 · Cited by 86 · see citing works
Narisepalli, S., Salunkhe, S. A., Chitkara, D., & Mittal, A. (2022) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2022.122508 · Cited by 79 · see citing works
Arora, R., Kumar, R., Agarwal, A., Reeta, K. H., & Gupta, Y. K. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.05.156 · Cited by 73 · see citing works
Elkady, E. F., Fouad, M. A., & Mozayad, A. N. (2022) · BMC Chemistry · doi:10.1186/s13065-022-00908-9 · Cited by 69 · see citing works
Khalil, R. M., Abdelbary, G. A., Basha, M., Awad, G. E. A., & El-Hashemy, H. A. (2016) · Journal of Liposome Research · doi:10.1080/08982104.2016.1191022 · Cited by 68 · see citing works
Alhajabdalla, M., Mahmoud, H., Nasser, M. S., Hussein, I. A., Ahmed, R. M., & Karami, H. (2021) · ACS Omega · doi:10.1021/acsomega.0c04272 · Cited by 59 · see citing works
Salwa, & Kumar, L. (2023) · Microchemical Journal · doi:10.1016/j.microc.2023.108944 · Cited by 47 · see citing works
Francis, P. T., Parsons, C. G., & Jones, R. W. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.124 · Cited by 45 · see citing works
Synergistic Effects of Galantamine and Memantine in Attenuating Scopolamine-Induced Amnesia in Mice
Busquet, P., Capurro, V., Cavalli, A., Piomelli, D., Reggiani, A. M., & Bertorelli, R. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.12166sc · Cited by 44 · see citing works
Reverse-phase high performance liquid chromatography of asiaticoside in Centella asiatica
Verma, R. K., Bhartariya, K. G., Gupta, M. M., & Kumar, S. (1999) · Phytochemical Analysis · doi:10.1002/(sici)1099-1565(199907/08)10:4 · Cited by 43 · see citing works
Hnin, H. M., Stefánsson, E., Loftsson, Þ., Asasutjarit, R., Charnvanich, D., & Jansook, P. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061147 · Cited by 40 · see citing works
Self-citationA stability indicating LC method for Rivastigmine hydrogen tartrate
Rao, B. M., Srinivasu, M. K., Kumar, K. P., Bhradwaj, N., Ravi, R., Mohakhud, P. K., Reddy, G. O., & Kumar, P. (2005) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2004.09.041 · Cited by 40 · see citing works
Jisha, S. P., Gouri, P. R., Anith, K. N., & Sabu, K. K. (2018) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2018.01.021 · Cited by 34 · see citing works
Burilova, E. A., Pashirova, T. N., Zueva, I. V., Гибадуллина, Э. М., Lushchekina, S. V., Sapunova, А. S., Kayumova, R. M., Rogov, A. M., Evtugyn, V. G., Sudakov, I. A., et al. (2020) · Nanoscale · doi:10.1039/d0nr04037a · Cited by 27 · see citing works
Panichpakdee, J., & Supaphol, P. (2011) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2011.02.023 · Cited by 18 · see citing works
Amaro, M. I., Simon, A., Cabral, L. M., de Sousa, V. P., & Healy, A. M. (2015) · Solid State Sciences · doi:10.1016/j.solidstatesciences.2015.09.004 · Cited by 17 · see citing works
Mullangi, R., Ranjithkumar, A., Arumugam, K., Mallayasamy, S., Ganesan, S., Jamadar, L. D., Udupa, N., & Chamallamudi, M. R. (2011) · Journal of Young Pharmacists · doi:10.4103/0975-1483.90244 · Cited by 17 · see citing works
Sokol, M. B., Gulyaev, I., Mollaeva, M. R., Кузнецов, С. Л., Zenin, V. A., Klimenko, M. A., Yabbarov, N. G., Chirkina, M., & Nikolskaya, E. D. (2022) · Journal of Separation Science · doi:10.1002/jssc.202200731 · Cited by 14 · see citing works
Huda, N. H., Gauri, B., Benson, H. A., & Chen, Y. (2018) · Journal of Analytical Methods in Chemistry · doi:10.1155/2018/1841937 · Cited by 9 · see citing works
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Handayani, R., Febriyanti, R. M., Muhaimin, M., & Chearunisaa, A. Y. (2025) · Pharmacia · doi:10.3897/pharmacia.72.e167217 · Cited by 5 · see citing works
Advances in Pharmaceutical Analytical Technology
Oliva, A. (2025) · Molecules · doi:10.3390/molecules30102155 · Cited by 3 · see citing works
Monton, C., & Suksaeree, J. (2024) · Scientifica · doi:10.1155/sci5/6177990 · Cited by 2 · see citing works
Saleh, A. Y., Saputra, D. A. Y., Valentina, R., & Susanto, T. D. (2025) · F1000Research · doi:10.12688/f1000research.160416.3 · Cited by 1 · see citing works
Saleh, A. Y., Saputra, D. A. Y., Valentina, R., & Susanto, T. D. (2025) · F1000Research · doi:10.12688/f1000research.160416.1 · Cited by 1 · see citing works
Hnin, H. M., Tun, T., Chongcharoen, W., Nalinratana, N., Rodsiri, R., Loftsson, Þ., Parekh, H. S., & Jansook, P. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.152709
Self-citationAmlashi, N. E., Yamini, Y., Dadgarnejad, S., & Hadjmohammadi, M. R. (2026) · Journal of Analytical Chemistry · doi:10.1134/s1061934825602762
- Authors
- Hnin, H. M., Tun, T., & Jansook, P.
- Affiliations
- Chulalongkorn University (TH)
- Corresponding author
- Jansook, Phatsawee
- Venue
- Journal of Chromatography B
- Publisher
- Elsevier BV
- Published
- 2024-07
- Volume
- 1241
- Pages
- 124170
- ISSN
- 1570-0232 (ISSN-L)
- OpenAlex
- W4398238701
- Cited by
- 7
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Chromatography B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Thailand Science Research and Innovation
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Physical Sciences › Chemistry › Spectroscopy › Analytical Chemistry and Chromatography
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- asiaticoside, niosomes, simultaneous determination, HPLC method development, Box-Behnken design, drug co-loading, Alzheimer's disease, cholinesterase inhibitors, pentacyclic triterpenoid saponins, drug delivery formulation, method validation
- MeSH terms
- Rivastigmine, Chromatography, High Pressure Liquid, Liposomes, Triterpenes, Reproducibility of Results, Linear Models, Limit of Detection
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