Effect of Sodium Alginate-Carrageenan Concentration in Rifampicin Pulmospheres on Physical Characteristics, Release, and Anti-Tuberculosis Activity
Article Sidebar
Keywords:
-
Pulmospheres, Rifampicin, Sodium Alginate-Carrageenan, Anti-Tuberculosis, Mycobacterium smegmatis
Abstract
Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which mostly attacks the lungs, but can also affect other organs. Tuberculosis is one of the biggest health problems worldwide. Conventional oral rifampicin preparations have several limitations, such as poor bioavailability, low solubility, and drug instability in the gastrointestinal fluid. Only a small portion of the tuberculosis drug can reach the alveoli, the main target of the tuberculosis drug. Drug delivery Systems are one of the solutions to this problem. They are a formulation or system that can mediate the delivery of therapeutic substances in the body to increase therapeutic effects, reduce drug side effects, increase bioavailability, and improve patient compliance. Pulmonary drug delivery requires a small dose and particle size, so microspheres are selected for lung delivery. This research aims to study the effect of sodium alginate concentration and carrageenan (0.75%, 1%, 1.25%) with a ratio of 1:1 on physical characteristics, in vitro release, and anti-tuberculosis activity. Preparation of Rifampicin Sodium Alginate-Carageenan Pulmospheres with Ionotropic Gelation-Aerosolization. Pulmospheres were evaluated for entrapment efficiency, morphology, yield, particle size, drug loading, in vitro release, and Mycobacterium smegmatis activity. Increasing concentrations of sodium alginate and carrageenan produce rifampicin pulmospheres with good physical characteristics, increase rifampicin release, and result in inhibitory activity against Mycobacterium smegmatis
References
Alavi, S. and S. A. Mortazavi (2018). Freeze-Dried K–Carrageenan/Chitosan Polyelectrolyte Complex-Based Insert: A Novel Intranasal Delivery System for Sumatriptan Succinate. Iranian Journal of Pharmaceutical Research, 17(4); 1172–1181
Alipour, S., H. Montaseri, and M. Tafaghodi (2010). Preparation and Characterization of Biodegradable Paclitaxel-Loaded Alginate Microparticles for Pulmonary Delivery. Colloids and Surfaces B: Biointerfaces, 81; 521–529
Amiruddin, R. M. A. and M. D. Hariyadi (2023). Effect of CaCl₂ Crosslinker Concentration on the Characteristics, Release and Stability of Ciprofloxacin HCl–Alginate–Carrageenan Microspheres. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia, 10(3); 312–323
Apridamayanti, P., N. N. Sinaga, and R. Desnita (2020). Comparison Ability of Polymers Acrycoat S100 and HPMC K4M to Entrapment Efficiency Domperidone in Microspheres. Indonesian Journal of Pharmaceutical Science and Technology, 7(1); 9–14
Bakhsi, M., F. Ebrahimi, S. Nazarian, J. Zargan, F. Behzadi, and D. S. Gariz (2017). Nano-Encapsulation of Chicken Immunoglobulin (IgY) in Sodium Alginate Nanoparticles: In Vitro Characterization. Biologicals, 30; 1–7
Dashora, K., S. Saraf, and S. Saraf (2007). Effect of Processing Variables and In Vitro Study of Microparticulate System of Nimesulide. Brazilian Journal of Pharmaceutical Sciences, 43(4); 555–562
Durgapal, D., S. Mukhopadhyay, and L. Goswami (2017). Preparation, Characterization and Evaluation of Floating Microparticles of Ciprofloxacin. International Journal of Applied Pharmaceutics, 9(1); 1–8
Fang, Y., N. Zhang, Q. Li, J. Chen, S. Xiong, and W. Pan (2019). Characterizing the Release Mechanism of Donepezil Loaded PLGA Microspheres In Vitro and In Vivo. Journal of Drug Delivery Science and Technology, 51; 430–437
Ferdiansyah, R., Y. D. Putri, S. Hamdani, and A. Julianto (2017). Increasing Solubility and Dissolution of Ibuprofen through the Formation of Microparticles Emulsification-Ionic-Gelation Method Using Polyvinyl Alcohol (PVA) as Polymer and Tripolyphosphate (TPP) as Crosslink Agent. Indonesian Journal of Pharmaceutical Science and Technology, 4(3); 118–133
Gavini, E., G. Rassu, V. Sanna, M. Cossu, and P. Giunchedi (2005). Mucoadhesive Microspheres for Nasal Administration of an Antiemetic Drug, Metoclopramide: In Vitro/Ex Vivo Studies. Journal of Pharmacy and Pharmacology, 57; 287–294
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; 3020–3027
Hariyadi, M. D., E. Hendradi, and V. L. O. Piay (2013). Optimization of Ovalbumin-Alginate Microspheres with Aerosolization Technique. PharmaScientia, 2(1); 21–30
Hariyadi, M. D. and N. Islam (2020). Current Status of Alginate in Drug Delivery. Advances in Pharmacological and Pharmaceutical Sciences; Article ID 8886095, 16 pages
Hariyadi, M. D., Y. Ma, Y. Wang, T. Bostrom, J. Malouf, M. S. Turner, B. Bhandari, and A. G. A. Coombes (2014). The Potential for the Production of Freeze-Dried Oral Vaccines Using Alginate Hydrogel Microspheres as Protein Carriers. Journal of Drug Delivery Science and Technology, 24(2); 178–184
Hariyadi, M. D., T. Purwanti, and S. Adilla (2018). Influence of Crosslinker Concentration on the Characteristics of Erythropoietin–Alginate Microspheres. Journal of Pharmacy and Pharmacognosy Research, 6(200); 250–259
Hazra, M., D. D. Mandal, T. Mandal, S. Bhuniya, and M. Ghosh (2015). Designing a Polymeric Microparticulate Drug Delivery System for Hydrophobic Drug Quercetin. Saudi Pharmaceutical Journal, 23(23); 429–436S
Jin, M., Y. Zheng, and Q. Hu (2009). Preparation and Characterization of Bovine Serum Albumin Alginate/Chitosan Microspheres for Oral Administration. Asian Journal of Pharmaceutical Sciences, 4(4); 215–220
Jung, H., Y. J. Lee, and W. B. Yoon (2018). Effect of Moisture Content on the Grinding Process and Powder Properties in Food: A Review. Processes, 6(6); 69
Kadam, N. R. and V. Suvarna (2015). Microspheres: A Brief Review. Asian Journal of Biomedical and Pharmaceutical Sciences, 5(47); 13–19
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. JFIKI, 9(2); 107–114
Khadka, P., J. Dummer, P. C. Hill, R. Katare, and S. C. Das (2022). A Review of Formulations and Preclinical Studies of Inhaled Rifampicin for Its Clinical Translation. Drug Delivery and Translational Research, 13(5); 1246–1271
Kumar, B. P., I. S. Chandiran, B. Bhavya, and M. Sindhuri (2011). Microparticulate Drug Delivery System: A Review. Indian Journal of Pharmaceutical Science & Research, 1(1); 19–37
Kurniawan, M. F., D. Setyawan, and D. M. Hariyadi (2024). Quercetin in Drug Carriers: Polymer Composite, Physical Characteristics, and In Vitro Study. Journal of Science and Technology Indonesia, 9(2); 380–412
Lakshmana, P. S., A. A. Shirwaikar, A. Shirwaikar, and A. Kumar (2009). Formulation and Evaluation of Sustained Release Microspheres of Rosin Containing Aceclofenac. Ars Pharm, 50; 51–62
Mandal, S., S. S. Kumar, B. Krishnamoorthy, and S. K. Basu (2010). Development and Evaluation of Calcium Alginate Beads Prepared by Sequential and Simultaneous Methods. Brazilian Journal of Pharmaceutical Sciences, 46; 785–793
Manjanna, K. M., T. M. P. Kumar, and B. Shivakumar (2010). Calcium Alginate Cross-Linked Polymeric Microbeads for Oral Sustained Drug Delivery in Arthritis. Drug Discoveries and Therapeutics, 4(2); 109–122
Nahrowi, R., S. Solehati, W. Widyastuti, N. L. G. R. Juliasih, K. D. Pandiangan, A. Setiawan, and J. Hendri (2024). New Encapsulation of Fucoxanthin Isolated from Cyclotella striata by Nano Chitosan–Pectin Using Ionic Gelation Method. Journal of Science and Technology Indonesia, 9(3); 517–528
Paranjpe, M. and C. M. C. Goymann (2014). Nanoparticle-Mediated Pulmonary Drug Delivery: A Review. International Journal of Molecular Sciences, 15; 5852–5873
Patil, S. B. and K. K. Sawant (2009). Development, Optimization, and In Vitro Evaluation of Alginate Mucoadhesive Microspheres of Carvedilol for Nasal Delivery. Journal of Microencapsulation, 26(5); 432–443
Patricia, B. (2020). Effect of Providing Health Belief Model Education to Pulmonary Tuberculosis Sufferers on Knowledge and Perception of Treatment Adherence. Gema Health Environment, 18(1); 58–64
Purwanti, T., W. Soeratri, and M. Zainudin (2018). Characterization of Nisin Microspheres with Combination Matrix Sodium Alginate–Gelatin. International Journal of Pharma Research and Health Sciences, 6(6); 2838–2843
Qureshi, D., S. K. Nayak, S. Maji, D. Kim, I. Banerjee, and K. Pal (2019). Carrageenan: A Wonder Polymer from Marine Algae for Potential Drug Delivery Application. Current Pharmaceutical Design, 12; 1172–1186
Rajabnezhad, S., L. Casettari, J. Lam, N. Alireza, T. Mohammad, P. Giovanni, and D. Mohammad (2016). Pulmonary Delivery of Rifampicin Microspheres Using Lower Generation Polyamidoamine Dendrimers as a Carrier. Powder Technology, 291; 366–374
Rani, Y. D. E., M. Rahmadi, and D. M. Hariyadi (2024). Development of Natural Polymer-Based Inhaled Microspheres for Tuberculosis. Pharmacy Education, 24(3); 123–128
Rastogi, R., Y. Sultana, M. Aqil, A. Ali, S. Kumar, K. Chuttani, and A. K. Mishra (2007). Alginate Microspheres of Isoniazid for Oral Sustained Drug Delivery. International Journal of Pharmaceutics, 334; 71–77
Rey, L. and J. C. May (2004). Freeze-Drying/Lyophilization of Pharmaceutical & Biological Products, Revised and Expanded. CRC Press
Rui, N. (2016). Nanocrystals Embedded in Chitosan-Based Respirable Swellable Microparticles as Dry Powder for Sustained Pulmonary Drug Delivery. European Journal of Pharmaceutical Sciences, 99; 137–146
Taneja, N. K. and J. S. Tyagi (2007). Resazurin Reduction Assays for Screening of Anti-Tubercular Compounds Against Dormant and Actively Growing Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis. Journal of Antimicrobial Chemotherapy, 60(2); 288–293
Uyen, N., Z. Hamid, N. Tram, and N. Ahmad (2019). Fabrication of Alginate Microspheres for Drug Delivery: A Review. International Journal of Biological Macromolecules, 153; 1035–1046
Vishwa, B., A. Moin, D. V. Gowda, S. M. D. Rizvi, W. A. H. Hegazy, A. S. Abu Lila, E. S. Khafagy, and A. N. Allam (2021). Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis. Pharmaceutics, 13(1); 79
Alipour, S., H. Montaseri, and M. Tafaghodi (2010). Preparation and Characterization of Biodegradable Paclitaxel-Loaded Alginate Microparticles for Pulmonary Delivery. Colloids and Surfaces B: Biointerfaces, 81; 521–529
Amiruddin, R. M. A. and M. D. Hariyadi (2023). Effect of CaCl₂ Crosslinker Concentration on the Characteristics, Release and Stability of Ciprofloxacin HCl–Alginate–Carrageenan Microspheres. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia, 10(3); 312–323
Apridamayanti, P., N. N. Sinaga, and R. Desnita (2020). Comparison Ability of Polymers Acrycoat S100 and HPMC K4M to Entrapment Efficiency Domperidone in Microspheres. Indonesian Journal of Pharmaceutical Science and Technology, 7(1); 9–14
Bakhsi, M., F. Ebrahimi, S. Nazarian, J. Zargan, F. Behzadi, and D. S. Gariz (2017). Nano-Encapsulation of Chicken Immunoglobulin (IgY) in Sodium Alginate Nanoparticles: In Vitro Characterization. Biologicals, 30; 1–7
Dashora, K., S. Saraf, and S. Saraf (2007). Effect of Processing Variables and In Vitro Study of Microparticulate System of Nimesulide. Brazilian Journal of Pharmaceutical Sciences, 43(4); 555–562
Durgapal, D., S. Mukhopadhyay, and L. Goswami (2017). Preparation, Characterization and Evaluation of Floating Microparticles of Ciprofloxacin. International Journal of Applied Pharmaceutics, 9(1); 1–8
Fang, Y., N. Zhang, Q. Li, J. Chen, S. Xiong, and W. Pan (2019). Characterizing the Release Mechanism of Donepezil Loaded PLGA Microspheres In Vitro and In Vivo. Journal of Drug Delivery Science and Technology, 51; 430–437
Ferdiansyah, R., Y. D. Putri, S. Hamdani, and A. Julianto (2017). Increasing Solubility and Dissolution of Ibuprofen through the Formation of Microparticles Emulsification-Ionic-Gelation Method Using Polyvinyl Alcohol (PVA) as Polymer and Tripolyphosphate (TPP) as Crosslink Agent. Indonesian Journal of Pharmaceutical Science and Technology, 4(3); 118–133
Gavini, E., G. Rassu, V. Sanna, M. Cossu, and P. Giunchedi (2005). Mucoadhesive Microspheres for Nasal Administration of an Antiemetic Drug, Metoclopramide: In Vitro/Ex Vivo Studies. Journal of Pharmacy and Pharmacology, 57; 287–294
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; 3020–3027
Hariyadi, M. D., E. Hendradi, and V. L. O. Piay (2013). Optimization of Ovalbumin-Alginate Microspheres with Aerosolization Technique. PharmaScientia, 2(1); 21–30
Hariyadi, M. D. and N. Islam (2020). Current Status of Alginate in Drug Delivery. Advances in Pharmacological and Pharmaceutical Sciences; Article ID 8886095, 16 pages
Hariyadi, M. D., Y. Ma, Y. Wang, T. Bostrom, J. Malouf, M. S. Turner, B. Bhandari, and A. G. A. Coombes (2014). The Potential for the Production of Freeze-Dried Oral Vaccines Using Alginate Hydrogel Microspheres as Protein Carriers. Journal of Drug Delivery Science and Technology, 24(2); 178–184
Hariyadi, M. D., T. Purwanti, and S. Adilla (2018). Influence of Crosslinker Concentration on the Characteristics of Erythropoietin–Alginate Microspheres. Journal of Pharmacy and Pharmacognosy Research, 6(200); 250–259
Hazra, M., D. D. Mandal, T. Mandal, S. Bhuniya, and M. Ghosh (2015). Designing a Polymeric Microparticulate Drug Delivery System for Hydrophobic Drug Quercetin. Saudi Pharmaceutical Journal, 23(23); 429–436S
Jin, M., Y. Zheng, and Q. Hu (2009). Preparation and Characterization of Bovine Serum Albumin Alginate/Chitosan Microspheres for Oral Administration. Asian Journal of Pharmaceutical Sciences, 4(4); 215–220
Jung, H., Y. J. Lee, and W. B. Yoon (2018). Effect of Moisture Content on the Grinding Process and Powder Properties in Food: A Review. Processes, 6(6); 69
Kadam, N. R. and V. Suvarna (2015). Microspheres: A Brief Review. Asian Journal of Biomedical and Pharmaceutical Sciences, 5(47); 13–19
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. JFIKI, 9(2); 107–114
Khadka, P., J. Dummer, P. C. Hill, R. Katare, and S. C. Das (2022). A Review of Formulations and Preclinical Studies of Inhaled Rifampicin for Its Clinical Translation. Drug Delivery and Translational Research, 13(5); 1246–1271
Kumar, B. P., I. S. Chandiran, B. Bhavya, and M. Sindhuri (2011). Microparticulate Drug Delivery System: A Review. Indian Journal of Pharmaceutical Science & Research, 1(1); 19–37
Kurniawan, M. F., D. Setyawan, and D. M. Hariyadi (2024). Quercetin in Drug Carriers: Polymer Composite, Physical Characteristics, and In Vitro Study. Journal of Science and Technology Indonesia, 9(2); 380–412
Lakshmana, P. S., A. A. Shirwaikar, A. Shirwaikar, and A. Kumar (2009). Formulation and Evaluation of Sustained Release Microspheres of Rosin Containing Aceclofenac. Ars Pharm, 50; 51–62
Mandal, S., S. S. Kumar, B. Krishnamoorthy, and S. K. Basu (2010). Development and Evaluation of Calcium Alginate Beads Prepared by Sequential and Simultaneous Methods. Brazilian Journal of Pharmaceutical Sciences, 46; 785–793
Manjanna, K. M., T. M. P. Kumar, and B. Shivakumar (2010). Calcium Alginate Cross-Linked Polymeric Microbeads for Oral Sustained Drug Delivery in Arthritis. Drug Discoveries and Therapeutics, 4(2); 109–122
Nahrowi, R., S. Solehati, W. Widyastuti, N. L. G. R. Juliasih, K. D. Pandiangan, A. Setiawan, and J. Hendri (2024). New Encapsulation of Fucoxanthin Isolated from Cyclotella striata by Nano Chitosan–Pectin Using Ionic Gelation Method. Journal of Science and Technology Indonesia, 9(3); 517–528
Paranjpe, M. and C. M. C. Goymann (2014). Nanoparticle-Mediated Pulmonary Drug Delivery: A Review. International Journal of Molecular Sciences, 15; 5852–5873
Patil, S. B. and K. K. Sawant (2009). Development, Optimization, and In Vitro Evaluation of Alginate Mucoadhesive Microspheres of Carvedilol for Nasal Delivery. Journal of Microencapsulation, 26(5); 432–443
Patricia, B. (2020). Effect of Providing Health Belief Model Education to Pulmonary Tuberculosis Sufferers on Knowledge and Perception of Treatment Adherence. Gema Health Environment, 18(1); 58–64
Purwanti, T., W. Soeratri, and M. Zainudin (2018). Characterization of Nisin Microspheres with Combination Matrix Sodium Alginate–Gelatin. International Journal of Pharma Research and Health Sciences, 6(6); 2838–2843
Qureshi, D., S. K. Nayak, S. Maji, D. Kim, I. Banerjee, and K. Pal (2019). Carrageenan: A Wonder Polymer from Marine Algae for Potential Drug Delivery Application. Current Pharmaceutical Design, 12; 1172–1186
Rajabnezhad, S., L. Casettari, J. Lam, N. Alireza, T. Mohammad, P. Giovanni, and D. Mohammad (2016). Pulmonary Delivery of Rifampicin Microspheres Using Lower Generation Polyamidoamine Dendrimers as a Carrier. Powder Technology, 291; 366–374
Rani, Y. D. E., M. Rahmadi, and D. M. Hariyadi (2024). Development of Natural Polymer-Based Inhaled Microspheres for Tuberculosis. Pharmacy Education, 24(3); 123–128
Rastogi, R., Y. Sultana, M. Aqil, A. Ali, S. Kumar, K. Chuttani, and A. K. Mishra (2007). Alginate Microspheres of Isoniazid for Oral Sustained Drug Delivery. International Journal of Pharmaceutics, 334; 71–77
Rey, L. and J. C. May (2004). Freeze-Drying/Lyophilization of Pharmaceutical & Biological Products, Revised and Expanded. CRC Press
Rui, N. (2016). Nanocrystals Embedded in Chitosan-Based Respirable Swellable Microparticles as Dry Powder for Sustained Pulmonary Drug Delivery. European Journal of Pharmaceutical Sciences, 99; 137–146
Taneja, N. K. and J. S. Tyagi (2007). Resazurin Reduction Assays for Screening of Anti-Tubercular Compounds Against Dormant and Actively Growing Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium smegmatis. Journal of Antimicrobial Chemotherapy, 60(2); 288–293
Uyen, N., Z. Hamid, N. Tram, and N. Ahmad (2019). Fabrication of Alginate Microspheres for Drug Delivery: A Review. International Journal of Biological Macromolecules, 153; 1035–1046
Vishwa, B., A. Moin, D. V. Gowda, S. M. D. Rizvi, W. A. H. Hegazy, A. S. Abu Lila, E. S. Khafagy, and A. N. Allam (2021). Pulmonary Targeting of Inhalable Moxifloxacin Microspheres for Effective Management of Tuberculosis. Pharmaceutics, 13(1); 79
Authors
Liempepas, A., Rahmadi, M., Ifadotunnikmah, F., & Hariyadi, D. M. . (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. https://doi.org/10.26554/sti.2025.10.3.817-825
This work is licensed under a Creative Commons Attribution 4.0 International License.