Modeling and Optimization of Mitragyna speciosa Extraction using Box Behnken Design

Azka M. Rusydan(1), Endang Lukitaningsih(2*), Nanang Fakhrudin(3)

(1) Master Program, Faculty of Pharmacy, Universitas Gadjah Manda, Yogyakarta
(2) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University Gadjah Mada, Jl Sekip Utara, Yogyakarta
(3) Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author


The extraction of kratom (M. speciosa) leaf powder was optimized with preliminary extraction to be further optimized with the Box-Behnken experimental design. The individual and interactive effects of process variables (sample-to-solvent ratio, extraction time, solvent concentration) were assessed. The preliminary extraction results showed that ultrasound-assisted extraction (UAE) and methanol were chosen for further optimization. The experimental data were analyzed by Pareto analysis of variance (ANOVA) and second-order polynomial models were developed using multiple regression analysis. The model developed showed a good fit with the experimental data with a high coefficient of correlation (R2) and predictive ability (predicted R2). An optimization study was performed and the optimal extraction conditions were sample-to-solvent ratio value 1.5:10; extraction time of 10 minutes, and methanol concentration of 100%.


Kratom; Mitragyna speciosa; mitragynine; Ultrasound-assisted extraction

Full Text:



Ahmad, A., Alkharfy, K.M., Wani, T.A., and Raish, M., 2015. Application of Box–Behnken design for ultrasonic-assisted extraction of polysaccharides from Paeonia emodi. International Journal of Biological Macromolecules, 72: 990–997.

Andilala, 2019. 'BNN: Kratom dilarang total mulai 2022', Antara News. URL: (accessed 6/3/2020).

Assanangkornchai, S., Muekthong, A., Sam-angsri, N., and Pattanasattayawong, U., 2007. The Use of Mitragynine speciosa (“Krathom”), an Addictive Plant, in Thailand. Substance Use & Misuse, 42: 2145–2157.

Badan Pengawas Obat dan Makanan, 2016. Surat Edaran No. HK. Tahun2016 Tentang Pelarangan Penggunaan Mitragyna Speciosa (Kratom) Dalam Obat Tradisional Dan Suplemen Kesehatan.

Byrne, C., 2017. Misuse of Drugs (Designation) Order 2017. Office of the Attorney General.

Chemat, F. and Strube, J., 2015. Green Extraction of Natural Products- Theory and Practice. Wiley-VCH Verlag GmvH & Co., Weinheim, Germany.

Chua, L.S.L. and Schmelzer, G.H., 2001. Mitragyna speciosa (Korth.) Havil. Medicinal and Poisonous Plants 2, 380–382.

Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu, A., et al., 2015. 'Following “the Roots” of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries', , Research Article, BioMed Research International. URL: (accessed 1/2/2020).

Elsa, L., 2016. Pengembangan Metode Isolasi dan Identifikasi Mitragynine dalam Daun Kratom (Mitragyna speciosa). Jurnal Biosains Pascasarjana, 18: 191.

EMCDDA, 2012. 'Kratom (Mitragyna speciosa) drug profile', Kratom Drug Profile. URL: (accessed 12/2/2020).

Fu, H., Cid, F., Dworkin, N., Cocores, J., and Shore, G., 2015. Screening and Identification of Mitragynine and 7-Hydroxymitragynine in Human Urine by LC-MS/MS. Chromatography, 2: 253–264.

Great Britain, 2016. Psychoactive Substances Act 2016.

Handa, S.S., Khanuja, S.P.S., Longo, G., and Rakesh, D.D., 2008. Extraction Technologies for Medicinal and Aromatic Plants. International Centre for Science and High Technology, Trieste, Italy.

Kowalczuk, A.P., Łozak, A., and Zjawiony, J.K., 2013. Comprehensive methodology for identification of Kratom in police laboratories. Forensic Science International, 233: 238–243.

Mandal, S.C., Mandal, V., and Das, A.K., 2015. Essentials of Botanical Extraction: Principles and Applications. Elsevier/AP, Academic Press is an imprint of Elsevier, Amsterdam ; Boston.

Menteri Pertanian Republik Indonesia, 2020. Keputusan Menteri Pertanian Republik Indonesia Nomor 104/Kpts/Hk.140/M/2/2020 Tentang Komoditas Binaan Kementerian Pertanian.

Prozialeck, W.C., Jivan, J.K., and Andurkar, S.V., 2012. Pharmacology of Kratom: An Emerging Botanical Agent With Stimulant, Analgesic and Opioid-Like Effects. J Am Osteopath Assoc., 112: 792–799.

Raffa, R.B., n.d. Kratom and Other Mitragynines 356.

Raffa, R.B., Beckett, J.R., Brahmbhatt, V.N., Ebinger, T.M., Fabian, C.A., Nixon, J.R., et al., 2013. Orally Active Opioid Compounds from a Non-Poppy Source. Journal of Medicinal Chemistry, 56: 4840–4848.

Ratsch, C., 2005. The Encyclopedia of Psychoactive Plants. Park Street Press, Rochester.

Razafimandimbison, S.G. and Bremer, B., 2001. Tribal Delimitation of Naucleeae (Cinchonoideae, Rubiaceae): Inference from Molecular and Morphological Data. Systematics and Geography of Plants, 71: 515–538.

Rokib, M., 2019. 'Kepala BBPOM Beri Penjelasan Terkait Larangan Jual Kratom Dalam Bentuk Olahan - Tribun Pontianak', . URL: (accessed 17/6/2020).

Singh, D., Narayanan, S., Müller, C.P., Swogger, M.T., Chear, N.J.Y., Dzulkapli, E.B., et al., 2019. Motives for using Kratom (Mitragyna speciosa Korth.) among regular users in Malaysia. Journal of Ethnopharmacology, 233: 34–40.

Suwanlert, S., 1975. A Study of Kratom Eaters in Thailand. Buletin on Narcotics, 27: 21–27.

Tanguay, P., 2011. 'Kratom in Thailand', , SSRN Scholarly Paper, Social Science Research Network, Rochester, NY.


Article Metrics

Abstract views : 870 | views : 1702


  • There are currently no refbacks.

Copyright (c) 2021 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada