STM Journals Peer-reviewed research from Consortium e-Learning Network

Journal of Polymer & Composites Review Article

Carboxymethyl Cellulose-Based Spray-Dried Microspheres: Recent Advances and Applications in Targeted Drug Delivery Systems

  1. Saravanan Muniyandy Department of Pharmacy, Fatima College of Health Sciences, Al Mafraq

Abstract

Microspheres are spherical particles ranging from 1 to 1000 μm, made from natural or synthetic polymers and inorganic materials. Their structure allows precise drug delivery, improving targeted release and minimizing off-target effects. Natural polymers such as starch, chitosan, and alginate are favored for their biodegradability, adhesion, and compatibility, enhancing mucosal interaction and residence time. Microspheres are widely used in site-specific drug delivery, gene therapy, and vaccine administration, improving immunogenicity, extending drug release, and increasing safety. This review addresses gaps in previous literature, particularly in natural polymer-based delivery and gene therapy applications. It highlights recent advancements and evolving technologies, providing an updated analysis of microspheres in targeted and sustained drug delivery systems. The article focuses on Carboxymethyl Cellulose (CMC)--based spray-dried microspheres, emphasizing spray drying and exploring CMC's chemical structure, substitution level, and physicochemical properties. Key process variables like atomization, feed rate, drying gases, and their influence on particle morphology and size distribution are discussed. The review also addresses drug-polymer interactions, stabilizers, cross-linkers, and parameters like drug loading, entrapment efficiency, surface charge, swelling, porosity, and in-vitro release kinetics. Analytical techniques such as FTIR and density determination are presented, assessing the stability and pharmaceutical applications of CMC-based microspheres. The review aims to offer a comprehensive, updated analysis of recent advancements, integrating emerging trends and novel therapeutic approaches to bridge previous gaps and respond to evolving clinical needs and technological progress in drug delivery systems.

Keywords

References (49)

  1. Xue R, Wu H, Li S, Pu N, Wei D, Zhao N, et al. Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball. Materials Today Bio. 2024;27:101126. doi:10.1016/j.mtbio.2024.101126
  2. Deshmukh R, Wagh P, Naik J. Solvent evaporation and spray drying technique for micro- and nanospheres/particles preparation: A review. Drying Technology. 2016;34(15):1758-1772. doi:10.1080/07373937.2016.1232271
  3. Kumar R, Thakur AK, Chaudhari P, Banerjee N. Particle Size Reduction Techniques of Pharmaceutical Compounds for the Enhancement of Their Dissolution Rate and Bioavailability. Journal of Pharmaceutical Innovation. 2021;17(2):333-352. doi:10.1007/s12247-020-09530-5
  4. Gupta T, Singh J, Kaur S, Sandhu S, Singh G, Kaur IP. Enhancing Bioavailability and Stability of Curcumin Using Solid Lipid Nanoparticles (CLEN): A Covenant for Its Effectiveness. Frontiers in Bioengineering and Biotechnology. 2020;8. doi:10.3389/fbioe.2020.00879
  5. Balaure PC, Grumezescu AM. Recent Advances in Surface Nanoengineering for Biofilm Prevention and Control. Part I: Molecular Basis of Biofilm Recalcitrance. Passive Anti-Biofouling Nanocoatings. Nanomaterials. 2020;10(6):1230. doi:10.3390/nano10061230
  6. Yang Y, Nan W, Zhang R, Shen S, Wu M, Zhong S, et al. Fabrication of carboxymethyl cellulose-based thermo-sensitive hydrogels and inhibition of corneal neovascularization. International Journal of Biological Macromolecules. 2024;261:129933. doi:10.1016/j.ijbiomac.2024.129933
  7. Souhoka FA, Latupeirissa J. Synthesis of carboxymethyl cellulose (CMC) using sonochemistry technique. AIP Conference Proceedings. 2023;2588:020013. doi:10.1063/5.0111831
  8. Peng D, Jin W, Arts M, Yang J, Li B, Sagis LMC. Effect of CMC degree of substitution and gliadin/CMC ratio on surface rheology and foaming behavior of gliadin/CMC nanoparticles. Food Hydrocolloids. 2020;107:105955. doi:10.1016/j.foodhyd.2020.105955
  9. Pushpamalar V, Langford SJ, Ahmad M, Lim YY. Optimization of reaction conditions for preparing carboxymethyl cellulose from sago waste. Carbohydrate Polymers. 2006;64(2):312-318. doi:10.1016/j.carbpol.2005.12.003
  10. Ghannam MT, Esmail MN. Experimental study on wetting of fibers with non‐Newtonian liquids. AIChE Journal. 1997;43(6):1579-1588. doi:10.1002/aic.690430621
  11. Wolska E. Fine powder of lipid microparticles – spray drying process development and optimization. Journal of Drug Delivery Science and Technology. 2021;64:102640. doi:10.1016/j.jddst.2021.102640
  12. Hernandez B, Mondragon R, Pinto MA, Hernandez L, Julia JE, Jarque JC, et al. Single droplet drying of detergents: Experimentation and modelling. Particuology. 2021;58:35-47. doi:10.1016/j.partic.2021.01.012
  13. Salama AH. Spray drying as an advantageous strategy for enhancing pharmaceuticals bioavailability. Drug Delivery and Translational Research. 2019;10(1):1-12. doi:10.1007/s13346-019-00648-9
  14. Pilcer G, Rosière R, Traina K, Sebti T, Vanderbist F, Amighi K. New Co-Spray-Dried Tobramycin Nanoparticles-Clarithromycin Inhaled Powder Systems for Lung Infection Therapy in Cystic Fibrosis Patients. Journal of Pharmaceutical Sciences. 2013;102(6):1836-1846. doi:10.1002/jps.23525
  15. Ledet GA, Graves RA, Bostanian LA, Mandal TK. Spray-Drying of Biopharmaceuticals. Lyophilized Biologics and Vaccines. 2015:273-297. doi:10.1007/978-1-4939-2383-0_12
  16. Ulusoy U. A Review of Particle Shape Effects on Material Properties for Various Engineering Applications: From Macro to Nanoscale. Minerals. 2023;13(1):91. doi:10.3390/min13010091
  17. Pandey NK, Singh SK, Gulati M, Kumar B, Kapoor B, Ghosh D, et al. Overcoming the dissolution rate, gastrointestinal permeability and oral bioavailability of glimepiride and simvastatin co-delivered in the form of nanosuspension and solid self-nanoemulsifying drug delivery system: A comparative study. Journal of Drug Delivery Science and Technology. 2020;60:102083. doi:10.1016/j.jddst.2020.102083
  18. Zhao T, Chen C, Liu X, Hao J. Effect of gas Mach number on the flow field of close-coupled gas atomization, particle size and cooling rate of as-atomized powder: Simulation and experiment. Advanced Powder Technology. 2023;34(5):104007. doi:10.1016/j.apt.2023.104007
  19. Corzo C, Fuchsbichler A, Savencu I, Afonso Urich J, Zimmer A, Lochmann D, et al. Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability. International Journal of Pharmaceutics. 2021;610:121259. doi:10.1016/j.ijpharm.2021.121259
  20. Dobry DE, Settell DM, Baumann JM, Ray RJ, Graham LJ, Beyerinck RA. A Model-Based Methodology for Spray-Drying Process Development. Journal of Pharmaceutical Innovation. 2009;4(3):133-142. doi:10.1007/s12247-009-9064-4
  21. Maltesen MJ, van de Weert M, Grohganz H. Design of Experiments-Based Monitoring of Critical Quality Attributes for the Spray-Drying Process of Insulin by NIR Spectroscopy. AAPS PharmSciTech. 2012;13(3):747-755. doi:10.1208/s12249-012-9796-1
  22. Paluch KJ, Tajber L, Corrigan OI, Healy AM. Impact of process variables on the micromeritic and physicochemical properties of spray-dried porous microparticles, part I: introduction of a new morphology classification system. Journal of Pharmacy and Pharmacology. 2012;64(11):1570-1582. doi:10.1111/j.2042-7158.2012.01539.x
  23. Paluch KJ, Tajber L, Adamczyk B, Corrigan OI, Healy AM. A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability. International Journal of Pharmaceutics. 2012;436(1-2):873-876. doi:10.1016/j.ijpharm.2012.05.074
  24. Druel L, Kenkel A, Baudron V, Buwalda S, Budtova T. Cellulose Aerogel Microparticles via Emulsion-Coagulation Technique. Biomacromolecules. 2020;21(5):1824-1831. doi:10.1021/acs.biomac.9b01725
  25. Limpongsa E, Soe MT, Jaipakdee N. Modification of release and penetration behavior of water-soluble active ingredient from ball-milled glutinous starch matrix via carboxymethylcellulose blending. International Journal of Biological Macromolecules. 2021;193:2271-2280. doi:10.1016/j.ijbiomac.2021.11.059
  26. Ahmad A, Mubarak NM, Jannat FT, Ashfaq T, Santulli C, Rizwan M, et al. A Critical Review on the Synthesis of Natural Sodium Alginate Based Composite Materials: An Innovative Biological Polymer for Biomedical Delivery Applications. Processes. 2021;9(1):137. doi:10.3390/pr9010137
  27. Silva TM, Oliveira ACDJ, Leão AD, Ramos RKLG, Chaves LL, Silva-Filho ECD, et al. Cashew gum as future multipurpose biomacromolecules. Carbohydrate Polymers. 2025;347:122749. doi:10.1016/j.carbpol.2024.122749
  28. Kumar M, Singh V, Choudhary R, kumar deb D, Singh S, Srivastava A. Mixed Micellization of drug-excipients and its application to enhance the binding and encapsulation efficacy of ibuprofen in aqueous media. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2021;628:127268. doi:10.1016/j.colsurfa.2021.127268
  29. Patel P, Agrawal Y. Preparation and In-vitro Evaluation of Levan Micelles: A Polyfructan Based Nano-carrier for Breast Cancer Targeted Delivery. Drug Delivery Letters. 2019;9(2):97-107. doi:10.2174/2210303109666190102115814
  30. Lee S, Li L, Ben-Aryeh Y, Wang Z, Guo W. Overcoming the diffraction limit induced by microsphere optical nanoscopy. Journal of Optics. 2013;15(12):125710. doi:10.1088/2040-8978/15/12/125710
  31. Rajaonarivony M, Vauthier C, Couarraze G, Puisieux F, Couvreur P. Development of a New Drug Carrier Made from Alginate. Journal of Pharmaceutical Sciences. 1993;82(9):912-917. doi:10.1002/jps.2600820909
  32. Sakthivel T, Guruvayoorappan C. Immunomodulatory activity of Capparis sepiaria L. on humoral and cell-mediated immune response in rats. Int J Pharm Sci Rev Res 2015;31(1):94 8.
  33. Yousefi H, Faezipour M, Hedjazi S, et al. Comparative study of drying techniques for the production of cellulose nanofibers from raw and pretreated wood pulps. Dry Technol. 2011;29(2):205-215.
  34. Kumar S, Malhotra R, Kumar D, et al. Formulation and evaluation of mouth dissolving tablets of clozapine using coprocessed superdisintegrants. Sci Pharm 2016;84(1):1-16.
  35. Patel JK, Patel RP, Amin AF, Patel MM. Formulation and evaluation of mucoadhesive glipizide microspheres. AAPS PharmSciTech. 2005;6(1):E49-E55. doi:10.1208/pt060110
  36. Hassan MS, Patel MJ. Evaluation of CMC-based spray-dried microspheres for controlled drug delivery. J. Pharm. Sci. Res., 1, 47-53 (2010)
  37. Singh B, Sharma N, Ahuja N. Development of biodegradable microspheres for controlled delivery of losartan potassium. Microencapsul., 27, 63-74 (2010).
  38. Bodmeier R, Chen H. Indomethacin polymeric nanosuspensions prepared by microfluidization. Pharm. Sci., 79, 1009-1012 (1990).
  39. Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy. Advanced Drug Delivery Reviews. 2001;47(1):3-19. doi:10.1016/s0169-409x(00)00118-6
  40. Sakthivel T, Habeebuddin M, Devi MV. Formulation and in vitro evaluation of spray dried microspheres of anti-diabetic drug. J. Pharm. Sci. Rev. Res., 31, 94-98 (2015).
  41. Patel JK, Patel RP, Amin AF, Patel MM. Formulation and evaluation of mucoadhesive glipizide microspheres. AAPS PharmSciTech. 2005;6(1):E49-E55. doi:10.1208/pt060110
  42. Müller G, Schneider M, Biemer-Daub G, Wied S. Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cellular Signalling. 2011;23(7):1207-1223. doi:10.1016/j.cellsig.2011.03.013
  43. Ghernaout D, Al-Ghonamy AI, Boucherit A, et al. Brownian motion and coagulation process. Am J Environ Prot. 2015 Apr 29;4(5-1):1-5.
  44. Che Nan NF, Zainuddin N, Ahmad M. Preparation and Swelling Study of CMC Hydrogel as Potential Superabsorbent. Pertanika J Sci Technol. 2019 Jan 1;27(1).
  45. Jain M, Koren S, Miga KH, Quick J, Rand AC, Sasani TA, et al. Nanopore sequencing and assembly of a human genome with ultra-long reads. Nature Biotechnology. 2018;36(4):338-345. doi:10.1038/nbt.4060
  46. Rahman MR, Hamdan S, Ahmed AS, Islam MS, Talib ZA, Abdullah WFW, et al. Thermogravimetric analysis and dynamic Young's modulus measurement of N , N ‐dimethylacetamide‐impregnated wood polymer composites. Journal of Vinyl and Additive Technology. 2011;17(3):177-183. doi:10.1002/vnl.20275
  47. Weng L, Rostamzadeh P, Nooryshokry N, Le HC, Golzarian J. In vitro and in vivo evaluation of biodegradable embolic microspheres with tunable anticancer drug release. Acta Biomaterialia. 2013;9(6):6823-6833. doi:10.1016/j.actbio.2013.02.017
  48. Sturm R. A three-dimensional model of tracheobronchial particle distribution during mucociliary clearance in the human respiratory tract. Zeitschrift für Medizinische Physik. 2013;23(2):111-119. doi:10.1016/j.zemedi.2013.02.004
  49. Yoshida H, Morita T, Abe Y, Inagaki A, Tomita N, Izutsu KI, et al. Effects of Apex Size on Dissolution Profiles in the USP II Paddle Apparatus. AAPS PharmSciTech. 2023;25(1). doi:10.1208/s12249-023-02722-5
Support