Aktivitas Antibakteri Kokristal Sefiksim-Nikotinamida Menggunakan Agar Diffusion dan Broth Dilution Test

Authors

Abstract

Sefiksim telah berhasil dibuat dalam bentuk kokristal dengan nikotinamida (koformer). Kokristal SEF-NIK dibuat dengan perbandingan mol 1:1 menggunakan metode liquid-assisted grinding­. Kokristal dikarakterisasi menggunakan DSC, FTIR, SEM, dan PXRD. Hasil karakterisasi menunjukkan bahwa terbentuk kokristal antara sefiksim dan nikotinamida. Hasil uji kelarutan, laju disolusi, dan permeabilitas kokristal SEF-NIK menunjukkan peningkatan yang signifikan dibandingkan dengan sefiksim murni. Berdasarkan hasil penelitian tersebut, kokristal SEF-NIK dilanjutkan ke tahap uji farmakodinamik yakni uji aktivitas antibakteri secara in vitro. Penelitian ini bertujuan untuk mengetahui pengaruh dari teknik kokristalisasi terhadap aktvitas antibakteri sefiksim. Pengujian dilakukan menggunakan dua metode yakni Agar Diffusion Method (difusi agar) dan Broth Dilution Method (dilusi cair). Hasil penelitian menunjukkan bahwa kokristalisasi sefiksim dengan nikotinamida tidak menghambat efektivitasnya terhadap bakteri Escherichia coli, akan tetapi efektivitasnya lebih baik dibandingkan sefiksim murni. Pada metode difusi agar, zona hambat sefiksim terhadap bakteri Escherichia coli sebesar 6,2 mm sedangkan kokristal SEF-NIK lebih besar yakni 8,6 mm. Pada metode dilusi cair, hasil pengukuran OD bakteri Escherichia coli hari kelima pada sefiksim sebesar 1,330 sedangkan pada kokristal SEF-NIK sebesar 1,064.

References

Abdullah, A., Mutmainnah, Sangkal, A., & Ismail, R. (2022). UV-Vis Spectrophotometric Method Validation of Cefixime in Phosphate Buffer. Lumbung Farmasi: Jurnal Ilmu Kefarmasian, 3(2), 144–147. https://doi.org/10.31764/lf.v3i2.7657

Arora, S. C., Sharma, P. K., Irchhaiya, R., Khatkar, A., Singh, N., & Gagoria, J. (2010). Development, Characterization, and Solubility Study of Solid Dispersion of Cefixime Trihydrate by Solvent Evaporation Method. International Journal of Drug Development and Research, 2(2), 230–424. https://doi.org/10.4103/0110-5558.72427

Kawabata, Y., Wada, K., Nakatani, M., Yamada, S., & Onoue, S. (2011). Formulation Design for Poorly Water-Soluble Drugs Based on Biopharmaceutics Classification System: Basic Approaches and Practical Applications. International Journal of Pharmaceutics, 420, 1–10. https://doi.org/10.1016/j.ijpharm.2011.08.032

Korotkova, E. I., & Kratochvíl, B. (2014). Pharmaceutical Cocrystals. Procedia Chemistry, 10, 473–476.

Abdullah, A., Mutmainnah, & Wikantyasning, E. R. (2022). Cocrystals of Cefixime with Nicotinamide: Improved Solubility, Dissolution, and Permeability. Indonesian Journal of Pharmacy, 33(3), 394–400. https://doi.org/10.22146/ijp.2530

Savjani, K. T., Gajjar, A. K., & Savjani, J. K. (2012). Drug Solubility: Importance and Enhancement Techniques. ISRN Pharmaceutics.

Shaikh, M. I., Derle, N. D., & Bhamber, R. (2012). Permeability Enhancement Techniques for Poorly Permeable Drugs: A Review. Journal of Applied Pharmaceutical Science, 2(6), 34–39.

Qiao, N., Li, M., Schlindwein, W., Malek, N., Davies, A., & Trappitt, G. (2011). Pharmaceutical Cocrystals: An Overview. International Journal of Pharmaceutics, 419, 1–11.

Vasisht, K., Chadha, K., Karan, M., Bhalla, Y., Jena, A. K., & Chadha, R. (2016). Enhancing Biopharmaceutical Parameters of Bioflavonoid Quercetin by Cocrystallization. CrystEngComm, 18(8), 1403–1415. https://doi.org/10.1039/c5ce01899d

Vasisht, K., Chadha, K., Karan, M., Bhalla, Y., Chadha, R., Khullar, S., & Mandal, S. (2017). Co-crystals of Hesperitin: Structural, Pharmacokinetic, and Pharmacodynamic Evaluation. Crystal Growth & Design, 17(5), 2386–2405. https://doi.org/10.1021/acs.cgd.6b01769

Tomar, S., Chakraborti, S., Jindal, A., Grewal, M. K., & Chadha, R. (2020). Cocrystals of Diacerein: Towards the Development of Improved Biopharmaceutical Parameters. International Journal of Pharmaceutics, 574. https://doi.org/10.1016/j.ijpharm.2019.118942

Shemchuk, O., D’Agostino, S., Fiore, C., Sambri, V., Zannoli, S., Grepioni, F., & Braga, D. (2020). Natural Antimicrobials Meet a Synthetic Antibiotic: Carvacrol-thymol and Ciprofloxacin Cocrystals as A Promising Solid-State Route to Activity Enhancement. Crystal Growth and Design, 20(10), 6796–6803. https://doi.org/10.1021/acs.cgd.0c00900

Wang, L. Y., Bu, F. Z., Li, Y. T., Wu, Z. Y., & Yan, C. W. (2020). A Sulfathiazole-Amantadine Hydrochloride Cocrystal: The First Codrug Simultaneously Comprising Antiviral and Antibacterial Components. Crystal Growth and Design, 20(5), 3236–3246. https://doi.org/10.1021/acs.cgd.0c00075

Oxoid. (n.d.). Mueller Hinton Agar. Retrieved September 5, 2023, from http://www.oxoid.com/UK/blue/prod_detail/prod_detail.asp?pr=CM0337&c=UK&lang=EN

Merck. (n.d.). Nutrient Broth. Retrieved September 5, 2023, from https://www.merckmillipore.com/ID/id/product/Nutrient-broth,MDA_CHEM-105443?ReferrerURL=https%3A%2F%2Fwww.bing.com%2F#anchor_TI

Balouiri, M., Sadiki, M., & Ibnsouda, S. K. (2016). Methods for In Vitro Evaluating Antimicrobial Activity: A Review. Journal of Pharmaceutical Analysis, 6(2), 71–79. https://doi.org/10.1016/j.jpha.2015.11.005

Azizah, A. N., Ichwanuddin, & Marfu’ah, N. (2020). Aktivitas Antibakteri Ekstrak Etanol Teh Hijau (Camellia sinensis) terhadap Pertumbuhan Staphylococcus epidermidis. Pharmaceutical Journal of Islamic Pharmacy, 4(2), 15–23. https://doi.org/10.21111/pharmasipha.v4i2.4158

Buch, T., & Rollová, B. M. (2019). Bacterial Growth Curve by OD600 and SoloVPE. In Biofactory Competence Centre.

Matlock, B. C. (2019). Differences in Bacterial Optical Density Measurements Between UV-Visible Spectrophotometers. In Technical Note (Issue 52236).

Schultheiss, N., & Newman, A. (2009). Pharmaceutical Cocrystals and Their Physicochemical Properties. Crystal Growth and Design, 9(6), 2950–2967.

Kumar, S., & Nanda, A. (2017). Pharmaceutical Cocrystals: An Overview. Indian Journal of Pharmaceutical Sciences, 79(6), 858–871. https://doi.org/10.4172/pharmaceutical-sciences.1000302

Bunaciu, A. A., Udristioiu, elena gabriela, & Aboul-Enein, H. Y. (2015). X-Ray Diffraction: Instrumentation and Applications. Critical Reviews in Analytical Chemistry, 45, 289–299.

Brittain, H. G. (2012). Cocrystal Systems of Pharmaceutical Interest: 2010. Crystal Growth & Design, 12, 1046–1054.

Muhammad, A., Nurulita, N. A., & Budiman, A. (2017). Uji Sensitivitas Antibiotik terhadap Bakteri Penyebab Infeksi Saluran Kemih pada Pasien Rawat Inap di RSUD Prof. dr. Margono Soekarjo Purwokerto. Pharmacy, 14(2), 247–263. https://doi.org/10.30595/pharmacy.v14i2.1684

Shahbaz, K. (2017). Cephalosporins: Pharmacology and Chemistry. Pharmaceutical and Biological Evaluations, 4(6), 234–238.

LaPierre, L., Cornejo, J., Asun, A., Vergara, C., & Varela, D. (2020). Laboratory Guide: Methodologies for Antimicrobial Susceptibility Testing. APEC Secretariat.

Stafylis, C., Keith, K., Mehta, S., Tellalian, D., Burian, P., Millner, C., & Klausner, J. D. (2021). Clinical Efficacy of Cefixime for the Treatment of Early Syphilis. Clinical Infectious Diseases, 73(5), 907–910. https://doi.org/10.1093/cid/ciab187

Sarkar, P., Yarlagadda, V., Ghosh, C., & Haldar, J. (2017). A Review on Cell Wall Synthesis Inhibitors with An Emphasis on Glycopeptide Antibiotics. Medicinal Chemistry Communication, 8(3), 516–533. https://doi.org/10.1039/c6md00585c

Published

2024-11-14

How to Cite

Aktivitas Antibakteri Kokristal Sefiksim-Nikotinamida Menggunakan Agar Diffusion dan Broth Dilution Test. (2024). Jurnal Sains Dan Kesehatan, 5(6), 886-892. https://jsk.ff.unmul.ac.id/index.php/JSK/article/view/394