• NURUL FAJERIYATI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia, Faculty of Pharmacy, University of Muhammadiyah Banjarmasin, Banjarmasin, Indonesia
  • MUCHTARIDI MUCHTARIDI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia
  • IYAN SOPYAN Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjdjaran University, Sumedang, Indonesia



Alpha-mangostin, Solubility, Drug delivery system


Solubility is an important parameter to achieve for the bioavailability of a drug to reach the therapeutic windows. Garcinia mangostana Linn is a plant with great potency for the development of natural medicine. Alpha-mangostin is one of the secondary metabolites of G. mangostana and has been reported to have several pharmacological activities. The Biopharmaceutics Classification System (BCS) is a system that classifies drugs based on their solubility and permeability. Due to its low solubility but high permeation, alpha-mangostin is categorized into class II of the Biopharmaceutics Classification System. Therefore, the determination of dosage forms and modification of solubility enhancers is limited due to its physical properties, as mentioned above. This disadvantage requires new methods to improve its solubility to administer alpha-mangostin, especially for oral administration. Here, we discuss the development of the methods to increase alpha-mangostin solubility to be applied to formulate a dosage form to reach a useful plasma level for medication.


Download data is not yet available.


Rohn J. Pharmacokinetics and preformulation; 2017. p. 17–37.

Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. Int J Pharm Sci Rev Res 2010;5:41–51.

Schimid DW. Ueber Mangostin; 1849. p. 83–8.

Ahmad M, Yamin BM, Lazim AM. A study on dispersion and characterization of α-mangostin loaded pH sensitive microgel systems. Chem Central J 2013;85:2–7.

Aisha AFA, Malik A, Abdulmajid S, Ismail Z, Alrokayan SA, Abu-salah KM. Development of polymeric nanoparticles of garcinia mangostana xanthones in eudragit RL100/RS100 for anti-colon cancer drug delivery. J Nanomaterials 2015;7:1-12.

Fei X, Jo M, Lee B, Han SB, Lee K, Jung JK, et al. Synthesis of xanthone derivatives based on α-mangostin and their biological evaluation for anti-cancer agents. Bioorg Med Chem Lett 2014;24:2062–5.

Muchtaridi M, Wijaya CA. Anticancer potential of alpha-mangostin. Asian J Pharm Clin Res 2017;10:440-5.

Sampath PD, Vijayaraghavan K. Cardioprotective effect of α-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-inducedmyocardial infarction in rats. J Biochem Mol Toxicol 2007;21:336–9.

Chen LG, Yang LL, Wang CC. Anti-inflammatory activity of mangostins from garcinia mangostana. Food Chem Toxicol 2008;46:688–93.

Pothitirat W, Chomnawang MT, Supabphol R, Gritsanapan W. Comparison of bioactive compounds content, free radical scavenging and anti-acne inducing bacteria activities of extracts from the mangosteen fruit rind at two stages of maturity. Fitoterapia 2009;80:442–7.

Sudta P, Jiarawapi P, Suksamrarn A, Hongmanee P, Suksamrarn S. Potent activity against multidrug-resistant mycobacterium tuberculosis of α-mangostin analogs. Chem Pharm Bull 2013;61:194–203.

Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD. Antioxidant xanthones from the pericarp of garcinia mangostana (mangosteen). J Agric Food Chem 2006;54:2077–82.

Koh JJ, Qiu S, Zou H, Lakshminarayanan R, Li J, Zhou X, et al. Rapid bactericidal action of alpha-mangostin against MRSA as an outcome of membrane targeting. Biochim Biophys Acta 2013;1828:834–44.

Wathoni N, Yuniarsih N, Cahyanto A, Muhctaridi M. Α-mangostin hydrogel film based chitosan-alginate for recurrent aphthous stomatitis. Appl Sci 2019;9:1-14.

Kaomongkolgit R, Jamdee K, Chaisomboon N. Antifungal activity of alpha-mangostin against Candida albicans. J Oral Sci 2009;51:401–6.

Zhao Y, Tang G, Tang Q, Zhang J, Hou Y, Cai E, et al. A method of effectively improved α-mangostin bioavailability. Eur J Drug Metab Pharmacokinet 2016;41:605–13.

Aisha AFA, Ismail Z, Abu-Salah KM, Majid AMSA. Solid dispersions of α-mangostin improve its aqueous solubility through self-assembly of nanomicelles. J Pharm Sci 2011;101:815–25.

Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm 2012;1–10. DOI: 10.5402/2012/195727.

Kerns E, Di L, Carter G. In vitro solubility assays in drug discovery. Curr Drug Metab 2008;9:879–85.

Kasimedua S, Thoppani SR, Pommalab N, Orugonda G, Yelamanda J. A review on solubility enhancement techniques. J Compr Pharm 2015;2:36–41.

Mantri RV, Sanghvi R, Zhu HJ. Solubility of pharmaceutical solids. Developing solid oral dosage forms: pharmaceutical theory and practice: 2nd Edition. Elsevier Inc; 2017. p. 3-22.

Patil SS, Ram Mohan Gupta V, Srikanth Gupta K, Doddayya H. Effect of ph, selected cyclodextrins and complexation methods on the solubility of lornoxicam. Int J Pharm Pharm Sci 2014;6:324–7.

Kansara H, Panola R, Mishra A. Techniques used to enhance the bioavailability of bcs class II drugs: a review. Int J Drug Dev Res 2015;7:82–93.

Chaudhary A, Nagaich U, Gulati N, Sharma V, Khosa R, Partapur M. Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications: a recent review. J Adv Pharm Educ Res 2012;2:32–67.

Sanjaymitra P, Ganesh G. Dissolution and solubility enhancement strategies: current and novel prospectives. J Crit Rev 2018;5:1–10.

Dahan A, Miller JM, Amidon GL. Prediction of solubility and permeability class membership: provisional BCS classification of the world’s top oral drugs. AAPS J 2009;11:740–6.

Yasir M, Asif M, Kumar A, Aggarval A. Biopharmaceutical classification system: an account. Int J PharmTech Res 2010;2:1681–90.

Vermeersdch H. Solubility and permeation studies using soluplus® and hpmc with a bcs class ii amorphous drug. J Pharm Res Int 2016;18:1-40.

Li L, Brunner I, Han AR, Hamburger M, Kinghorn AD, Frye R, et al. Pharmacokinetics of α-mangostin in rats after intravenous and oral application. Mol Nutr Food Res 2011;55 Suppl 1:67–74.

Alpha mangostin. Available from: [Last accessed on 10 Jul 2020]

Ramaiya A, Li G, M Petiwala S, J Johnson J. Single-dose oral pharmacokinetic profile of α-mangostin in mice. Curr Drug Targets 2012;13:1698–704.

Pan-In P, Tachapruetinun A, Chaichanawongsaroj N, Banlunara W, Suksamrarn S, Wanichwecharungruang S. Combating helicobacter pylori infections with mucoadhesive nanoparticles loaded with garcinia mangostana extract. Nanomedicine 2014;9:457–68.

Pan-In P, Wanichwecharungruang S, Hanes J, Kim AJ. Cellular trafficking and anticancer activity of garcinia mangostana extract-encapsulated polymeric nanoparticles. Int J Nanomed 2014;9:3677–86.

Chin GS, Todo H, Kadhum WR, Hamid MA, Sugibayashi K. In vitro permeation and skin retention of α mangostin proniosome. pdf. Chem Pharm Bull 2016;64:1666-73.

Yang S, Gao X, He Y, Hu Y, Xu B, Cheng Z, et al. Applying an innovative biodegradable self-assembly nanomicelles to deliver αmangostin for improving anti-melanoma activity. Cell Death Disease 2019;10:146.

Samprasit W, Rojanarata T, Akkaramongkolporn P, Ngawhirunpat T, Kaomongkolgit R, Opanasopit P. Fabrication and in vitro in vivo performance of mucoadhesive electrospun nanofiber mats containing α mangostin. AAPS PharmSciTech 2015;16:1-13.

Xu WK, Jiang H, Yang K, Wang YQ, Zhang Q, Zuo J. Development and in vivo evaluation of self-microemulsion as the delivery system for α-mangostin. Kaohsiung J Med Sci 2017;33:116–23.

Limwikrant W, Aung T, Chooluck K, Puttipipatkhachorn S, Yamamoto K. Size reduction efficiency of alpha-mangostin suspension using high-pressure homogenization. Chem Pharm Bull 2019;67:389–92.

Elsaid Ali AA, Taher M, Mohamed F. Microencapsulation of alpha-mangostin into PLGA microspheres and optimization using response surface methodology intended for pulmonary delivery. J Microencapsul 2013;30:728–40.

Iqbal A, Muhammad Shuib NA, Darnis DS, Miskam M, Abdul Rahman NR, Adam F. Synthesis and characterisation of rice husk ash silica drug carrier for α-mangostin. J Phys Sci 2018;29:95–107.

Phunpee S, Suktham K, Surassmo S, Jarussophon S, Rungnim C, Soottitantawat A, et al. Controllable encapsulation of α-mangostin with quaternized β-cyclodextrin grafted chitosan using high shear mixing. Int J Pharm 2018;538:21–9.

Hotarat W, Phunpee S, Rungnim C, Wolschann P, Kungwan N, Ruktanonchai U, et al. Encapsulation of alpha-mangostin and hydrophilic beta-cyclodextrins revealed by all-atom molecular dynamics simulations. J Mol Liq 2019;288:110965.

Liza P, Fudholi A, Martien R, Pramono S. Self-nano emulsifying drug delivery system (snedds) for topical delivery of mangosteen peels (garcinia mangostana l.,): formulation design and in vitro studies. J Young Pharm 2017;9:107–14.

Kalepu S, Nekkanti V. Improved delivery of poorly soluble compounds using nanoparticle technology: a review. Drug Delivery Transl Res 2016;6:319–32.

Irving B. Nanoparticle drug delivery systems. Innovations in Pharmaceutical Technology; 2007.

Mishra R, Mir SR, Amin S. Polymeric nanoparticles for improved bioavailability of cilnidipine. Int J Pharm Pharm Sci 2017;9:129.

Bozic M, Elschner T, Tkaucic D, Bracic M, Hribernik S, Stana Kleinschek K, et al. Effect of different surface-active polysaccharide derivatives on the formation of ethyl cellulose particles by the emulsion-solvent evaporation method. Cellulose 2018;25:6901–22.

Pan-in P, Wongsomboon A, Kokpol C. Depositing a-mangostin nanoparticles to sebaceous gland area for acne treatment. J Pharmacol Sci 2015;129:226–32.

Wathoni Nasrul, Rusdin Agus, Febriani Erma, Purnama Destiana, Daulay Wahnidar, Azhary Sundoro Y, et al. Formulation and characterization of α-mangostin in chitosan nanoparticles coated by sodium alginate, sodium silicate, and polyethylene glycol. J Pharm Bioallied Sci 2019;11:619-27.

Herdiana Yedi, Handaresta Devi Fitria, Joni I Made, Wathoni Nasrul. Synthesis of nano-α mangostin based on chitosan and eudragit S 100. J Adv Pharm Technol Res 2020;11:95-100.

Minnick DL, Flores RA, Destefano MR, Scurto AM. Cellulose solubility in ionic liquid mixtures: temperature, cosolvent, and antisolvent e ff ects. J Phys Chem B 2016;120:7906–19.

Chaudhari SP, Dugar RP. Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs. J Drug Delivery Sci Technol 2017;41:68–77.

Recharla N, Riaz M, Ko S, Park S. Novel technologies to enhance solubility of food-derived bioactive compounds: a review. J Funct Foods 2017;39:63–73.

Crabbe Mann M, Tsaoulidis D, Parhizkar M, Edirisinghe M. Ethyl cellulose, cellulose acetate and carboxymethyl cellulose microstructures prepared using electrohydrodynamics and green solvents. Cellulose 2018;25:1687–703.

Zoubari G, Ali R, Dashevskiy A. Water-soluble and-insoluble polymers as binders for pellet preparation by extrusion/spheronization. J Drug Delivery Sci Technol 2019;49:1–5.

Mazumder S, Dewangan AK, Pavurala N. Enhanced dissolution of poorly soluble antiviral drugs from nanoparticles of cellulose acetate based solid dispersion matrices. Asian J Pharm Sci 2017;12:532–41.

Anand S, Gupta R, Sk P. Self-microemulsifying drug delivery system. Asian J Pharm Clin Res 2016;9:1.

Tobergte DR, Curtis S. Self microemulsifying drug delivery system: a lipid based drug delivery system. J Chem Inf Model 2013;53:1689–99.

Nasr A, Gardouh A, Ghorab M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics 2016;8:20.

Chavda VP, Shah D. Self-emulsifying delivery systems: one step ahead in improving solubility of poorly soluble drugs. Nanostructures for Cancer Therapy. Elsevier Inc.; 2017. p. 653-718.

Singh H, Nathani S, Singh N, Roy P, Paul S, Sohal HS, et al. Development and characterization of solid-SNEDDS formulation of DHA using hydrophilic carrier with improved shelf life, oxidative stability and therapeutic activity. J Drug Delivery Sci Technol 2019;54:101326.

Chaudhary S, Aqil M, Sultana Y, Kalam MA. Self-nanoemulsifying drug delivery system of nabumetone improved its oral bioavailability and anti-inflammatory effects in rat model. J Drug Delivery Sci Technol 2019;51:736–45.

Talele SG, Derle DV. Solubility and thermodynamic modeling of quetiapine fumarate in self nanoemulsifying drug delivery system (SNEDDS). Int J Appl Pharm 2018;10:127–32.

Akhtar N, Khan RA, Mohammad SAA, Yusuf M, Singh V, Mohammad HAA, et al. Self-generating nano-emulsifying technology for alternatively-routed, bioavailability enhanced delivery, especially for anti-cancers, anti-diabetics, and miscellaneous drugs. J Drug Delivery Sci Technol 2020;1:101808.

Sanka K, Suda D, Bakshi V. Optimization of solid-self nanoemulsifying drug delivery system for solubility and release profile of clonazepam using simplex lattice design. J Drug Delivery Sci Technol 2016;33:114–24.

Zaini E, Putri VZ, Octavia MD, Ismed F. Peningkatan laju disolusi dispersi padat amorf genistein dengan PVP K-30. J Sains Farm Klin 2017;4:67.

Gurunath S, Pradeep Kumar S, Basavaraj NK, Patil PA. Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs. J Pharm Res 2013;6:476–80.

Ogawa N, Hiramatsu T, Suzuki R, Okamoto R, Shibagaki K, Fujita K, et al. Improvement in the water solubility of drugs with a solid dispersion system by spray drying and hot-melt extrusion with using the amphiphilic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and D-mannitol. Eur J Pharm Sci 2018;111:205–14.

Kumar, B. Solid dispersion-a review. PharmaTutor 2017;5:24–9.

Singh J, Walia M, Harikumar SL. Solubility enhancement by solid dispersion method: a review. J Drug Delivery Ther 2013;3:148–55.

Kaur J, Aggarwal G, Singh G, Rana AC. Improvement of drug solubilty using solid dispersion. J Pharmacol Sci 2012;4:47-53.

Tran P, Pyo YC, Kim DH, Lee SE, Kim JK, Park JS. Overview of the manufacturing methods of solid dispersion technology for improving the solubility of poorly water-soluble drugs and application to anticancer drugs. Pharmaceutics 2019;11:1–26.

Jelic D, Liavitskaya T, Vyazovkin S. Thermal stability of indomethacin increases with the amount of polyvinylpyrrolidone in solid dispersion. Thermochim Acta 2019;676:172–6.

Bibby DC, Davies NM, Tucker IG. Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems. Int J Pharm 2000;197:1–11.

Doan VTH, Lee JH, Takahashi R, Nguyen PTM, Nguyen VAT, Pham HTT, et al. Cyclodextrin based nanoparticles encapsulating α mangostin and their drug release behavior. Polymer J 2019;52:1-10.

Dermawan D, Wathoni N, Muchtaridi M. Host guest interactions of α mangostin with (α,β,γ) cyclodextrins. pdf. J Young Pharm 2019;11:31–5.

Hotarat W, Nutho B, Peter Wolschann, Rungrotmongkol T, Hannongbua S. Delivery of alpha-mangostin using cyclodextrins through a biological membrane. Molecular 2020;25:2532.

Shihong Q, Granet R, Mbakidi JP, Bregier F, Pouget C, Micallef, et al. Delivery of tanshinone IIA and α mangostin from gold PEI cyclodextrin nanoparticle platform design for prostat cancer. Bioorganic Med Chem Lett 2016;26:2503-6.

Wathoni N, Sari DP, Suharyani I, Motoyama K, Mohammed AFA, Cahyanto A, et al. Enhancement of α-mangostin wound healing ability by complexation with 2-hydroxypropyl-β-cyclodextrin in hydrogel formulation. Pharmaceuticals 2020;13:1–16.

Adhikar L, Semalty A, Semalty M. Binary complexes of glimepiride with β-cyclodextrin for improved solubility and drug delivery. Indian Drugs 2019;56:54-60.

Pranjali W Chandurkara, Tushar A Shindea, Anup M Akarteb PPR. Effect of trimethoprim inclusion complexation with cyclodextrins on its antimicrobial activity. Chem Methodol 2018;3:211–25.



How to Cite

FAJERIYATI, N., MUCHTARIDI, M., & SOPYAN, I. (2021). METHODS FOR IMPROVING ALPHA-MANGOSTIN SOLUBILITY: A REVIEW. International Journal of Applied Pharmaceutics, 13(4), 47–54.



Review Article(s)

Most read articles by the same author(s)

1 2 3 > >>