Sains Malaysiana 55(4)(2026): 645-657

http://doi.org/10.17576/jsm-2026-5504-05

 

Red Palm Oil Submicron Emulsions Formulated by D-Phase Emulsification: A D-Optimal Mixture Design Study Using Sucrose Palmitate and Glycerol

(Emulsi Submikron Minyak Sawit Merah Diformulasikan melalui Pengemulsian Fasa-D: Kajian Reka Bentuk Campuran D-Optimal menggunakan Sukrosa Palmitat dan Gliserol)

 

ELSA FITRIA APRIANI1, MAHDI JUFRI1,*, TOMMY JULIANTO BUSTAMI EFFENDI2,3, WINDY KEUMALA BUDIANTI4, NURZALINA ABDUL KARIM KHAN5, BUDIAWAN6 & ADILAH MARWA1

 

1Laboratory of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia

2Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia

3Department of Pharmacy Mitra Bunda Health Institute, Batam, 29454, Indonesia

4Department of Dermatology and Venereology, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National Central General Hospital, Jakarta, 10430, Indonesia

5Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia

6Department of Chemistry, Faculty of Sciences, Universitas Indonesia, Depok, 16424, Indonesia

 

Received: 2 June 2025/Accepted: 31 March 2026

 

Abstract

Red palm oil (RPO) contains carotenoids, which are highly beneficial to human health owing to their antioxidant properties. RPO has low stability during storage; hence, it must be formulated in a submicron emulsion. This study aims to enhance the formulation of RPO submicron emulsion using a D-phase emulsification method with D-optimal mixture design methodology. The effect of the concentration of RPO (45%-60%), sucrose palmitate (10%-25%), and glycerol (25%-40%) on globule size, polydispersity index (PDI), and zeta potential was investigated. The optimum formula was then subjected to a short-term accelerated stability test at 40 °C for 7 days, comparing the carotenoid retention in the submicron emulsion versus bulk RPO and characterized using Transmission Electron Microscopy (TEM) and Fourier Transform Infrared Spectroscopy (FTIR). The data showed that an increase in component concentrations below a preset limit resulted in a significant change in response cubically, thus yielding high coefficients of determination (R²>0.96) for all three responses (p<0.05). The optimum formula was achieved with components in the proportions of 55.70% RPO, 12.05% sucrose palmitate, and 32.25% glycerol, with globule size, PDI, and zeta potential of 184.20±2.75 nm, 0.079±0.011, and -40.40±0.53 mV, respectively. Notably, the short-term stability study showed that the submicron emulsion system significantly improved carotenoid stability compared to bulk RPO after 7 days at 40 °C. The TEM study confirmed that the emulsion globules form spheres and are uniformly distributed, whereas the FTIR study showed no chemical interactions. In summary, the D-phase emulsification method effectively produced a stable RPO submicron emulsion.

Keywords: D-optimal mixture design; D-phase emulsification; optimization; red palm oil; submicron emulsion

 

Abstrak

Minyak sawit merah (MSM) mengandungi karotenoid yang sangat bermanfaat untuk kesihatan manusia kerana sifat antioksidannya. MSM mempunyai kestabilan yang rendah semasa penyimpanan; oleh itu, ia mesti diformulasikan dalam emulsi submikron. Kajian ini bertujuan untuk meningkatkan formulasi emulsi submikron MSM menggunakan kaedah pengemulsian fasa-D dengan metodologi reka bentuk campuran D-optimum. Kesan kepekatan RPO (45%-60%), sukrosa palmitat (10%-25%) dan gliserol (25%-40%) ke atas saiz globul, PDI dan potensi zeta telah dikaji. Formula optimum kemudiannya tertakluk kepada ujian kestabilan dipercepatkan jangka pendek pada suhu 40 °C selama 7 hari, membandingkan pengekalan karotenoid dalam emulsi submikron berbanding MSM pukal dan dicirikan menggunakan Mikroskopi Elektron Pengimbasan (TEM) dan spektroskopi Fourier transformasi inframerah (FTIR). Data menunjukkan bahawa peningkatan kepekatan komponen di bawah had pratetap menyebabkan perubahan ketara dalam tindak balas secara kubik, dengan itu menghasilkan pekali penentuan yang tinggi (R²>0.96) untuk ketiga-tiga tindak balas (p<0.05). Formulasi terbaik dicapai dengan komponen dalam perkadaran 55.70% RPO, 12.05% sukrosa palmitat dan 32.25% gliserol dengan saiz globul, PDI dan potensi zeta masing-masing adalah 184.20±2.75 nm, 0.079±0.011 dan - 40.40±0.53 mV. Terutamanya, kajian kestabilan jangka pendek menunjukkan bahawa sistem emulsi submikron meningkatkan kestabilan karotenoid dengan ketara berbanding MSM pukal selepas 7 hari pada suhu 40 °C. Kajian TEM telah mengesahkan bahawa globul emulsi membentuk sfera dan diedarkan secara seragam, manakala kajian FTIR menunjukkan tiada interaksi kimia. Ringkasnya, kaedah pengemulsian fasa-D berkesan menghasilkan emulsi submikron MSM yang stabil.

Kata kunci: Emulsi submikron; minyak sawit merah; pengemulsian fasa D; pengoptimuman; reka bentuk campuran D-optimum

 

REFERENCES

Abd, E., Benson, H., Roberts, M. & Grice, J. 2018. Minoxidil skin delivery from nanoemulsion formulations containing eucalyptol or oleic acid: enhanced diffusivity and follicular targeting. Pharmaceutics 10(1): 19. https://doi.org/10.3390/pharmaceutics10010019

Abdul Wahab, R., Al-Obaidi, N.G., Yahya, N.A., Che Marzuki, N.H. & Mohd Bohari, S.P. 2022. Formulation of a stable water-in-oil nanoemulsion rich in anti-diabetic components of the roselle extract for controlled release. Chemical Papers 76(4): 2341-2356. https://doi.org/10.1007/s11696-021-02030-x

Almeida, L., Junior, J., Silva, M., Nóbrega, F., Andrade, J., Santos, W., Ribeiro, A., Conceição, M., Veras, G. & Medeiros, A.C. 2019. Tablet of Ximenia americana L. developed from mucoadhesive polymers for future use in oral treatment of fungal infections. Polymers 11(2): 379. https://doi.org/10.3390/polym11020379

Anarjan, N. & Tan, C.P. 2013. Effects of selected polysorbate and sucrose ester emulsifiers on the physicochemical properties of astaxanthin nanodispersions. Molecules 18(1): 768-777. https://doi.org/10.3390/molecules18010768

Apriani, E.F., Mardiyanto, M. & Hendrawan, A. 2022. Optimization of green synthesis of silver nanoparticles from Areca catechu L. seed extract with variations of silver nitrate and extract concentrations using simplex lattice design method. Farmacia 70(5): 917-924. https://doi.org/10.31925/farmacia.2022.5.18

Apriani, E.F., Shiyan, S., Hardestyariki, D., Starlista, V. & Febriani, M. 2023. Factorial design for the optimization of clindamycin HCl-loaded ethosome with various concentration of phospholipon 90G and ethanol. Research Journal of Pharmacy and Technology 16(4): 1561-1568. https://doi.org/10.52711/0974-360X.2023.00255

Ariyaprakai, S. & Tananuwong, K. 2015. Freeze thaw stability of edible oil-in-water emulsions stabilized by sucrose esters and Tweens. Journal of Food Engineering 152: 57-64. https://doi.org/10.1016/j.jfoodeng.2014.11.023

Barba, A.I.O., Hurtado, M.C., Mata, M.C.S., Ruiz, F. & de Tejada, M.L.S. 2006. Application of a UV–vis detection-HPLC method for a rapid determination of lycopene and beta-carotene in vegetables. Food Chemistry 95(2): 328-336. https://doi.org/10.1016/j.foodchem.2005.02.028

Chen, K., Yang, H., Xu, G., Hu, Y., Tian, X., Qin, S. & Jiang, T. 2025. Enhanced skin penetration of curcumin by a nanoemulsion-embedded oligopeptide hydrogel for psoriasis topical therapy. RSC Medicinal Chemistry 16(2): 961-969. https://doi.org/10.1039/d4md00781f

Chong, W.T., Tan, C.P., Cheah, Y.K., B. Lajis, A.F., Habi Mat Dian, N.L., Kanagaratnam, S. & Lai, O.M. 2018. Optimization of process parameters in preparation of tocotrienol-rich red palm oil-based nanoemulsion stabilized by Tween80-Span 80 using response surface methodology. PLoS ONE 13(8): e0202771. https://doi.org/10.1371/journal.pone.0202771

Ellison, S.L. 2015. Carotenoids: Physiology. In Encyclopedia of Food and Health, Elsevier. pp. 670-675. https://doi.org/10.1016/B978-0-12-384947-2.00120-3

Haddadzadegan, S., Dorkoosh, F. & Bernkop-Schnurch, A. 2022. Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers. Advanced Drug Delivery Reviews 182: 114097. https://doi.org/10.1016/j.addr.2021.114097

Henry, J.V., Fryer, P.J., Frith, W.J. & Norton, I.T. 2009. Emulsification mechanism and storage instabilities of hydrocarbon-in-water sub-micron emulsions stabilised with Tweens (20 and 80), Brij 96v and sucrose monoesters. Journal of Colloid and Interface Science 338(1): 201-206. https://doi.org/10.1016/j.jcis.2009.05.077

Lavanya, M., Namasivayam, S.K.R. & John, A. 2024. Developmental formulation principles of food preservatives by nanoencapsulation - Fundamentals, application, and challenges. Applied Biochemistry and Biotechnology 196(10): 7503-7533. https://doi.org/10.1007/s12010-024-04943-1

Lu, Y., Zhang, R., Jia, Y., Gao, Y. & Mao, L. 2023. Effects of nanoparticle types and internal phase content on the properties of W/O emulsions based on dual stabilization mechanism. Food Hydrocolloids 139: 108563. https://doi.org/10.1016/j.foodhyd.2023.108563

Mardiyanto, M., Apriani, E.F. & Helyken, F.P. 2023. The role of temperature and pH in the synthesis of silver nanoparticles using Areca catechu L. seed extract as bioreductor. Farmacia 71(2): 244-253. https://doi.org/10.31925/farmacia.2023.2.3

Miksusanti, Apriani, E.F. & Bihurini, A.H.B. 2023. Optimization of Tween 80 and PEG-400 concentration in Indonesian virgin coconut oil nanoemulsion as antibacterial against Staphylococcus aureus. Sains Malaysiana 52(4): 1259-1272. https://doi.org/10.17576/jsm-2023-5204-17

Mirhosseini, H. & Tan, C.P. 2009. Physicochemical properties of beverage emulsion as function of glycerol and vegetable oil contents. Journal of Food, Agriculture and Environment 7(3-4): 79-85.

Mundada, V., Patel, M. & Sawant, K. 2016. Submicron emulsions and their applications in oral delivery. Critical Reviews in Therapeutic Drug Carrier Systems 33(3): 265-308. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2016017218

Ozogul, Y., Karsli, G.T., Durmuş, M., Yazgan, H., Oztop, H.M., McClements, D.J. & Ozogul, F. 2022. Recent developments in industrial applications of nanoemulsions. Advances in Colloid and Interface Science 304: 102685. https://doi.org/10.1016/j.cis.2022.102685

Ping, B.T.Y., Idris, C.A.C. & Maurad, Z.A. 2020. Oxidative stability of refined red palm olein under two Malaysian storage conditions. Journal of Oleo Science 69(10): 1209-1218. https://doi.org/10.5650/jos.ess20045

Rao, J. & McClements, D.J. 2013. Optimization of lipid nanoparticle formation for beverage applications: Influence of oil type, cosolvents, and cosurfactants on nanoemulsion properties. Journal of Food Engineering 118(2): 198-204. https://doi.org/10.1016/j.jfoodeng.2013.04.010

Saberi, A.H., Fang, Y. & McClements, D.J. 2013. Effect of glycerol on formation, stability, and properties of vitamin-E enriched nanoemulsions produced using spontaneous emulsification. Journal of Colloid and Interface Science 411: 105-113. https://doi.org/10.1016/j.jcis.2013.08.041

Sharoni, Y., Linnewiel-Hermoni, K., Khanin, M., Salman, H., Veprik, A., Danilenko, M. & Levy, J. 2012. Carotenoids and apocarotenoids in cellular signaling related to cancer: A review. Molecular Nutrition & Food Research 56(2): 259-269. https://doi.org/10.1002/mnfr.201100311

Shu, M., Zhou, Y., Liu, Y., Fan, L. & Li, J. 2023. Sucrose esters and beeswax synergize to improve the stability and viscoelasticity of water-in-oil emulsions. Foods 12(18): 3387. https://doi.org/10.3390/foods12183387

Tan, C.H., Lee, C.J., Tan, S.N., Poon, D.T.S., Chong, C.Y.E. & Pui, L.P. 2021. Red palm oil: A review on processing, health benefits and its application in food. Journal of Oleo Science 70(9): 1201-1210. https://doi.org/10.5650/jos.ess21108

Tan, C.H., Ariffin, A.A., Ghazali, H.M., Tan, C.P., Kuntom, A. & Choo, A.C. 2017. Changes in oxidation indices and minor components of low free fatty acid and freshly extracted crude palm oils under two different storage conditions. Journal of Food Science and Technology 54(7): 1757-1764. https://doi.org/10.1007/s13197-017-2569-9

Vater, C., Hlawaty, V., Werdenits, P., Cichoń, M., Klang, V., Wirth, M. & Funding, C. 2020. Effects of lecithin-based nanoemulsions on skin: short-time cytotoxicity MTT and BrdU studies, skin penetration of surfactants and additives and the delivery of curcumin. International Journal of Pharmaceutics 580: 119209. https://doi.org/10.1016/j.ijpharm.2020.119209

Visetvichaporn, V., Kim, K.H., Jung, K., Cho, Y.S. & Kim, D.D. 2020. Formulation of self-microemulsifying drug delivery system (SMEDDS) by D-optimal mixture design to enhance the oral bioavailability of a new cathepsin K inhibitor (HL235). International Journal of Pharmaceutics 573: 118772. https://doi.org/10.1016/j.ijpharm.2019.118772

Wang, Y., Liang, X., Wang, Y. & Yu, H. 2017. Effects of viscosity index improver on morphology and graphitization degree of diesel particulate matter. Energy Procedia 105: 4236-4241. https://doi.org/10.1016/j.egypro.2017.03.910

Wilson, R., Li, Y., Yang, G. & Zhao, C. 2021. Nanoemulsions for drug delivery. Particuology 64: 85-97. https://doi.org/10.1016/j.partic.2021.05.009

Yukuyama, M.N., Oseliero, P.L.F., Kato, E.T.M., Lobënberg, R., de Oliveira, C.L.P., de Araujo, G.L.B. & Bou-Chacra, N.A. 2018. High internal vegetable oil nanoemulsion: D-phase emulsification as a unique low energy process. Colloids and Surfaces A: Physicochemical and Engineering Aspects 554: 296-305. https://doi.org/10.1016/j.colsurfa.2018.06.023

Zhang, Q., Shi, Y., Tu, Z., Hu, Y. & He, C. 2022. Emulsion properties during microencapsulation of cannabis oil based on protein and sucrose esters as emulsifiers: Stability and rheological behavior. Foods 11(23): 3923. https://doi.org/10.3390/foods11233923

Zhang, W., Qin, Y., Gao, Z., Ou, W., Zhu, H. & Zhang, Q. 2019. Phase behavior and stability of nano-emulsions prepared by D phase emulsification method. Journal of Molecular Liquids 285: 424-429. https://doi.org/10.1016/j.molliq.2019.04.112

 

*Corresponding author; email: mahdijufri@farmasi.ui.ac.id

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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