Physicochemical Characterization and Drug Release Behavior of Theophylline with Chitosan–Alginate Polyelectrolyte Complexes Microparticle
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 309-316
https://doi.org/10.22037/ijps.v22i1.51511
Abstract
Theophylline is a methylxanthine alkaloid commonly used in the management of bronchial asthma; however, its clinical use is limited by a short biological half-life, gastric irritation, and an unpleasant bitter taste. Encapsulation of theophylline into polymeric microparticles has been proposed as an effective approach to improve its therapeutic performance by providing sustained drug release and reducing adverse gastrointestinal effects. This study investigated the influence of chitosan concentration on the physical characteristics, drug content, and in vitro release behavior of theophylline-loaded alginate–chitosan polyelectrolyte complex microparticles. Microparticles were prepared using the orifice–ionic gelation technique with sodium alginate and chitosan at ratios of 1:0.25, 1:0.50, and 1:1. The resulting microparticles were evaluated for morphology, particle-size distribution, chemical interactions, drug content, and in vitro drug-release profiles. An increase in chitosan concentration led to larger particle sizes and the formation of smoother, more spherical microparticles. The highest drug content was obtained at an alginate–chitosan ratio of 1:0.25. All formulations exhibited a sustained-release profile compared with pure theophylline, indicating effective drug encapsulation within the polymeric matrix. The slowest drug release was observed in the formulation containing the highest chitosan concentration (1:1 alginate–chitosan ratio). These findings suggest that alginate–chitosan polyelectrolyte complex microparticles are a promising delivery system for theophylline and that chitosan concentration plays a crucial role in controlling microparticle characteristics and drug-release behaviorTheophylline is a methylxanthine alkaloid commonly used in the management of bronchial asthma; however, its clinical use is limited by a short biological half-life, gastric irritation, and an unpleasant bitter taste. Encapsulation of theophylline into polymeric microparticles has been proposed as an effective approach to improve its therapeutic performance by providing sustained drug release and reducing adverse gastrointestinal effects. This study investigated the influence of chitosan concentration on the physical characteristics, drug content, and in vitro release behavior of theophylline-loaded alginate–chitosan polyelectrolyte complex microparticles. Microparticles were prepared using the orifice–ionic gelation technique with sodium alginate and chitosan at ratios of 1:0.25, 1:0.50, and 1:1. The resulting microparticles were evaluated for morphology, particle-size distribution, chemical interactions, drug content, and in vitro drug-release profiles. An increase in chitosan concentration led to larger particle sizes and the formation of smoother, more spherical microparticles. The highest drug content was obtained at an alginate–chitosan ratio of 1:0.25. All formulations exhibited a sustained-release profile compared with pure theophylline, indicating effective drug encapsulation within the polymeric matrix. The slowest drug release was observed in the formulation containing the highest chitosan concentration (1:1 alginate–chitosan ratio). These findings suggest that alginate–chitosan polyelectrolyte complex microparticles are a promising delivery system for theophylline and that chitosan concentration plays a crucial role in controlling microparticle characteristics and drug-release behavior.
- Theophylline
- Chitosan
- Microparticles
- Controlled release
- Polyelectrolyte complex
How to Cite
References
1. Sweetman SC. Martindale: The Complete Drug Reference. 36th ed. Pharmaceutical Press; 2009. 3709 p.
2. Wise DL. Handbook of Pharmaceutical Controlled Release Technology. 1st ed. Boca Raton: CRC Press; 2000.
3. Miyazaki Y, Onuki Y, Yakou S, Takayama K. Effect of temperature-increase rate on drug release characteristics of dextran microspheres prepared by emulsion solvent evaporation process. 2006;144–51.
4. Senthil SP, Senthilkumar KL, Chandi SR, Ezhilmuthu RP, Saravanan MM, Sandu NR. Formulation and Evaluation of Imatinib Mesylate Microspheres by Chemical Crosslinking Method. Res J Pharm Technol. 2012;5(7):934–7.
5. Birnbaum DT, Brannon-Peppas L. Microparticle Drug Delivery Systems. In: Brown DM, editor. Drug Delivery Systems in Cancer Therapy. Totowa, NJ: Humana Press; 2004. p. 117–35.
6. Swarbrick J. Encyclopedia of Pharmaceutical Technology. 3rd ed. New York: Informa Healthcare USA, Inc.; 2007. 2315–2325 p.
7. Parikh D. How to Optimize Fluid Bed Processing Technology. Pharmaceutical Process Technology Series; 2017. 210 p.
8. Rastogi R, Sultana Y, Aqil M, Ali A, Kumar S, Chuttani K. Alginate microspheres of isoniazid for oral sustained drug delivery. Int J Pharm. 2007;334(1):71–7.
9. Vandenberg GW, Drolet C, Scott SL, Noue J. Factors affecting protein release from alginate–chitosan coacervate microcapsules during production and gastric/intestinal simulation. J Control Release. 2001;77:297–307.
10. Chowdary KPR, Rao YS. Preparation and Evaluation of Mucoadhesive Microcapsules of Indomethacin. Indian J Pharm Sci. 2003;65(1):49–52.
11. Ko JA, Park HJ, Hwang SJ, Park JB, Lee JS. Preparation and characterization of chitosan microparticles intended for controlled drug delivery. Int J Pharm. 2002;249(1):165–74.
12. Sinha VR, Singla AK, Wadhawan S, Kaushik R, Kumria R, Bansal K. Chitosan microspheres as a potential carrier for drugs. Int J Pharm. 2004;274(1):1–33.
13. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5–28.
14. Irianto, Hari E, Muljanah I. Proses dan Aplikasi Nanopartikel Kitosan Sebagai Penghantar Obat. Squalen. 2011;6(1):1–8.
15. Naskar S, Koutsu K, Sharma S. Chitosan-based nanoparticles as drug delivery systems. J Drug Target. 2019;27(4):379–93. doi:10.1080/1061186X.2018.1513621
16. Suhail M, Li XR, Liu JY, Hsieh WC, Lin YW, Wu PC. Fabrication of alginate based microgels for drug-sustained release: In-vitro and in-vivo evaluation. Int J Biol Macromol [Internet]. 2021;192:958–66. doi:https://doi.org/10.1016/j.ijbiomac.2021.10.054
17. Cheng KC, Hu CC, Li CY, Li SC, Cai ZW, Wei Y. Theophylline-loaded pectin/chitosan hydrochloride submicron particles. Polymers (Basel). 2022;14(21). doi:10.3390/polym14214564
18. Al-assady NAH, Badran HA, Kamil SA, Abo-alhal RC. Preparation and evaluation in vitro release of sodium alginate / chitosan polyelectrolyte microparticles containing rifampicin and theoretical study using DFT methods. J Biomol Struct Dyn [Internet]. 2024;42(4):1795–811. doi:10.1080/07391102.2023.2202279
19. Wasupalli GK, Verma D. Molecular interactions in chitosan–alginate polyelectrolyte complexes. Int J Biol Macromol. 2018;114:10–7. doi:10.1016/j.ijbiomac.2018.03.083
20. Costa MPM, Prates LM, Baptista L, Cruz MTM, Ferreira ILM. Interaction of polyelectrolyte complex between sodium alginate and chitosan. Carbohydr Polym. 2018;198:51–60. doi:10.1016/j.carbpol.2018.06.036
21. Sankalia MG, Mashru RC, Sankalia JM, Sutariya VB. Reversed chitosan-alginate polyelectrolyte complex. Eur J Pharm Biopharm. 2007;65(2):215–32. doi:10.1016/j.ejpb.2006.08.009
22. Popa N, Novac O, Profire L, Hritcu D, Popa MI. Inclusion and release of theophylline from chitosan based microparticles. Turkish J Chem. 2010;34(2):255–62.
23. Obeidat WM, Gharaibeh SF, Jaradat A. Influence of drug solubility and formulation parameters on chitosan-TPP nanoparticles. AAPS PharmSciTech. 2022;23(7). doi:10.1208/s12249-022-02368-6
24. Sreekumar S, Goycoolea FM, Moerschbacher BM, Rivera-Rodriguez GR. Parameters influencing the size of chitosan-TPP particles. Sci Rep. 2018;8(1). doi:10.1038/s41598-018-26389-4
25. Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge and particle size of chitosan-TPP nanoparticles. Colloids Surfaces B. 2005;44:65–73. doi:10.1016/j.colsurfb.2005.06.001
26. Roy H, Nayak BS, Maddiboyina B, Nandi S. Chitosan based urapidil microparticle development. J Drug Deliv Sci Technol. 2022;76. doi:10.1016/j.jddst.2022.103745
27. Sedyakina N, Kuskov A, Velonia K, Feldman N, Lutsenko S, Avramenko G. Modulation of entrapment efficiency of BSA-loaded chitosan microparticles. Materials (Basel). 2020;13(8). doi:10.3390/ma13081806.
- Abstract Viewed: 27 times
- IJPS_Volume22_Issue1_Pages309-316 Downloaded: 16 times