Characteristics, Release, and Stability (Kinetics and Shelf-life) of Ciprofloxacin HCl-Alginate-Carrageenan Microspheres: Effects of Drug Concentration and Type of Lyoprotectant
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Keywords:
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Ciprofloxacin HCl, Alginate-Carrageenan Microspheres, Drug Concentration, Lyoprotectant, Release, Stability
Abstract
Tuberculosis, an infectious disease caused by the Mycobacterium tuberculosis bacteria, is one of the main causes of death worldwide. Alternative treatments are necessary due to the rising prevalence of medication resistance in Mycobacterium tuberculosis. Fluoroquinolones, such as ciprofloxacin HCl, are among these alternatives and are generally administered orally, but they have limitations. Therefore, pulmonary targeted inhalation delivery systems have been developed. Inhalation of microspheres enables deposition in the lungs at appropriate particle sizes. This study formulates ciprofloxacin HCl microspheres with an optimal ratio and concentration of polymer combination and crosslinker, aiming to determine the effect of drug concentration and lyoprotectant type on characteristics, release, and stability, including degradation kinetics and shelf life. The results showed that the ciprofloxacin HCl-alginate-carrageenan microsphere powder was yellowish-white, with smooth morphology, a yield percentage of 96.08% ± 0.84 – 97.00% ± 0.19, particle sizes below 5 µm, drug loading between 4.57% ± 0.13 – 6.76% ± 0.06, and entrapment efficiency ranging from 79.45% ± 2.53 – 90.80% ± 0.77. The powder had moisture content below 5% and excellent flow properties. Ciprofloxacin HCl release from microspheres at pH 7.4 for 30 hours was 84.55% ± 0.89 – 90.74% ± 0.22, following Korsmeyer-Peppas kinetics based on the Fickian diffusion mechanism. Ciprofloxacin HCl-alginate-carrageenan microspheres were stable and exhibited good shelf life. This study concluded that particle size, drug loading, entrapment efficiency, and drug release are all influenced by drug concentration, while moisture content and flow properties, with adequate shelf life, are influenced by the type of lyoprotectant.
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Chotchindakun, K., J. Pekkoh, J. Ruangsuriya, K. Zheng, I. Unalan, and A. R. Boccaccini (2021). Fabrication and Characterization of Cinnamaldehyde-Loaded Mesoporous Bioactive Glass Nanoparticles/PHBV-Based Microspheres for Preventing Bacterial Infection and Promoting Bone Tissue Regeneration. Polymers, 13(11); 1794
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Fitriani, L., Z. Arif, U. Hasanah, and E. Zaini (2025). Enhancing the Solubility and Dissolution Rate of Tenoxicam through Co-Amorphous Formation with Meglumine by a Solvent Dropped Grinding Method. Science and Technology Indonesia, 10(1); 131–138
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Hariyadi, D. M., T. Erawati, N. Rosita, G. Desanto, and A. Trinanda (2023). Influence of Polymer Combination Concentration on the Characteristics, In Vitro Release, and In Vivo Lung Deposition of Alginate-Carrageenan Microspheres Encapsulating Ciprofloxacin HCl. Indonesian Journal of Pharmacy, 34(1); 162–173
Hariyadi, D. M., E. Hendradi, and T. D. Kurniawan (2019). Alginate Microspheres Encapsulating Ciprofloxacin HCl: Characteristics, Release and Antibacterial Activity. International Journal of Pharma Research and Health Sciences, 7(4); 3020–3027
Hariyadi, D. M., E. Hendradi, M. Rahmadi, N. Bontong, E. Pudjadi, and N. Islam (2022). In-vitro Physicochemical Properties and Antibacterial Activity of Ciprofloxacin-Carragenan Inhalable Microspheres. Rasayan Journal of Chemistry, 15(1); 132–142
Hariyadi, D. M., T. Purwanti, and S. Adilla (2018). Influence of Crosslinker Concentration on the Characteristics of Erythropoietin-Alginate Microspheres. Journal of Pharmacy and Pharmacognosy Research, 6(4); 250–259
Hariyadi, D. M., T. Purwanti, and D. Wardani (2016). Stability of Freeze-Dried Ovalbumin-Alginate Microspheres with Different Lyoprotectants. Research Journal of Pharmacy and Technology, 9(1); 20–26
Heifets, L. B. and P. J. Lindholm-Levy (1987). Bacteriostatic and Bactericidal Activity of Ciprofloxacin and Ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium Complex. Tubercle, 68(4); 267–276
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Huang, R., H. Zhang, L. Lv, Y. Zhang, J. Li, H. Wang, and W. Gao (2023). Design of Gefitinib-Loaded PLGA Microspheres Via Microfluidics for Lung Cancer. Materials and Design, 234; 112336
Jelvehgari, M., A. Nokhodchi, M. Rezapour, and H. Valizadeh (2010). Effect of Formulation and Processing Variables on the Characteristics of Tolmetin Microspheres Prepared by Double Emulsion Solvent Diffusion Method. Indian Journal of Pharmaceutical Sciences, 72(1); 72–78
Jerome, A., M. Onda, and J. A. Aquino (2020). Evaluation of Factors Affecting the Microencapsulation of Mefenamic Acid with Cellulose Acetate Phthalate. Pharmaceutical Sciences Asia, 47(2); 130–141
Kalalo, T., A. Miatmoko, H. Tanojo, T. Erawati, D. M. Hariyadi, and N. Rosita (2022). Effect of Sodium Alginate Concentration on Characteristics, Stability and Drug Release of Inhalation Quercetin Microspheres. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia, 9(2); 107–114
Kalman, H. (2021). Effect of Moisture Content on Flowability: Angle of Repose, Tilting Angle, and Hausner Ratio. Powder Technology, 393; 582–596
Karhale, A. A., H. S. Chaudhari, P. L. Ughade, D. T. Baviskar, and D. K. Jain (2012). Pulmonary Drug Delivery System. International Journal of PharmTech Research, 4(1); 293–305
Karunnanithy, V., N. H. B. Abdul Rahman, N. A. H. Abdullah, M. B. Fauzi, Y. Lokanathan, A. N. MinHwei, and M. Maarof (2024). Effectiveness of Lyoprotectants in Protein Stabilization During Lyophilization. Pharmaceutics, 16(10); 1–16
Kolesnyk, I. S. and A. Burban (2015). Alginate / κ-Carrageenan Microspheres and their Application for Protein Drugs Controlled Release. Chemistry and Chemical Technology, 9(4); 485–492
Kurniawan, M. F., D. Setyawan, and D. M. Hariyadi (2024). Quercetin in Drug Carriers: Polymer Composite, Physical Characteristics, and in Vitro Study. Science and Technology Indonesia, 9(2); 380–412
Lane, J. (2016). Powder Flow. United States Pharmacopeia, 30(6); 1–7
Lee, K. Y. and D. J. Mooney (2012). Alginate: Properties and Biomedical Applications. Progress in Polymer Science, 37(1); 106–126
Lengyel, M., N. Kállai-Szabó, V. Antal, A. J. Laki, and I. Antal (2019). Microparticles, Microspheres, and Microcapsules for Advanced Drug Delivery. Scientia Pharmaceutica, 87(3); 20
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Liempepas, A., M. Rahmadi, F. Ifadotunnikmah, and D. M. Hariyadi (2025). Effect of Sodium Alginate-Carrageenan Concentration in Rifampicin Pulmospheres on Physical Characteristics, Release, and Anti-Tuberculosis Activity. Science and Technology Indonesia, 10(3); 817–825
Mehta, P., C. Bothiraja, S. Kadam, and A. Pawar (2018). Potential of Dry Powder Inhalers for Tuberculosis Therapy: Facts, Fidelity and Future. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup3); S791–S806
Parameswari, C. S., B. Manasa, K. Mounika, N. N. Sree, and M. Rajeswari (2024). Microspheres. International Journal of Pharmaceutical Sciences, 2(12); 502–519
Rowe, R. C., P. J. Sheskey, and S. C. Owen (2009). Handbook of Pharmaceutical Excipients. Pharmaceutical Press, London, 6th edition
Sacco, P., S. Pedroso-Santana, Y. Kumar, N. Joly, P. Martin, and P. Bizzaro (2021). Ionotropic Gelation of Chitosan Flat Structures and Potential Applications. Molecules, 26; 660
Saha, T., S. Sinha, R. Harfoot, and M. E. Quiñones-Mateu (2022). Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder. Pharmaceutics, 14(1420); 1–20
Scrivens, G., D. Clancy, and P. Gerst (2018). Theory and Fundamentals of Accelerated Predictive Stability (APS) Studies. In Accelerated Predictive Stability (APS): Fundamentals and Pharmaceutical Industry Practices. Elsevier Inc., pages 21–52
Shan, L., E. X. Tao, Q. H. Meng, W. X. Hou, K. Liu, H. C. Shang, J. B. Tang, and W. Zhang (2016). Formulation, Optimization, and Pharmacodynamic Evaluation of Chitosan/Phospholipid/β-Cyclodextrin Microspheres. Drug Design, Development and Therapy, 10; 417–429
Thai, T., B. Salisbury, and P. Zito (2022). Ciprofloxacin. StatPearls; 2022
Varela-Fernández, R., C. Bendicho-Lavilla, M. Martin-Pastor, R. H. Vanrell, M. I. Lema-Gesto, M. González-Barcia, and F. J. Otero-Espinar (2022). Design, Optimization, and in Vitro Characterization of Idebenone-Loaded PLGA Microspheres for LHON Treatment. International Journal of Pharmaceutics, 616; 121504
Verma, R., S. Verma, and K. Sokindra (2019). Microsphere-A Novel Drug Delivery System. Research Chronicle in Health Sciences, 5(1); 5–14
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Authors
Amiruddin, Rahmadi, M., & Hariyadi, D. M. (2026). Characteristics, Release, and Stability (Kinetics and Shelf-life) of Ciprofloxacin HCl-Alginate-Carrageenan Microspheres: Effects of Drug Concentration and Type of Lyoprotectant. Science and Technology Indonesia, 11(1), 148–160. https://doi.org/10.26554/sti.2026.11.1.148-160
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