FORMULATION AND CHARACTERIZATION OF SAMBILOTO EXTRACT ORALLY DISSOLVING FILMS: A DUAL MECHANISM FOR PROBIOTIC GROWTH AND ANTIBACTERIAL ACTION

MIKSUSANTI MIKSUSANTI; ELSA FITRIA APRIANI; ADIK AHMADI; SHAUM SHIYAN; DINA PERMATA WIJAYA; VIO AGISTER RISANLI

doi:10.22159/ijap.2025v17i2.52902

Authors

MIKSUSANTI MIKSUSANTI Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia
ELSA FITRIA APRIANI Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia
ADIK AHMADI Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia
SHAUM SHIYAN Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia
DINA PERMATA WIJAYA Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia
VIO AGISTER RISANLI Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Indralaya, South Sumatra, Indonesia

DOI:

https://doi.org/10.22159/ijap.2025v17i2.52902

Keywords:

Antibacterial activity, Bifidobacterium longum, Nutraceutical, Orally dissolving films (ODF), Sambiloto extract

Abstract

Objective: This study aimed to develop Orally Dissolving Films (ODFs) containing Sambiloto leaf extract and evaluate their effects on the growth of the probiotic bacterium Bifidobacterium longum (B. longum) and their antibacterial activity against Escherichia coli (E. coli).

Methods: The ODFs were prepared using the solvent casting method with three concentrations: F1 (0.4%), F2 (0.6%), and F3 (0.8%). The growth of B. longum was assessed through the Total Plate Count method, while antibacterial activity was determined using the disc diffusion method.

Results: F2 was chosen as the optimal formulation, characterized by a smooth texture, a pH of 6.240±0.026, thickness of 0.102±0.008 mm, weight of 0.059±0.002 mg, disintegration time of 16.633±0.822 seconds, folding endurance of 433.00±2.000 folds, and elongation of 22.250±1.372%. F2 significantly enhanced the growth of B. longum, yielding 2.43×10¹⁰ CFU/ml and a prebiotic index of 1.056 (p<0.05). Additionally, it demonstrated antibacterial activity with an inhibition zone diameter of 7.500±0.408 mm (p<0.05).

Conclusion: This research highlights F2's potential as a nutraceutical product with both probiotic growth-enhancing and antibacterial properties.

References

Tadesse DA, Zhao S, Tong E, Ayers S, Singh A, Bartholomew MJ. Antimicrobial drug resistance in Escherichia coli from humans and food animals, United States, 1950-2002. Emerg Infect Dis. 2012;18(5):741-9. doi: 10.3201/eid1805.111153, PMID 22515968.

Bhatnagar A. A comprehensive review of Kalmegh's biological activities (Andrographis paniculata). Int J Pharm Pharm Sci. 2023;15(2):1-7. doi: 10.22159/ijpps.2023v15i2.46705.

Sharma P, Tomar SK, Goswami P, Sangwan V, Singh R. Antibiotic resistance among commercially available probiotics. Food Res Int. 2014;57:176-95. doi: 10.1016/j.foodres.2014.01.025.

Martinez FA, Balciunas EM, Converti A, Cotter PD, De Souza Oliveira RP. Bacteriocin production by Bifidobacterium spp. a review. Biotechnol Adv. 2013;31(4):482-8. doi: 10.1016/j.biotechadv.2013.01.010, PMID 23384878.

Mandal B. Bacteriocin. Int J Pharm Pharm Sci. 2024;16(3):1-7. doi: 10.22159/ijpps.2024v16i3.50326.

Yang L, Gao Y, Farag MA, Gong J, Su Q, Cao H. Dietary flavonoids and gut microbiota interaction: a focus on animal and human studies to maximize their health benefits. Food Front. 2023;4(4):1794-809. doi: 10.1002/fft2.309.

Chauhan ES, Sharma K, Bist R. Andrographis paniculata: a review of its phytochemistry and pharmacological activities. Res J Pharm Technol. 2019;12(2):891-900. doi: 10.5958/0974-360X.2019.00153.7.

Li Z, Ren Z, Zhao L, Chen L, Yu Y, Wang D. Unique roles in health promotion of dietary flavonoids through gut microbiota regulation: current understanding and future perspectives. Food Chem. 2023;399:133959. doi: 10.1016/j.foodchem.2022.133959, PMID 36001928.

Arikatla SK, Chalasani U, Mandava J, Yelisela RK. Interfacial adaptation and penetration depth of bioceramic endodontic sealers. J Conserv Dent. 2018;21(4):373-7. doi: 10.4103/JCD.JCD_64_18, PMID 30122816.

Shah KA, Gao B, Kamal R, Razzaq A, Qi S, Zhu QN. Development and characterizations of pullulan and maltodextrin-based oral fast-dissolving films employing a box–behnken experimental design. Materials (Basel). 2022;15(10):3591. doi: 10.3390/ma15103591, PMID 35629620.

Fong RJ, Robertson A, Mallon PE, Thompson RL. The impact of plasticizer and degree of hydrolysis on free volume of poly(vinyl alcohol) films. Polymers (Basel). 2018;10(9):1036. doi: 10.3390/polym10091036, PMID 30960961.

Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm. 2011;77(2):187-99. doi: 10.1016/j.ejpb.2010.11.023, PMID 21130875.

Hardestyariki D, Rasyid RS, Apriani EF. Sambiloto leaves (Andrographis paniculata (Burm.f.) Wall. Ex. Nees) nanoemulsion preparations: optimization of Tween 80 and PEG-400 concentrations as photoprotective agents. J Res Pharm. 2024;28(5):1435-48. doi: 10.29228/jrp.821.

Indarti K, Apriani EF, Wibowo AE, Simanjuntak P. Antioxidant activity of ethanolic extract and various fractions from green tea (Camellia sinensis L.) leaves. Pharmacogn J. 2019;11(4):771-6. doi: 10.5530/pj.2019.11.122.

Sudirman S, Herpandi SE, Safitri EF, Apriani EF, Taqwa FH. Total polyphenol and flavonoid contents and antioxidant activities of water lettuce (Pistia stratiotes) leave extracts. Food Res. 2022;6(4):205-10. doi: 10.26656/fr.2017.6(4).484.

Idorenyin E, Ekpenyong E, James I, Ibuot A. Antimicrobial properties of Andrographis paniculata (vinegar) leaf on selected human pathogens. World J Bio Pharm Health Sci. 2020;3(1):60-5. doi: 10.30574/wjbphs.2020.3.1.0047.

Shah KA, Gao B, Kamal R, Razzaq A, Qi S, Zhu QN. Development and characterizations of pullulan and maltodextrin-based oral fast-dissolving films employing a box–behnken experimental design. Materials (Basel). 2022;15(10):3591. doi: 10.3390/ma15103591, PMID 35629620.

Palezi SC, Fernandes SS, Martins VG. Oral disintegration films: applications and production methods. J Food Sci Technol. 2023;60(10):2539-48. doi: 10.1007/s13197-022-05589-9, PMID 37599841.

Owolabi IO, Dat-arun P, Takahashi Yupanqui C, Wichienchot S. Gut microbiota metabolism of functional carbohydrates and phenolic compounds from soaked and germinated purple rice. J Funct Foods. 2020;66:103787. doi: 10.1016/j.jff.2020.103787.

Liu Q, Liu Y, Li F, Gu Z, Liu M, Shao T. Probiotic culture supernatant improves metabolic function through FGF21-adiponectin pathway in mice. J Nutr Biochem. 2020;75:108256. doi: 10.1016/j.jnutbio.2019.108256, PMID 31760308.

Fitria Apriani E, Shiyan S, Hardestyariki D, Starlista V, Laras Sari A. Optimization of hydroxypropyl methylcellulose (HPMC) and carbopol 940 in clindamycin HCl ethosomal gel as anti-acne. Res J Pharm Technol. 2024;17(2):603-11. doi: 10.52711/0974-360X.2024.00094.

Mardiyanto M, Apriani EF, Hafizhaldi Alfarizi MH. Formulation and in vitro antibacterial activity of gel containing ethanolic extract of purple sweet potato leaves (Ipomoea batatas (L.) loaded poly lactic co-glycolic acid submicroparticles against staphylococcus aureus. Res J Pharm Technol. 2022;15(8):3599-605. doi: 10.52711/0974-360X.2022.00603.

Miksusanti M, Elsa Fitria Apriani EF, Bama Bihurinin AH. Optimization of tween 80 and PEG-400 concentration in Indonesian virgin coconut oil nanoemulsion as antibacterial against Staphylococcus aureus. Sains Malays. 2023;52(4):1259-72. doi: 10.17576/jsm-2023-5204-17.

Thonte SS, Bachipale RR, Pentewar RS, Gholve SB, Bhusnure OG. Formulation and evaluation of oral fast dissolving film of levosalbutamol sulphate. World J Pharm Res. 2017;4:1298-318.

Luo Z, Murray BS, Ross AL, Povey MJ, Morgan MR, Day AJ. Effects of pH on the ability of flavonoids to act as pickering emulsion stabilizers. Colloids Surf B Biointerfaces. 2012;92:84-90. doi: 10.1016/j.colsurfb.2011.11.027, PMID 22197223.

Hoque M, Alam M, Wang S, Zaman JU, Rahman MS, Johir M. Interaction chemistry of functional groups for natural biopolymer-based hydrogel design. Materials Science and Engineering R: Reports. 2023;156. doi: 10.1016/j.mser.2023.100758.

Cupone IE, Sansone A, Marra F, Giori AM, Jannini EA. Orodispersible film (ODF) platform based on maltodextrin for therapeutical applications. Pharmaceutics. 2022;14(10):2011. doi: 10.3390/pharmaceutics14102011, PMID 36297447.

Malipeddi VR, Awasthi R, Ghisleni DD, de Souza Braga M, Kikuchi IS, de Jesus Andreoli Pinto T. Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system. Drug Deliv Transl Res. 2017;7(1):66-76. doi: 10.1007/s13346-016-0334-7, PMID 27677866.

Cardona F, Andres Lacueva C, Tulipani S, Tinahones FJ, Queipo Ortuno MI. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24(8):1415-22. doi: 10.1016/j.jnutbio.2013.05.001, PMID 23849454.

Kemperman RA, Bolca S, Roger LC, Vaughan EE. Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities. Microbiology (Reading). 2010;156(11):3224-31. doi: 10.1099/mic.0.042127-0, PMID 20724384.

Hong L, Kim WS, Lee SM, Kang SK, Choi YJ, Cho CS. Pullulan nanoparticles as prebiotics enhance the antibacterial properties of Lactobacillus plantarum through the induction of mild stress in probiotics. Front Microbiol. 2019;10:142. doi: 10.3389/fmicb.2019.00142, PMID 30787918.

Savitskaya I, Zhantlessova S, Kistaubayeva A, Ignatova L, Shokatayeva D, Sinyavskiy Y. Prebiotic cellulose-pullulan matrix as a “vehicle” for probiotic biofilm delivery to the host large intestine. Polymers (Basel). 2023;16(1):30. doi: 10.3390/polym16010030, PMID 38201695.

Hossain S, Urbi Z, Karuniawati H, Mohiuddin RB, Moh Qrimida AM, Allzrag AM. Andrographis paniculata (Burm. f.) wall. Ex nees: an updated review of phytochemistry, antimicrobial pharmacology, and clinical safety and efficacy. Life (Basel). 2021;11(4):348. doi: 10.3390/life11040348, PMID 33923529.

Facchin S, Bertin L, Bonazzi E, Lorenzon G, De Barba C, Barberio B. Short-chain fatty acids and human health: from metabolic pathways to current therapeutic implications. Life (Basel). 2024;14(5):559. doi: 10.3390/life14050559, PMID 38792581.

Zhang D, Jian YP, Zhang YN, Li Y, Gu LT, Sun HH. Short-chain fatty acids in diseases. Cell Commun Signal. 2023;21(1):212. doi: 10.1186/s12964-023-01219-9, PMID 37596634.

Anjana TSK. Bacteriocin-producing probiotic lactic acid bacteria in controlling dysbiosis of the gut microbiota. Front Cell Infect Microbiol. 2022;12:1-11. doi: 10.3389/fcimb.2022.85114033.

Yu D, Pei Z, Chen Y, Wang H, Xiao Y, Zhang H. Bifidobacterium longum subsp. infantis as widespread bacteriocin gene clusters carrier stands out among the Bifidobacterium. Appl Environ Microbiol. 2023;89(9):e0097923. doi: 10.1128/aem.00979-23, PMID 37681950.