Investigation of Physical Properties, Solubility, Dissolution Profiles, and Flow Properties of Solid Dispersion Loading Cefixime Using Chitosan and Sodium Alginate
Article Sidebar
Keywords:
-
Cefixime, Dissolution, Flow-Properties, Formulation, Solid-Dispersion
Abstract
The co-grinding method has been used to produce solid dispersions that increase the solubility of drug substances by utilizing hydrophilic polymers. The purpose of this study was to evaluate the effect of chitosan and variations of sodium alginate as polymers on the dissolution rate of cefixime solid dispersion using the co-grinding technique. The cefixime solid dispersion formulation was made in three variations of sodium alginate formulas, namely 200 mg, 250 mg, and 300 mg. Sample characterization was carried out using XRD, FTIR, SEM, solubility testing, dissolution rate, and flow properties. The results showed that Formula 2 (F2) cefixime solid dispersion was the best formula because the degree of crystallinity decreased to 21.71%, and FTIR analysis showed the functional group interaction. Evaluation of cefixime solid dispersion showed changes in particle morphology. In addition, there was an increase in the transmittance percentage in SIF of 98.587 ± 0.019 and an increase in the dissolution rate of cefixime of 83.61%, an increase in the flow rate of 6.3 ± 0.14 grams/second, an angle of repose of 26.4 ± 0.4◦, a compressibility index of 16.3 ± 0.29%, and a Hausner ratio of 1.19 ± 0.35.
References
Ajmal, M., A. Zamir, A. Rehman, I. Imran, H. Saeed, A. Majeed, M. Aziz, F. Alqahtani, and M. F. Rasool (2023). Clinical Pharmacokinetics of Cefixime: A Systematic Review. Xenobiotica, 53(3); 149–162
Akelesh, T., S. Johnson, J. U. Chander, S. Samantha, and R. Venkatanarayanan (2015). Formulation and Evaluation of Floating Tablets of Cefixime Trihydrate Using Chitosan. Research Journal of Pharmacy and Technology, 8(11); 1502
Attia, M. S., A. A. Hasan, F. E. S. Ghazy, and E. Gomaa (2021). Solid Dispersion as a Technical Solution to Boost the Dissolution Rate and Bioavailability of Poorly Water-Soluble Drugs. Indian Journal of Pharmaceutical Education and Research, 55(2); 327–339
Basak, P. and B. Adhikari (2012). Effect of the Solubility of Antibiotics on Their Release from Degradable Polyurethane. Materials Science and Engineering C, 32(8); 2316–2322
Fini, A., J. R. Moyano, J. M. Ginés, J. I. Perez-Martinez, and A. M. R. (2005). Diclofenac Salts, II. Solid Dispersions in PEG6000 and Gelucire 50/13. European Journal of Pharmaceutics and Biopharmaceutics, 60(1); 99–111
Han, S., M. Bapoo, T. Doms, Z. Harneker, A. Louw, I. Scheepers, A. Sonday, and B. Geldenhuys (2017). FTIR, Dissolution and Anti-Viral Activity of Nevirapine Co-Crystals. Pharmaceutica Analytica Acta, 8(9); 2–10
Kalepu, S. and V. Nekkanti (2015). Insoluble Drug Delivery Strategies: Review of Recent Advances and Business Prospects. Acta Pharmaceutica Sinica B, 5(5); 442–453
Khan, F. M., M. Ahmad, and H. A. Idrees (2020). Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and In Vivo Profile. Drug Design, Development and Therapy, 14; 4303–4313
Khantri, H., M. S. Hussain, and S. Tyagi (2022). Solubility Enhancement Techniques: An Overview. World Journal of Pharmaceutical Research, 11(5); 34–40
Kim, J. and J. Ulrich (2022). Dissolution and Growth Kinetics and the Rate-Controlling Step in Transformation of Amorphous to Crystalline Phase Using Antisolvent Crystallization. Industrial and Engineering Chemistry Research, 61(39); 14609–14625
Kumari, L., Y. Choudhari, P. Patel, G. D. Gupta, D. Singh, J. M. Rosenholm, K. K. Bansal, and B. D. Kurmi (2023). Advancement in Solubilization Approaches: A Step Towards Bioavailability Enhancement of Poorly Soluble Drugs. Life, 13(5); 1099
Lali, S. P., M. Sher, M. A. Hussain, F. Hassan, M. Naeem-Ul-Hassan, M. Ahmed, and S. N. A. Bukhari (2022). Solid Dispersion Preparation of a Macrolide Drug Using Natural and Synthetic Polymers to Enhance Its Solubility and Bioavailability: A Pharmacokinetics Application. Latin American Journal of Pharmacy, 41(3); 544–555
Leuner, C. and J. Dressman (2000). Improving Drug Solubility for Oral Delivery Using Solid Dispersions. European Journal of Pharmaceutics and Biopharmaceutics, 50(1); 47–60
Lindenberg, M., S. Kopp, and J. Dressman (2014). Classification of Orally Administered Drugs on the World Health Organization Model List of Essential Medicines According to the Biopharmaceutics Classification System. European Journal of Pharmaceutics and Biopharmaceutics, 58(1); 265–278
Mardiyanto, B., Untari, A. N. Fithri, A. Mara, A. A. Aprianto, and N. G. A. (2022). The Enhancement Solubility and Stability of Erythromycin Formatted in Solid Lipid Nanoparticles by Utilizing PVA as Stabilizer. Science and Technology Indonesia, 7(2); 195–201
Mardiyanto, B., Untari, A., Mara, and N. H. Prasetyo (2023). Formulation and Evaluation of Azithromycin Dihydrate Solid Dispersion with Esther of Polyethylene Glycol-6000 and Stearic Acid Using a Co-Grinding Technique. Science and Technology Indonesia, 8(2); 312–320
O’Malley, C., P. McArdle, and A. Erxleben (2021). Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation. In Proceedings, volume 78. MDPI, pages 2–10
Rekdal, M., A. Pai, R. Choudhari, and M. B. Sathyanarayana (2018). Applications of Co-Crystals in Pharmaceutical Drugs. Systematic Reviews in Pharmacy, 9(1); 55
Shankar, P. R., R. M. Piryani, and S. Piryani (2017). The State of the World’s Antibiotics 2015. Journal of Chitwan Medical College, 6(4); 68–69
Silver, L. L. and K. A. Bostian (1993). Discovery and Development of New Antibiotics: The Problem of Antibiotic Resistance. Antimicrobial Agents and Chemotherapy, 37(3); 377–383
Simeis, D. D. and S. Serra (2021). Actinomycetes: A Never-Ending Source of Bioactive Compounds—An Overview on Antibiotics Production. Antibiotics, 10(5); 483
Spellberg, B. (2014). The Future of Antibiotics. Critical Care, 18(3); 1–7
Tajmir, F. and A. Roosta (2020). Solubility of Cefixime in Aqueous Mixtures of Deep Eutectic Solvents from Experimental Study and Modeling. Journal of Molecular Liquids, 303; 112636
Urakov, A. L., N. A. Urakova, and A. P. Reshetnikov (2021). Physical–Chemical Properties of Antibiotic Drugs: What We Miss in Our Research. Japanese Dental Science Review, 57; 158
Wu, X., Y. Wang, J. Xue, J. Liu, J. Qin, Z. Hong, and Y. Du (2020). Solid Phase Drug-Drug Pharmaceutical Co-Crystal Formed Between Pyrazinamide and Diflunisal: Structural Characterization. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 234; 118265
Akelesh, T., S. Johnson, J. U. Chander, S. Samantha, and R. Venkatanarayanan (2015). Formulation and Evaluation of Floating Tablets of Cefixime Trihydrate Using Chitosan. Research Journal of Pharmacy and Technology, 8(11); 1502
Attia, M. S., A. A. Hasan, F. E. S. Ghazy, and E. Gomaa (2021). Solid Dispersion as a Technical Solution to Boost the Dissolution Rate and Bioavailability of Poorly Water-Soluble Drugs. Indian Journal of Pharmaceutical Education and Research, 55(2); 327–339
Basak, P. and B. Adhikari (2012). Effect of the Solubility of Antibiotics on Their Release from Degradable Polyurethane. Materials Science and Engineering C, 32(8); 2316–2322
Fini, A., J. R. Moyano, J. M. Ginés, J. I. Perez-Martinez, and A. M. R. (2005). Diclofenac Salts, II. Solid Dispersions in PEG6000 and Gelucire 50/13. European Journal of Pharmaceutics and Biopharmaceutics, 60(1); 99–111
Han, S., M. Bapoo, T. Doms, Z. Harneker, A. Louw, I. Scheepers, A. Sonday, and B. Geldenhuys (2017). FTIR, Dissolution and Anti-Viral Activity of Nevirapine Co-Crystals. Pharmaceutica Analytica Acta, 8(9); 2–10
Kalepu, S. and V. Nekkanti (2015). Insoluble Drug Delivery Strategies: Review of Recent Advances and Business Prospects. Acta Pharmaceutica Sinica B, 5(5); 442–453
Khan, F. M., M. Ahmad, and H. A. Idrees (2020). Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and In Vivo Profile. Drug Design, Development and Therapy, 14; 4303–4313
Khantri, H., M. S. Hussain, and S. Tyagi (2022). Solubility Enhancement Techniques: An Overview. World Journal of Pharmaceutical Research, 11(5); 34–40
Kim, J. and J. Ulrich (2022). Dissolution and Growth Kinetics and the Rate-Controlling Step in Transformation of Amorphous to Crystalline Phase Using Antisolvent Crystallization. Industrial and Engineering Chemistry Research, 61(39); 14609–14625
Kumari, L., Y. Choudhari, P. Patel, G. D. Gupta, D. Singh, J. M. Rosenholm, K. K. Bansal, and B. D. Kurmi (2023). Advancement in Solubilization Approaches: A Step Towards Bioavailability Enhancement of Poorly Soluble Drugs. Life, 13(5); 1099
Lali, S. P., M. Sher, M. A. Hussain, F. Hassan, M. Naeem-Ul-Hassan, M. Ahmed, and S. N. A. Bukhari (2022). Solid Dispersion Preparation of a Macrolide Drug Using Natural and Synthetic Polymers to Enhance Its Solubility and Bioavailability: A Pharmacokinetics Application. Latin American Journal of Pharmacy, 41(3); 544–555
Leuner, C. and J. Dressman (2000). Improving Drug Solubility for Oral Delivery Using Solid Dispersions. European Journal of Pharmaceutics and Biopharmaceutics, 50(1); 47–60
Lindenberg, M., S. Kopp, and J. Dressman (2014). Classification of Orally Administered Drugs on the World Health Organization Model List of Essential Medicines According to the Biopharmaceutics Classification System. European Journal of Pharmaceutics and Biopharmaceutics, 58(1); 265–278
Mardiyanto, B., Untari, A. N. Fithri, A. Mara, A. A. Aprianto, and N. G. A. (2022). The Enhancement Solubility and Stability of Erythromycin Formatted in Solid Lipid Nanoparticles by Utilizing PVA as Stabilizer. Science and Technology Indonesia, 7(2); 195–201
Mardiyanto, B., Untari, A., Mara, and N. H. Prasetyo (2023). Formulation and Evaluation of Azithromycin Dihydrate Solid Dispersion with Esther of Polyethylene Glycol-6000 and Stearic Acid Using a Co-Grinding Technique. Science and Technology Indonesia, 8(2); 312–320
O’Malley, C., P. McArdle, and A. Erxleben (2021). Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation. In Proceedings, volume 78. MDPI, pages 2–10
Rekdal, M., A. Pai, R. Choudhari, and M. B. Sathyanarayana (2018). Applications of Co-Crystals in Pharmaceutical Drugs. Systematic Reviews in Pharmacy, 9(1); 55
Shankar, P. R., R. M. Piryani, and S. Piryani (2017). The State of the World’s Antibiotics 2015. Journal of Chitwan Medical College, 6(4); 68–69
Silver, L. L. and K. A. Bostian (1993). Discovery and Development of New Antibiotics: The Problem of Antibiotic Resistance. Antimicrobial Agents and Chemotherapy, 37(3); 377–383
Simeis, D. D. and S. Serra (2021). Actinomycetes: A Never-Ending Source of Bioactive Compounds—An Overview on Antibiotics Production. Antibiotics, 10(5); 483
Spellberg, B. (2014). The Future of Antibiotics. Critical Care, 18(3); 1–7
Tajmir, F. and A. Roosta (2020). Solubility of Cefixime in Aqueous Mixtures of Deep Eutectic Solvents from Experimental Study and Modeling. Journal of Molecular Liquids, 303; 112636
Urakov, A. L., N. A. Urakova, and A. P. Reshetnikov (2021). Physical–Chemical Properties of Antibiotic Drugs: What We Miss in Our Research. Japanese Dental Science Review, 57; 158
Wu, X., Y. Wang, J. Xue, J. Liu, J. Qin, Z. Hong, and Y. Du (2020). Solid Phase Drug-Drug Pharmaceutical Co-Crystal Formed Between Pyrazinamide and Diflunisal: Structural Characterization. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 234; 118265
Authors
Mardiyanto, Fithri, N. A. ., Shiyan, S. ., & Satrio, F. D. . (2025). Investigation of Physical Properties, Solubility, Dissolution Profiles, and Flow Properties of Solid Dispersion Loading Cefixime Using Chitosan and Sodium Alginate. Science and Technology Indonesia, 10(3), 943–951. https://doi.org/10.26554/sti.2025.10.3.943-951
This work is licensed under a Creative Commons Attribution 4.0 International License.