Optimization of Sodium Alginate-Chitosan Polyelectrolyte Complex for Enhanced Gastro-Resistant Performance of Diclofenac Sodium Microcapsules
Abstract
Diclofenac sodium (DS) is an effective nonsteroidal anti-inflammatory drug (NSAID) limited by a short half-life and gastric irritation. Microencapsulation with natural polymers enables gastric protection and controlled drug release. This study aims to formulate and optimize DS microcapsules using a combination of sodium alginate and chitosan polymers, with the addition of Tween 80, to achieve a gastro-resistant profile with ideal controlled release. The microcapsules were prepared using the ionotropic gelation method with varying concentrations of sodium alginate and chitosan: F1 (1.0%:0.05%), F2 (2.0%:0.1%), and F3 (3.0%:0.15%). Characterization included particle size analysis using a polarizing microscope, morphology using Scanning Electron Microscopy (SEM), entrapment efficiency (EE), and in vitro dissolution testing at various pH levels (1.2, 4.5, and 7.4). Data were analyzed using one-way ANOVA followed by Tukey’s post-hoc test to determine significant differences. F1 exhibited the best characteristics with a particle size of 221.42 ± 39.16 μm and the highest entrapment efficiency of 91.78%. The primary endpoint for gastro-resistance was successfully achieved by F1, showing a release of 9.71% at pH 1.2 for 120 minutes, meeting the compendial criterion of <10%. In contrast, F2 (13.17%) and F3 (17.88%) exceeded this limit with statistically significant differences (p<0.05). SEM image analysis confirmed that F1 had the smoothest and most compact surface with minimal porosity compared to the other formulations. This study demonstrates that optimizing the polymer concentration in F1 successfully created a compact polyelectrolyte complex matrix, effectively improved entrapment efficiency, and provided stable gastro-resistant protection for safer DS delivery.
Keywords
Full Text:
PDFReferences
L. Himiniuc et al., “Theoretical and experimental aspects of sodium diclofenac salt release from chitosan-based hydrogels and possible applications,” Gels, vol. 9, no. 5, art. no. 422, 2023. [Online]. Available: https://doi.org/10.3390/gels9050422
T. Mahmood et al., “Preparation, in vitro characterization, and evaluation of polymeric pH-responsive hydrogels for controlled drug release,” ACS Omega, vol. 9, no. 9, pp. 10498–10516, 2024. [Online]. Available: https://doi.org/10.1021/acsomega.3c08107
A. Amanullah et al., “Development and challenges of diclofenac-based novel therapeutics: Targeting cancer and complex diseases,” Cancers, vol. 14, no. 18, art. no. 4385, 2022. [Online]. Available: https://doi.org/10.3390/cancers14184385
M. Pooja, C. C. Kesavulu, J. V. Kumar, and Y. N. P., “Gastrointestinal perforations induced by long-term non-steroidal anti-inflammatory drug use: A case series analysis and discussion,” Int. J. Community Med. Public Health, vol. 11, no. 3, pp. 1339–1341, 2024. [Online]. Available: https://doi.org/10.18203/2394-6040.ijcmph20240641
M. A. S. Abourehab et al., “Alginate as a promising biopolymer in drug delivery and wound healing: A review of the state-of-the-art,” Int. J. Mol. Sci., vol. 23, no. 16, art. no. 9035, 2022. [Online]. Available: https://doi.org/10.3390/ijms23169035
D. Żakowiecki et al., “Development of a biphasic-release multiple-unit pellet system with diclofenac sodium using novel calcium phosphate-based starter pellets,” Pharmaceutics, vol. 13, no. 6, art. no. 805, 2021. [Online]. Available: https://doi.org/10.3390/pharmaceutics13060805
K. Trisopon, O. Kittipongpatana, N. Chomchoei, N. Yaowiwat, and P. Saokham, “Engineering large porous mannitol-PVA microparticles for extended drug delivery via spray drying,” Pharmaceutics, vol. 17, no. 9, art. no. 1135, 2025. [Online]. Available: https://doi.org/10.3390/pharmaceutics17091135
C. Yan and S.-R. Kim, “Microencapsulation for pharmaceutical applications: A review,” ACS Applied Bio Materials, 2024. [Online]. Available: https://doi.org/10.1021/acsabm.3c00776
N. I. Okafor, “Microencapsulation techniques in HIV pediatric formulations: Advances and future outlook,” Advances in Pharmacological and Pharmaceutical Sciences, vol. 2024, art. no. 5081655, 2024. [Online]. Available: https://doi.org/10.1155/2024/5081655
J. E. Aguilar-Toalá, D. Quintanar-Guerrero, A. Liceaga, and M. Zambrano-Zaragoza, “Encapsulation of bioactive peptides: A strategy to improve the stability, protect the nutraceutical bioactivity and support their food applications,” RSC Advances, vol. 12, pp. 6449–6458, 2022. [Online]. Available: https://doi.org/10.1039/D1RA08590E
L. E. Kurozawa and M. D. Hubinger, “Hydrophilic food compounds encapsulation by ionic gelation,” Current Opinion in Food Science, vol. 15, pp. 50–55, 2017. [Online]. Available: https://doi.org/10.1016/j.cofs.2017.06.004
J. Lai, A. K. Azad, W. Sulaiman, V. Kumarasamy, V. Subramaniyan, and S. A. Alshehade, “Alginate-based encapsulation fabrication technique for drug delivery: An updated review of particle type, formulation technique, pharmaceutical ingredient, and targeted delivery system,” Pharmaceutics, vol. 16, no. 3, art. no. 370, 2024. [Online]. Available: https://doi.org/10.3390/pharmaceutics16030370
H. Malektaj, A. D. Drozdov, and J. deClaville Christiansen, “Mechanical properties of alginate hydrogels cross-linked with multivalent cations,” Polymers, vol. 15, no. 14, art. no. 3012, 2023. [Online]. Available: https://doi.org/10.3390/polym15143012
J. M. M. Vidart, T. L. Silva, P. C. P. Rosa, M. G. A. Vieira, and M. G. C. Silva, “Development of sericin/alginate particles by ionic gelation technique for the controlled release of diclofenac sodium,” J. Appl. Polym. Sci., vol. 135, no. 12, art. no. 45919, 2018. [Online]. Available: https://doi.org/10.1002/app.45919
X. Wang et al., “Microencapsulating alginate-based polymers for probiotics delivery systems and their application,” Pharmaceuticals, vol. 15, no. 5, art. no. 644, 2022. [Online]. Available: https://doi.org/10.3390/ph15050644
A. Thakare, S. Sedani, S. Kriplani, A. Patel, and U. Umre, “Chitosan: A versatile biomaterial revolutionizing endodontic therapy,” Cureus, vol. 16, 2024. [Online]. Available: https://doi.org/10.7759/cureus.62506
J. Weng, A. Durand, and S. Desobry, “Chitosan-based particulate carriers: Structure, production and corresponding controlled release,” Pharmaceutics, vol. 15, no. 5, art. no. 1455, 2023. [Online]. Available: https://doi.org/10.3390/pharmaceutics15051455
R. D. Drăghici et al., “Diclofenac spongious matrices based on collagen and alginate for relieving injury pains,” in Proc. Int. Conf. Advanced Materials and Systems (ICAMS), 2018, pp. 75–80. [Online]. Available: https://doi.org/10.24264/icams-2018.I.10
S. A. Mardikasari, A. Suryani, N. I., and R. Indahyani, “Microencapsulation of mefenamic acid using chitosan and sodium alginate polymers by ionic gelation method,” Galenika Journal of Pharmacy, vol. 6, no. 2, pp. 192–203, 2020. [Online]. Available: https://doi.org/10.22487/j24428744.2020.v6.i2.14589
G. Bao, L. He, X. Zhang, X. Yu, J. Li, and D. Qin, “Preparation of 3-iodo-2-propargyl-butyl-carbamate-loaded microcapsules for long-term mold resistance in bamboo,” Polymers, vol. 17, no. 5, art. no. 679, 2025. [Online]. Available: https://doi.org/10.3390/polym17050679
H. Liu et al., “Preparation and thermal responsiveness of microencapsulated fluorinated liquids for automatic fire extinguishing,” Heliyon, vol. 10, no. 5, art. no. e27454, 2024. [Online]. Available: https://doi.org/10.1016/j.heliyon.2024.e27454
A. Vossoughi and H. W. T. Matthew, “Encapsulation of mesenchymal stem cells in glycosaminoglycans-chitosan polyelectrolyte microcapsules using electrospraying technique: Investigating capsule morphology and cell viability,” Bioengineering & Translational Medicine, vol. 3, no. 3, pp. 265–274, 2018. [Online]. Available: https://doi.org/10.1002/btm2.10111
A. M. Omer, M. S. Ahmed, G. M. El-Subruiti, R. E. Khalifa, and A. S. Eltaweil, “pH-sensitive alginate/carboxymethyl chitosan/aminated chitosan microcapsules for efficient encapsulation and delivery of diclofenac sodium,” Pharmaceutics, vol. 13, no. 3, art. no. 338, 2021. [Online]. Available: https://doi.org/10.3390/pharmaceutics13030338
Z. Fathalla, A. A. Fatease, and H. Abdelkader, “Formulation and in-vitro/ex-vivo characterization of pregelled hybrid alginate–chitosan microparticles for ocular delivery of ketorolac tromethamine,” Polymers, vol. 15, no. 13, art. no. 2773, 2023. [Online]. Available: https://doi.org/10.3390/polym15132773
R. Gao et al., “Advances in polysaccharide-based biopolymers for probiotic encapsulation: From single polysaccharides to composite systems,” Current Research in Food Science, vol. 11, art. no. 101186, 2025. [Online]. Available: https://doi.org/10.1016/j.crfs.2025.101186
S. Di Girolamo, C. Puorger, and G. Lipps, “Stable and selective permeable hydrogel microcapsules for high-throughput cell cultivation and enzymatic analysis,” Microbial Cell Factories, vol. 19, art. no. 185, 2020. [Online]. Available: https://doi.org/10.1186/s12934-020-01427-9
J. Anani, H. Noby, A. Zkria, T. Yoshitake, and M. Elkady, “Monothetic analysis and response surface methodology optimization of calcium alginate microcapsules characteristics,” Polymers, vol. 14, no. 4, art. no. 709, 2022. [Online]. Available: https://doi.org/10.3390/polym14040709
J. Hao, S. Yan, H. Yuan, C. Du, and Y. Tan, “High-strength alginate fibers wet-spun from pre-crosslinked sodium alginate solutions,” Carbohydrate Polymers, vol. 342, art. no. 122386, 2024. [Online]. Available: https://doi.org/10.1016/j.carbpol.2024.122386
J. Martinović et al., “Spray-drying microencapsulation of grape pomace extracts with alginate-based coatings and bioaccessibility of phenolic compounds,” Gels, vol. 11, no. 2, art. no. 130, 2025. [Online]. Available: https://doi.org/10.3390/gels11020130
M. Weyers, B. Peterson, J. Hamman, and J. Steenekamp, “Formulation of chitosan microparticles for enhanced intranasal macromolecular compound delivery: Factors that influence particle size during ionic gelation,” Gels, vol. 8, no. 11, art. no. 686, 2022. [Online]. Available: https://doi.org/10.3390/gels8110686
G. Toprakçı, İ. Toprakçı, and S. Şahin, “Alginate microbeads for trapping phenolic antioxidants in rosemary (Rosmarinus officinalis L.): Multivariate optimization based on bioactive properties and morphological measurements,” Gels, vol. 11, no. 3, art. no. 172, 2025. [Online]. Available: https://doi.org/10.3390/gels11030172
X. Han, S. Shao, X. Han, and Y. Zhang, “Preparation and characterization of methyl jasmonate microcapsules and their preserving effects on postharvest potato tuber,” Molecules, vol. 27, no. 15, art. no. 4728, 2022. [Online]. Available: https://doi.org/10.3390/molecules27154728
A. Kyzioł, A. Mazgała, J. Michna, A. Regiel-Futyra, and V. Sebastián, “Preparation and characterization of alginate/chitosan formulations for ciprofloxacin-controlled delivery,” J. Biomater. Appl., vol. 32, no. 2, pp. 162–174, 2017. [Online]. Available: https://doi.org/10.1177/0885328217714352
A. Gedawy, G. A. Di Luna, J. Martinez, D. Brown, H. Al-Salami, and C. Dass, “Novel silicone-grafted alginate as a drug delivery scaffold: Pharmaceutical characterization of gliclazide-loaded silicone-based composite microcapsules,” Pharmaceutics, vol. 15, no. 2, art. no. 530, 2023. [Online]. Available: https://doi.org/10.3390/pharmaceutics15020530
Y. Zhou, D. Xu, H. Yu, J. Han, W. Liu, and D. Qu, “Encapsulation of Salmonella phage SL01 in alginate/carrageenan microcapsules as a delivery system and its application in vitro,” Front. Microbiol., vol. 13, art. no. 906103, 2022. [Online]. Available: https://doi.org/10.3389/fmicb.2022.906103
K. Essifi et al., “Influence of sodium alginate concentration on microcapsules properties foreseeing the protection and controlled release of bioactive substances,” Journal of Chemistry, vol. 2021, art. no. 5531479, 2021. [Online]. Available: https://doi.org/10.1155/2021/5531479
A. Olea et al., “Formation and characterization of chitosan-based polyelectrolyte complex containing antifungal phenylpropanoids,” Polymers, vol. 16, no. 23, art. no. 3348, 2024. [Online]. Available: https://doi.org/10.3390/polym16233348
D. Bustos, L. Guzmán, O. Valdés, M. Muñoz-Vera, L. Morales-Quintana, and R. Castro, “Development and evaluation of cross-linked alginate–chitosan–abscisic acid blend gel,” Polymers, vol. 15, no. 15, art. no. 3217, 2023. [Online]. Available: https://doi.org/10.3390/polym15153217
N. Fülöpová, S. Pavloková, I. Debono, D. Vetchý, and A. Franc, “Development and comparison of various coated hard capsules suitable for enteric administration to small patient cohorts,” Pharmaceutics, vol. 14, no. 8, art. no. 1577, 2022. [Online]. Available: https://doi.org/10.3390/pharmaceutics14081577
R. W. Korsmeyer, R. Gurny, E. Doelker, P. Buri, and N. A. Peppas, “Mechanisms of solute release from porous hydrophilic polymers,” Int. J. Pharm., vol. 15, no. 1, pp. 25–35, 1983. [Online]. Available: https://doi.org/10.1016/0378-5173(83)90064-9
J. Siepmann and N. A. Peppas, “Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC),” Adv. Drug Deliv. Rev., vol. 48, no. 2–3, pp. 139–157, 2001. [Online]. Available: https://doi.org/10.1016/S0169-409X(01)00112-0
R. S. Özakar and E. Özakar, “The effect of polymer amount and crosslinker ratio in polymeric hydrogel beads on characterization,” Journal of Research in Pharmacy, vol. 25, no. 5, pp. 653–666, 2021. [Online]. Available: https://doi.org/10.29228/jrp.57
DOI: https://doi.org/10.37311/ijpe.v6i2.37951
Refbacks
- There are currently no refbacks.
Copyright (c) 2026 Hestiary Ratih, Alvyolian Bernard Manangsang, Jessie Sofia Pamudji, Nur Achsan Al-Hakim
Indonesian Journal of Pharmaceutical Education is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.