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All Journal MPI (Media Pharmaceutica Indonesiana) Science and Technology Indonesia Jurnal Farmasi Galenika
Winantari, Agnes Nuniek
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Biochemistry, Genetics & Molecular Biology Chemical Engineering, Chemistry & Bioengineering Chemistry Environmental Science Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Physics Public Health

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Journal : Science and Technology Indonesia

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Enhancing In Vitro Dissolution of Ferulic Acid Through Co-Crystal Formation Using Malonic Acid and Nicotinamide Co-formers Setyawan, Dwi; Soraya, Yasmin; Ekowati, Juni; Winantari, Agnes Nuniek; Rani, Karina Citra; Kanzaffa, Firly Afnauriza Tedja; Pujiono, Ferry Eko
Science and Technology Indonesia Vol. 10 No. 4 (2025): October
Publisher : Research Center of Inorganic Materials and Coordination Complexes, FMIPA Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26554/sti.2025.10.4.1255-1269

Abstract

Ferulic acid is categorized as a Biopharmaceutical Classification System (BCS) class II drug, which exhibits low solubility in water (0.91 mg/mL). The formation of a co-crystal using malonic acid and nicotinamide as co-formers by the microwave irradiation method is an approach to enhance its solubility and dissolution. This study aims to evaluate the effect of co-crystal formation using these two co-formers at a 1:1 molar ratio on the solubility and dissolution of ferulic acid. The result emphasizes the formation of new peaks and peak shifting compared to the pure materials characterized from the Fourier Transform Infrared (FT-IR) spectrum. Moreover, the Differential Scanning Calorimetry (DSC) thermogram exhibits the differences in the co-crystal melting point compared to the pure drug and co-former, indicating the alteration of molecular structure on the crystal lattice of ferulic acid caused by the strong interaction between supramolecular homomer and heteromeric synthon. The formation of a new crystalline phase is also observed from the X-ray Diffraction (XRD) diffractogram, suggesting the formation of a different phase from its co-crystal component. The morphology characterization using Scanning Electron Microscope (SEM) revealed that the ferulic acid crystal habit changes into different forms, which is acclaimed as a co-crystal formation. The results of this study also disclosed that the co-crystal formation of ferulic acid significantly enhances ferulic acid solubility and dissolution characteristics compared to the pure drug and physical mixture (p < 0.05). The enhancement of solubility is 11.85% and 10.39% for ferulic acid–malonic acid and ferulic acid–nicotinamide co-crystal, respectively. Moreover, the dissolution rate of ferulic acid increases 3.50-fold and 3.61-fold from the formation of those co-crystals. Therefore, the formation of ferulic acid–malonic acid as well as ferulic acid–nicotinamide co-crystals in a 1:1 molar ratio by the microwave irradiation method is effective in improving ferulic acid solubility and dissolution.
Computational Chemical Interactions Study and Characterization of Rutin-Malic Acid and Rutin-Nicotinamide Binary Mixture by Microwave Irradiation Winantari, Agnes Nuniek; Dewantara, Djayawati Poetri; Sumartha, I Gede Ari; Rani, Karina Citra; Pradana, Aditya Trias; Kesuma, Dini
Science and Technology Indonesia Vol. 11 No. 1 (2026): January
Publisher : Research Center of Inorganic Materials and Coordination Complexes, FMIPA Universitas Sriwijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26554/sti.2026.11.1.196-206

Abstract

Rutin is a saf flavonol glycoside with potent antioxidant activities. However, its low water solubility (122.6–126 μg/mL) limits rutin applications. Binary mixtures of rutin–malic acid (R-MA) and rutin–nicotinamide (R-NIC) are among the strategies used to improve rutin’s solubility. This research aimed to evaluate the chemical interactions and physical characteristics of both binary mixtures (in equimolar ratios). The chemical interactions of R-MA and R-NIC were studied using the molecular docking method (AutoDock4). The results showed that the lowest binding energies of R-MA and R-NIC were −1.18 kcal/mol and −2.77 kcal/mol, respectively, with evidence of hydrogen bonding and π–π stacking interactions. The binary mixtures of R-MA (1:1) and R-NIC (1:1) were prepared by the microwave irradiation method. R-MA (1:1) and R-NIC (1:1) were prepared by slurrying under continuous stirring at 120 rpm, 70 °C for 4 min, and the microwave irradiation energy was set to 300 Watt for 5 min of exposure time. The formed binary mixture physical characteristics were evaluated using PXRD, DSC, FTIR, and SEM. The characterization results indicated the presence of a binary mixture. Compared to the physical mixture and their parent components (rutin, MA/NIC), diffractograms, thermograms, and IR spectrums respectively showed that the binary mixture has similar crystallinity profiles, decreased endothermic peaks, and not significantly shifted wavenumbers. Morphology analysis depicted that rutin, MA, and NIC are acicular, plate, and columnar shaped, respectively, while both binary mixtures showed an agglomerated fine needle-like, irregular shape, and rough-surface particles. This research shows that the binary mixtures of R-MA and R-NIC were successfully formed using this method, in accordance with chemical interaction predictions.
Co-Authors Aditya Trias Pradana Arina Swastika Maulita, Arina Swastika Dewantara, Djayawati Poetri Dwi Setyawan I Gede Ari Sumartha Juni Ekowati Kanzaffa, Firly Afnauriza Tedja Kesuma, Dini Pujiono, Ferry Eko Rani, Karina Citra Rizky , Astridani Soraya, Yasmin Tjioe, Felicia Reynaldo