OPTIMIZATION OF SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) FORMULA OF COMBINED 70% ETHANOLIC EXTRACT OF BENALU BATU (BEGONIA MEDICINALIS) HERBS AND KELOR (MORINGA OLEIFERA L.) LEAVES USING SIMPLEX LATTICE DESIGN METHOD
DOI:
https://doi.org/10.22159/ijap.2025v17i1.52165Keywords:
Begonia medicinalis, Moringa oleifera, SNEDDS, Simplex lattice design, HeLa cellsAbstract
Objective: This research aims to perform Self Nano-Emulsifying Drug Delivery System (SNEDDS) formulation of combined ethanolic extract of benalu batu (Begonia medicinalis) herbs and kelor (Moringa oleifera) leaves, determine the optimal concentration based on physicochemical characteristics as well as the phytochemical contents and in vitro anticancer activity.
Methods: Surfactant and co-surfactant concentrations were determined by Design Expert v.13 software with Simplex Lattice Design (SLD) method. The phytochemical contents were measured by using a UV-Vis spectrophotometer, and the inhibition activity on HeLa cancer cells was tested by using the MTT method.
Results: Design Expert with the SLD method produces five design formulas. The most optimal SNEDDS formula based on the SLD method was formula 5, which contains a combination of extract of benalu batu herbs and kelor leaves with a concentration ratio of 1:1 (100 mg :100 mg), 12% Virgin Coconut Oil (VCO), 64% tween 80, and 16% propylene glycol. The optimal formula has the characteristics of an emulsification time of 39.30 ± 3.055 seconds, a transmittance percentage of 92.25% ± 0.004, a particle size of 14.43 nm ± 0.306 with a Polydispersity Index (PI) of 0.237, pH of 4.70 ± 0.031 and viscosity of 355 cps ± 2.6. It also contains total phenolic content of 5.517 ± 0.382 mg/g GAE, total flavonoids of 8.501 ± 0.695 mg/g QE, and total saponins of 17.991 ± 0.052 mg/g EE. In addition, it also possesses a high percentage of cell death of Hela cancer, which is 84.334% at a concentration of 200 µg/ml.
Conclusion: Formula 5 has the potential for anticancer activity with good characteristics as SNEDDS formula.
Downloads
References
Maulana S, Wahyuni TS, Widiyanti P, Zubair MS. In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors. Journal of Public Health in Africa. 2023;14(Suppl 1).
Zubair MS, Alarif WM, Ghandourah MA, Anam S, Jantan I. Cytotoxic activity of 2-o-β-glucopyranosil cucurbitacin d from benalu batu (Begonia sp.) growing in Morowali, Central Sulawesi. Indones J Chem. 2020;20(4):766-72.
Zubair MS, Anam S, Ritna A, Dwimurti F, Rismayanti D. Cytotoxic Activity of Benalu Batu (Begonia sp.) Methanolic Extract: An Ethnomedicine of Wana Tribe Central Sulawesi. Indonesian Journal of Pharmaceutical Sciences. 2018;12(1):10-6.
Lakshminarayana M, Shivkumar H, Rimaben P, Bhargava V. Antidiarrhoeal activity of leaf extract of Moringa oleifera in experimentally induced diarrhoea in rats. International journal of Phytomedicine. 2011;3(1):68.
Sulastri E, Zubair MS, Anas NI, Abidin S, Hardani R, Yulianti R. Total phenolic, total flavonoid, quercetin content and antioxidant activity of standardized extract of Moringa oleifera leaf from regions with different elevation. Pharmacognosy journal. 2018;10(6s).
Zubair MS, Syamsidi A, Sulastri E, Rahman A, Widyasari N, Pakaya D. Immunomodulatory Activity of Begonia medicinalis Ethanolic Extract in Experimental Animals. Indonesian Journal of Pharmacy. 2022:575–82-–82.
O'Shea JP, Augustijns P, Brandl M, Brayden DJ, Brouwers J, Griffin BT, et al. Best practices in current models mimicking drug permeability in the gastrointestinal tract-An UNGAP review. Eur J Pharm Sci. 2022;170:106098.
Bhalani DV, Nutan B, Kumar A, Singh Chandel AK. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines. 2022;10(9):2055.
Ammar HO, El-Feky GS, Ali AMA, Dawood RAG. Enhancement of oral bioavailability of repaglinide by self-nanoemulsifying drug delivery system. Int J Pharm Pharm Sci. 2014;6:603-6.
Mathew R, Varkey J. Formulation and in vitro evaluation of self nano emulsifying drug delivery system of quercetin for enhancement of oral bioavailability. Int J Curr Pharm Sci. 2022;14(1):60-9.
Annisa R, Mutiah R, Yuwono M, Hendradi E. Nanotechnology Approach-Self Nanoemulsifying Drug Delivery System (SNEDDS). Int J App Pharm. 2023;15(4):12-9.
Beandrade MU. Formulation and characterization of SNEDDS of black cumin (Nigella sativa) extract with shark fin fish oil phase (Centrophorus sp) and immunostimulant activity test. Journal of Pharmaceutical Science and Clinical Research. 2018;1(5):234-44.
Astuti IY, Marchaban M, Martien R, Nugroho AE. Design and Optimization of Self Nano-Emulsifying Drug Delivery System Containing a New Anti-inflamatory Agent Pentagamavunon-0. Indones J Chem. 2017;17(3):365-75.
Sopyan I, Gozali D, Kurniawansyah I, Guntina R. Design-expert software (DOE): An application tool for optimization in pharmaceutical preparations formulation. Int J App Pharm. 2022;14(4):55-63.
Utami IK. Optimization and Characterization of Formulation Self-Nanoemulsifying Drug Delivery System Ethanol Extract of Romang Parang Leaves (Boehmeria virgata). Asian J Pharm Clin Res. 2021:207-12.
Gohel M, Purohit A, Patel A, Hingorani L. Optimization of bacoside a loaded snedds using d-optimal mixture design for enhancement insolubility and bioavailability. Int J Pharm Pharm Sci. 2016:213-20.
Sandhu PS, Kumar R, Beg S, Jain S, Kushwah V, Katare O, Singh B. Natural lipids enriched self-nano-emulsifying systems for effective co-delivery of tamoxifen and naringenin: systematic approach for improved breast cancer therapeutics. Nanomedicine: Nanotechnology, Biology and Medicine. 2017;13(5):1703-13.
Fitria A, Hanifah S, Chabib L, Uno AM, Munawwarah H, Atsil N, et al. Design and characterization of propolis extract loaded self-nano emulsifying drug delivery system as immunostimulant. Saudi Pharm J. 2021;29(6):625-34.
Annisa R, Yuwono M, Hendradi E. Effect of vegetable oil on self-nanoemulsifying drug delivery system of Dayak Onion [Eleutherine palmifolia (L.) Merr.] extract using hydrophilic-lipophilic balance approach: formulation, characterization. International Journal of Drug Delivery Technology. 2020;10(2):210-6.
Sulkhan AAR, Artanti AN, Ermawati DE, Prihapsara F, editors. Optimization of Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Annona muricata L. leaves chloroform extract using VCO (Virgin Coconut Oil) as an oil phase. IOP Conference Series: Materials Science and Engineering; 2019: IOP Publishing.
Ermawati DE, Surya AP, Yugatama A. Characterization of Nanosilver Biosynthesis by Citrus sinensis (L.) Osbeck and Peel-off Mask Formulation with Variation Polyethylene Glycol 400-Glycerin Concentration. Indonesian Journal of Pharmaceutical Science and Technology. 2021;1:47-56.
Kim JS, ud Din F, Lee SM, Kim DS, Choi YJ, Woo MR, et al. Comparative study between high-pressure homogenisation and Shirasu porous glass membrane technique in sildenafil base-loaded solid SNEDDS: effects on physicochemical properties and in vivo characteristics. Int J Pharm. 2021;592:120039.
Sahumena MH, Suryani S, Rahmadani N. Self-Nanoemulsifying Drug Delivery System (SNEDDS) formulation of mefenamic acid using VCO with a combination of tween and span surfactants. Journal Syifa Sciences and Clinical Research (JSSCR). 2019;1(2):37-46.
Nirmalayanti NLPKV. Screening of Various Types of Surfactants and Cosurfactants as a Basis for Selecting Nanoemulsion Formulations. Metta: Jurnal Ilmu Multidisiplin. 2021;1(3):158-66.
Zhao Y, Wang C, Chow AH, Ren K, Gong T, Zhang Z, Zheng Y. Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of Zedoary essential oil: formulation and bioavailability studies. Int J Pharm. 2010;383(1-2):170-7.
Ermawati DE, Wulandari W, Yugatama A. Optimization of olive oil, tween 80, and propylene glycol of selfnanoemulsifying drug delivery system of zinc oxide by D-optimal method. Journal of Pharmaceutical Sciences and Community. 2020;17(2):92-101.
Bali V, Ali M, Ali J. Study of surfactant combinations and development of a novel nanoemulsion for minimising variations in bioavailability of ezetimibe. Colloids Surf B Biointerfaces. 2010;76(2):410-20.
Salem HF, Kharshoum RM, Sayed OM, Abdel Hakim LF. Formulation development of self-nanoemulsifying drug delivery system of celecoxib for the management of oral cavity inflammation. J Liposome Res. 2019;29(2):195-205.
Xi J, Chang Q, Chan CK, Meng ZY, Wang GN, Sun JB, et al. Formulation development and bioavailability evaluation of a self-nanoemulsified drug delivery system of oleanolic acid. AAPS PharmSciTech. 2009;10:172-82.
Saryanti D, Setiawan I. Optimization of Selfnanoemulsifying Drug Delivery System (SNEDDS) Formulation of Ethil Acetate Fraction Soursop Leaf as Antioxidant. Indonesian Journal of Global Health Research. 2022;4(3):559-66.
Bandyopadhyay S, Katare O, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces. 2012;100:50-61.
Zhao T. Self-nanoemulsifying drug delivery systems (SNEDDS) for the oral delivery of lipophilic drugs. 2015.
Szymczak J, Cielecka-Piontek J. Fisetin—In search of better bioavailability—From macro to nano modifications: A review. Int J Mol Sci. 2023;24(18):14158.
Syukri Y, Afetma D, Sirin M, Fajri R, Ningrum A, Setiawan S, Wibowo A. Validation of a simple HPLC-UV method for the quantification of andrographolide in self-nano emulsifying drug delivery system (SNEDDS) for dissolution study. Int J Drug Deliv Technol. 2017;7:239-43.
Al-Asmari AK, Albalawi SM, Athar MT, Khan AQ, Al-Shahrani H, Islam M. Moringa oleifera as an anti-cancer agent against breast and colorectal cancer cell lines. PloS one. 2015;10(8):e0135814.
Published
How to Cite
Issue
Section
Copyright (c) 2024 MUHAMMAD SULAIMAN ZUBAIR, JUSRIANI, EVI SULASTRI, ARMINI SYAMSIDI, ARWANSYAH
This work is licensed under a Creative Commons Attribution 4.0 International License.