Cocrystals of Cefixime with Nicotinamide: Improved Solubility, Dissolution, and Permeability

  • Abulkhair Abdullah Universitas Khairun
  • Mutmainnah Mutmainnah Universitas Khairun
  • Erindyah R. Wikantyasning Universitas Muhammadiyah Surakarta
Keywords: cocrystal, characterization, solubility, dissolution, permeability


Cefixime is a third-generation cephalosporin antibiotic with poor solubility and permeability. The aim was to compared between Dry Grinding (DG) and Liquid-Assisted Grinding (LAG) methods to formed cocrystal of cefixime with nicotinamide. Cocrystal was prepared in 1:1 molar ratio and was characterizated by differential scanning calorimetry (DSC), fourier transform infra-red (FTIR), scanning electron microscopy (SEM), x-ray diffraction (XRD) methods. Cocrystal properties such as solubility, dissolution rate, and permeation rate were evaluated. The solubility test results obtained: 0.420 ± 0.016 (cefixime); 0.675 ± 0.016 (cocrystal 1:1 LAG); and 0.632 ± 0.016 (cocrystal 1:1 DG). The dissolution test results obtained: 186.55 ± 4.18 (cefixime); 232.83 ± 4.07 (cocrystal 1:1 LAG); and 228.82 ± 10.07 (cocrystal 1:1 DG). The permeability test results obtained: 153.58 ± 31.94 (cefixime); 306.22 ± 77.81 (cocrystal 1:1 LAG); and 211.44 ± 22.90 (cocrystal 1:1 DG). Cefixime can be formed into cocrystal with nicotinamide by DG and LAG methods according to the results of characterization using DSC, FTIR, SEM, and XRD accompanied by the increasing solubility, dissolution, and permeability. Cocrystal 1:1 LAG showed better result compared to cocrystal 1:1 DG.


Arora, S. C., Sharma, P. K., Irchhaiya, R., Khatkar, A., Singh, N., & Gagoria, J. (2010). Development, Characterization, and Solubility Study of Solid Dispersion of Cefixie Trihydrate by Solvent Evaporation Method. International Journal of Drug Development and Research, 2(2), 230–424.
Fabian, L., Hamill, N., Eccles, K. S., Moynihan, H. A., Maguire, A. R., McCausland, L., & Lawrence, S. E. (2011). Cocrystals of Fenamic Acids with Nicotinamide. Crystal Growth and Design, 11, 3522–3528.
Izutsu, K., Koide, T., Takata, N., Ikeda, Y., Ono, M., Inoue, M., Fukami, T., & Yonemochi, E. (2016). Characterization and Quality Control of Pharmaceutical Cocrystals. Chemical and Pharmaceutical Bulletin, 64(10), 1421–1430.
Karagianni, A., Malamatari, M., & Kachrimanis, K. (2018). Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs. Pharmaceutics, 10(18), 1–30.
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.
Lu, J., & Rohani, S. (2009). Preparation and Characterization of Theophylline-Nicotinamide Cocrystal. Organic Process Research & Development, 13, 1269–1275.
Mbah, C., Uzor, P., & Omeje, E. (2011). Perspectives on Transdermal Drug Delivery. Journal of Chemical and Pharmaceutical Research, 3(3), 680–700.
Qiao, N., Li, M., Schlindwein, W., Malek, N., Davies, A., & Trappitt, G. (2011). Pharmaceutical Cocrystals: An Overview. International Journal of Pharmaceutics, 419, 1–11.
Savjani, K. T., Gajjar, A. K., & Savjani, J. K. (2012). Drug Solubility: Importance and Enhancement Techniques. ISRN Pharmaceutics.
Schultheiss, N., & Newman, A. (2009). Pharmaceutical Cocrystals and Their Physicochemical Properties. Crystal Growth and Design, 9(6), 2950–2967.
Sevukarajan, M., Thanuja, B., Sodanapalli, R., & Nair, R. (2011). Synthesis and Characterization of a Pharmaceutical Co-Crystal: (Aceclofenac:Nicotinamide ). Journal of Pharmaceutical Sciences and Research, 3(6), 1288–1293.
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.
Sweetman, S. C. (2009). Martindale: The Complete Drug Reference (36th ed.). Pharmaceutical Press.
Wishart, D. S., Knox, C., Guo, A. C., Shrivastava, S., Hassanali, M., Stothard, P., Chang, Z., Woolsey, J., & Tg, C. (2006). DrugBank: A Comprehensive Resource for In Silico Drug Discovery and Exploration. 34, 668–672.
How to Cite
Abdullah, A., Mutmainnah, M., & Wikantyasning, E. R. (2022). Cocrystals of Cefixime with Nicotinamide: Improved Solubility, Dissolution, and Permeability. Indonesian Journal of Pharmacy, 33(3), 394-400.
Research Article