Effect of CaCl2 Crosslinker Concentration On The Characteristics, Release and Stability of Ciprofloxacin HCl-Alginate-Carrageenan Microspheres
Downloads
Background: Ciprofloxacin HCl is a broad-spectrum fluoroquinolone antibiotic that has the lowest MIC against Mycobacterium tuberculosis but has limitations in oral use, so inhalation microspheres are made. Objective: This study aimed to investigate the effect of CaCl2 crosslinker concentration on the characteristics, release and stability of ciprofloxacin-alginate-carrageenan microspheres. Methods: Microspheres were prepared by ionotropic gelation using aerosolization with calcium chloride 0.5M (F1), 1.0M (F2), 1.5M (F3), 2.0M (F4) as crosslinker and then dried using freeze dryer. Results: Ciprofloxacin-alginate-carrageenan microspheres formed of yellowish-white powder, smooth morphology and excellent flow properties with the particle size of less than 5µm, drug loading and entrapment efficiency were between 2.05% - 2.42% and 75.34% - 98.09%, yield was between 84.69% - 97.57%, moisture content of less than 10%. Ciprofloxacin-alginate-carrageenan microspheres with 1.5M crosslinker (F3) was the optimal formula. For 12 hours, ciprofloxacin released was 49.89% - 63.78% at pH 7.4, and the kinetics of drug release showed that of Korsmeyer-peppas with a mechanism based on fickian diffusion. The microspheres were discovered to be stable for up to 28 days of storage. Conclusion: The increased concentration of the CaCl2 crosslinker from 0.5M to 2.0M decreased the particle size and drug release but increased the yield, drug loading and entrapment efficiency.
Abdelghany, S., Alkhawaldeh, M. & Alkhatib, H. S. (2017). Carrageenan-Stabilized Chitosan Alginate Nanoparticles Loaded with Ethionamide for the Treatment of Tuberculosis. Journal of Drug Delivery Science and Technology; 39; 442–449. doi: 10.1016/j.jddst.2017.04.034.
Adrian, G., Mihai, M. & Vodnar, D. C. (2019). The Use of Chitosan, Alginate, and Pectin in the Biomedical and Food Sector-Biocompatibility, Bioadhesiveness, and Biodegradability. Polymers; 11; 7–11.
Ashish, K., Hiralal, A. C. & Prajkta, U. (2012). Pulmonary Drug Delivery System. International Journal of PharmTech Research; 4; 293–305.
Balagani, P. K., Chandiran, I., Bhavya, B. & Manubolu, S. (2011). Microparticulate Drug Delivery System: A Review. Indian Journal of Pharmaceutical Science & Research; 1; 19-37.
Bayer Health Care Pharmaceuticals Inc. (2021). Ciprofloxacin Hydrochloride (Tablets and Oral Suspension) Draft; 26-30. Whippany: Bayer Health Care Pharmaceuticals Inc.
Berger, J. R., Mayer, M., Felt, J. M., Peppas, O. N A. & Gurny, R. (2004). Structure and Interactions in Covalently and Ionically Crosslinked Chitosan Hydrogels for Biomedical Applications. European Journal of Pharmaceutics and Biopharmaceutics; 57; 19–34. doi: 10.1016/S0939-6411(03)00161-9.
Bruschi, M. L. B T. (2015). Mathematical Models of Drug Release. In Strategies to Modify the Drug Release from Pharmaceutical Systems; 63-86. Sawston: Woodhead Publishing.
Dhakar, R. C., Maurya, S. D., Sagar, B., Bhagat, S., Kumar, S. & Jain, C. (2010). Variables Influencing the Drug Entrapment Efficiency of Microspheres: A Pharmaceutical Review. Der Pharmacia Lettre; 2; 102-116.
Freiberg, S., & Zhu, X. X. (2004). Review Polymer Microspheres for Controlled Drug Release. International Journal of Pharmaceutics; 282; 1–18. doi: 10.1016/j.ijpharm.2004.04.013.
Gaber, D. M. & Nafee, N. & Abdallah, O. Y. (2021). Inhalable Nano-Embedded Microspheres as an Emerging Way for Local Treatment of Lung Carcinoma: Benefits, Methods of Preparation & Characterizaton. Advances in Medical, Pharmaceutical and Dental Research Journal; 1; 7–16. doi: 10.21622/AMPDR.2021.01.1.007.
Gedam, S., Jadhav, P., Talele, S. & Jadhav, A. (2018). Effect of Crosslinking Agent on Development of Gastroretentive Mucoadhesive Microspheres of Risedronate Sodium. International Journal of Applied Pharmaceutics; 10; 133–40. doi: 10.22159/ijap.2018v10i4.26071.
Hariyadi, D. M., Hendradi, E., Rahmadi, M., Bontong, E. S. & Islam, N. (2022). In-Vitro Physicochemical Properties And Antibacterial Activity Of Ciprofloxacin Carrageenan Inhalable Microspheres. Rasayan Journal of Chemistry; 15; 132–142. doi: 10.31788/RJC.2022.1516652.
Hariyadi, D. M., Hendradi, E. & Sharon, N. (2019). Development of Carrageenan Polymer for Encapsulation of Ciprofloxacin HCL: In Vitro Characterization. International Journal of Drug Delivery Technology; 9; 89–93. doi: 10.25258/ijddt.9.1.14.
Hariyadi, D. M., Purwanti, T. & Adilla, S. (2018). Influence of Crosslinker Concentration on the Characteristics of Erythropoietin-Alginate Microspheres. Journal of Pharmacy & Pharmacognosy Research; 6; 250–259.
Hariyadi, D. M., Hendradi, E., Purwanti, T., Permana, F. F. D. G. & Ramadani, C. N. (2014). Effect of Cross Linking Agent and Polymer on the Characteristics of Ovalbumin Loaded Alginate Microspheres. International Journal of Pharmacy and Pharmaceutical Sciences; 6; 469–474.
Hariyadi, D. M., Hendradi, E. & Kurniawan, T. D. (2019). Alginate Microspheres Encapsulating Ciprofloxacin HCl: Characteristics, Release and Antibacterial Activity. International Journal of Pharma Research and Health Sciences; 7; 3020–3027. doi: 10.21276/ijprhs.2019.04.02.
Hariyadi, D. M., Purwanti, T. & Wardani, D. (2016). Stability of Freeze-Dried Ovalbumin-Alginate Microspheres with Different Lyoprotectants. Research Journal of Pharmacy and Technology; 9; 20–26. doi: 10.5958/0974-360X.2016.00005.6.
Hariyadi, D. M. & Hendradi, E. (2020). Optimization Performance and Physical Stability of Ciprofloxacin HCL- Ca Alginate Microspheres : Effect of Different Concentration of Alginate. International Journal of Drug Delivery Technology; 89–94. doi: 10.25258/ijddt.10.1.15.
Heifetst, L. B. & Lindholm-levy, P. J. (1987). Bacteriostatic and Bactericidal Activity of Ciprofloxacln and Ofloxacin Against Mycobacterium Tuberculosis and Mycobacterlum Avium Complex. National Jewish Center for Immunology and Respiratory Medicine; 68; 267-276.
Jerome, A., Onda, M. & Aquino, J. A. (2020). Evaluation of Factors Affecting the Microencapsulation of Mefenamic Acid with Cellulose Acetate Phthalate. Pharmaceutical Sciences Asia; 47; 130–141. doi: 10.29090/psa.2020.02.018.0055.
Kadam, N. R. & Suvarna. (2015). Microsphere: A Brief Review. Asian Journal of Biomedical and Pharmaceutical Sciences; 5; 13–19. doi: 10.15272/ajbps.v5i47.713.
Kalalo, T., Miatmoko, A., Tanojo, H., Erawati, T., Hariyadi, D. M. & Rosita, N. (2022). Effect of Sodium Alginate Concentration on Characteristics, Stability and Drug Release of Inhalation Quercetin Microspheres. Jurnal Farmasi Dan Ilmu Kefarmasian Indonesia; 9; 107–114. doi: 10.20473/jfiki.v9i22022.107-114.
Karimi, K., Pallagi, E., Szabó-révész, P., Csóka, I. & Ambrus, R. (2016). Development of a Microparticle-Based Dry Powder Inhalation Formulation of Ciprofloxacin Hydrochloride Applying the Quality by Design Approach. Drug Design, Development and Therapy; 10; 3331–3343. doi: 10.2147/DDDT.S116443.
Katzung, B. G., Masters, S. B. & Trevor, A. J. (2012). Basic & Clinical Pharmacology Twelfth Edition; 834-838. New York: McGraw-Hill Education.
Kolesnyk, I. S. & Burban, A. (2015). Alginate / κ -Carrageenan Microspheres and Their Application for Protein Drugs Controlled Release. Chemistry and Chemical Technology; 9; 485–492. doi: 10.23939/chcht09.04.485.
Lane, J. (2016). Powder Flow. North Bethesda: United States Pharmacopeia.
Laura, T Furlan Rodríguez, Antonio Pérez Padilla, and Mercedes E Campderrós. (2010). Inulin like Lyoprotectant of Bovine Plasma Proteins Concentrated by Ultrafiltration. Food Research International; 43; 788–796. doi: 10.1016/j.foodres.2009.11.015.
Lee, Kuen Yong, and David J. Mooney. (2012). Alginate: Properties and Biomedical Applications. Progress in Polymer Science (Oxford); 37; 106–126. doi: 10.1016/j.progpolymsci.2011.06.003.
Lengyel, Miléna, Nikolett Kállai-Szabó, Vince Antal, András József Laki and István Antal. (2019). Microparticles, Microspheres, and Microcapsules for Advanced Drug Delivery. Scientia Pharmaceutica; 87; 1-31. doi: 10.3390/scipharm87030020.
Li, L., Wang, Q., Li, H., Yuan, M. & Yuan, M. (2014). Preparation, Characterization, In Vitro Release and Degradation of Cathelicidin-BF-30-PLGA Microspheres. PLoS ONE; 9; 1–7. doi: 10.1371/journal.pone.0100809.
Lin, X., Yang, H., Su, L., Yang, Z. & Tang, X. (2018). Effect of Size on the in Vitro/in Vivo Drug Release and Degradation of Exenatide-Loaded PLGA Microspheres. Journal of Drug Delivery Science and Technology; 45; 346-356 doi: 10.1016/j.jddst.2018.03.024.
Manjanna, K. M., Pramod, T. M. & Shivakumar, B. (2010). Calcium Alginate Cross-Linked Polymeric Microbeads for Oral Sustained Drug Delivery in Arthritis. Drug Discoveries & Therapeutics; 4; 109–122.
Misra, A., Hickey, A. J., Rossi, C., Borchard, G., Terada, H., Makino, K., Fourie, P. B. & Colombo, P. (2011). Inhaled Drug Therapy for Treatment of Tuberculosis. Tuberculosis; 91; 71–81. doi: 10.1016/j.tube.2010.08.009.
Pasquale, S. S., Pedroso-Santana, Y., Nicolas, K., Patrick, J. & Bocchetta, M. P. (2021). Ionotropic Gerlation of Chitosan Flat Structures and Potential Applications. Molecules; 26; 1–28.
Ra, A. C., Chun, Y. G., Kim, B. K. & Park, D. J. (2014). Preparation of Alginate – CaCl 2 Microspheres as Resveratrol Carriers. Journal of Materials Science; 49; 4612–4619. doi: 10.1007/s10853-014-8163-x.
Saha, T., Sinha, S., Harfoot, R. & Quiñones-mateu, M. E. (2022). Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder. Pharmaceutics; 14; 1–20.
Santa-maria, M., Scher, H. & Jeoh, T. (2012). Microencapsulation of Bioactives in Cross-Linked Alginate Matrices by Spray Drying. Journal ofMicroencapsulation; 29; 286–195. doi: 10.3109/02652048.2011.651494.
Rajeswari, S., Prasanthi, T., Sudha, N., Swain, R. P.. Satyajit Panda and Vinusha Goka. (2017). Natural Polymers : A Recent Review. World Journal of Pharmacy and Pharmaceutical Sciences; 6; 472–494. doi: 10.20959/wjpps20178-9762.
Shan, L., Tao, E. X., Meng, Q. H., Hou, W. X., Liu, K., Shang, H. C., Tang, J. B. & Zhang, W. F. (2016). Formulation, Optimization, and Pharmacodynamic Evaluation of Chitosan/Phospholipid/β-Cyclodextrin Microspheres. Drug Design, Development and Therapy; 10; 417–429. doi: 10.2147/DDDT.S97982.
Tecante, A. & Núñez, C. (2012). Solution Properties of κ -Carrageenan and Its Interaction with Other Polysaccharides in Aqueous Media. Rheology In Tech; 241–264.
Thai, T., Salisbury, B. H. & Zito, P. M. (2022). Ciprofloxacin. London: Treasure Island (FL).
Varela-Fernández, R. (2022). Design, Optimization, and in Vitro Characterization of Idebenone-Loaded PLGA Microspheres for LHON Treatment. International Journal of Pharmaceutics; 616; 1-19. doi: /10.1016/j.ijpharm.2022.121504.
Wathoniyyah, M. (2016). Pembuatan Dan Karakterisasi Komposit Sodium Alginat-Karaginan Dengan Crosslinker CaCl2 Dan Plasticizer Gliserol Sebagai Material Drug Release. Skripsi; Fakultas Sains dan Teknologi Universitas Airlangga, Surabaya.
Wijaksana, A. (2022). Pengaruh Konsentrasi Kombinasi Polimer Alginat-Karagenan Terhadap Pelepasan Dan Aktivitas Antibakteri Dari Pulmosfer Ciprofloxacin HCl. Skripsi; Fakultas Farmasi Universitas Airlangga, Surabaya.
Yu, F., Cui, T., Yang, C., Dai, X. & Ma, J. (2019). K -Carrageenan / Sodium Alginate Double-Network Hydrogel with Enhanced Mechanical Properties, Anti-Swelling, and Adsorption Capacity.Chemosphere; 237; 1-7. doi: 10.1016/j.chemosphere.2019.124417.
Copyright (c) 2023 JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
1. The copyright of this journal belongs to the Editorial Board and Journal Manager with the author's knowledge, while the moral right of the publication belong to the author.
2. The formal legal aspect of journal publication accessibility refers to the Creative Commons Attribution-Non-Commercial-Share Alike (CC BY-NC-SA), which implies that the publication can be used for non-commercial purposes in its original form.
3. Every publication (print/electronic) is open access for educational, research, and library purposes. In addition to the objectives mentioned above, the editorial board is not responsible for copyright infringement
.jpg)
