Sustained Release Microspheres in Drug Delivery: Formulation Strategies, Characterization, and Therapeutic Application

Authors

  • Tusara Kanta Behera Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Santosh Kumar Dash Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Jyotirmaya Parida Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Khagesh Bhoi Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Lokesh Kumar Barik Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Madhusudan Behera Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Jitu Rout Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Kandarpa Rana Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.
  • Kundan Bishi Department of Pharmaceutics, the Pharmaceutical College, Samleswari Vihar, Tingipali, Barpali, Odisha.

DOI:

https://doi.org/10.22270/ajprd.v14i2.1736

Abstract

Sustained release microspheres have emerged as a promising and versatile drug delivery system capable of improving therapeutic efficacy, patient compliance, and overall treatment outcomes by providing controlled and prolonged drug release. These microspheres, typically composed of biodegradable and biocompatible polymers such as PLGA, PLA, chitosan, and alginate, are designed to encapsulate a wide range of drugs, including small molecules, peptides, and proteins, and release them at a predetermined rate over extended periods. Various formulation strategies such as solvent evaporation, spray drying, ionic gelation, coacervation, and advanced techniques like microfluidics have been extensively explored to optimize particle size, drug loading, and release characteristics. Comprehensive characterization of microspheres, including particle size analysis, surface morphology, encapsulation efficiency, thermal behavior, and in vitro drug release studies, plays a critical role in ensuring formulation stability and performance. Drug release from microspheres is governed by mechanisms such as diffusion, degradation, swelling, and erosion, which can be effectively, modeled using kinetic approaches like zero-order, Higuchi, and Korsmeyer peppas models. These systems have demonstrated significant potential across diverse therapeutic areas, including cancer therapy, diabetes management, cardiovascular diseases, infectious diseases, hormone delivery, vaccine delivery, and central nervous system disorders, with several formulations already approved for clinical use. Furthermore, recent advancements in targeted delivery, stimuli responsive systems, and nanostructured microspheres, along with integration of Quality by Design (QbD) and artificial intelligence approaches, have further expanded their application scope. Despite challenges such as burst release, scale-up difficulties, and regulatory considerations, sustained release microspheres continue to represent a cornerstone in modern pharmaceutics, offering innovative solutions for controlled and site-specific drug delivery.

 

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References

Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004 Mar 19;303(5665):1818-22.

Siepmann J, Siepmann F. Modeling of diffusion controlled drug delivery. Journal of controlled release. 2012 Jul 20;161(2):351-62.

Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004 Mar 19;303(5665):1818-22.

Colombo P. Swelling-controlled release in hydrogel matrices for oral route. Advanced Drug Delivery Reviews. 1993 Jul 1;11(1-2):37-57.

Freiberg S, Zhu XX. Polymer microspheres for controlled drug release. International journal of pharmaceutics. 2004 Sep 10;282(1-2):1-8.

Jain NK, editor. Controlled and novel drug delivery. New Delhi: CBS publishers & distributors; 1997.

Kreuter J. Nanoparticles and microparticles for drug and vaccine delivery. Journal of anatomy. 1996 Dec;189(Pt 3):503.

Chien YW. Novel Drug Delivery Systems. 2nd ed. New York: Marcel Dekker; 1992.

Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217–223.

Fu Y, Kao WJ. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert opinion on drug delivery. 2010 Apr 1;7(4):429-44.

Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011 Sep;3(3):1377-97.

Patil NV, Wadd NV, Thorat SS, Upadhye SS. Microspheres: A novel drug delivery system. Am. J. PharmTech Res. 2020;10(02):286-301.

Sahil K, Akanksha M, Premjeet S, Bilandi A, Kapoor B. Microsphere: A review. Int. J. Res. Pharm. Chem. 2011;1(4):1184-98.

Sharma M, Dev SK, Kumar M, Shukla AK. Microspheres as suitable drug carrier in sustained release drug delivery: an overview. Asian Journal of Pharmacy And Pharmacology. 2018;4(2):102-8.

Danhier, F., Ansorena, E., Silva, J. M., Coco, R., Le Breton, A., & Préat, V. (2012).PLGA-based nanoparticles: An overview of biomedical applications. Journal of Controlled Release, 161(2), 505–522. https://doi.org/10.1016/j.jconrel.2012.01.043

Qiu, Y., Chen, Y., Zhang, G. G. Z., Liu, L., & Porter, W. (2016).

Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice (2nd ed.).

Academic Press.

Patil, J. S., Kamalapur, M. V., Marapur, S. C., & Kadam, D. V. (2018).

Ionotropic gelation and polyelectrolyte complexation: The novel techniques to design hydrogel particulate sustained drug delivery systems. Digest Journal of Nanomaterials and Biostructures, 13(1), 149–160.

Pawar, V. K., Kansal, S., Garg, G., Awasthi, R., Singodia, D., & Kulkarni, G. T. (2020). Gastroretentive dosage forms: A review with special emphasis on floating drug delivery systems. Drug Delivery, 27(1), 113–129. https://doi.org/10.1080/10717544.2019.1709955

Alexiou, C., Schmid, R. J., Jurgons, R., Kremer, M., Wanner, G., Bergemann, C., Huenges, E., Nawroth, T., Arnold, W., & Parak, F. G. (2011). Targeting cancer cells: Magnetic nanoparticles as drug carriers. European Biophysics Journal, 40(4), 453–460.

https://doi.org/10.1007/s00249-010-0640-0

Li, J., & Mooney, D. J. (2016). Designing hydrogels for controlled drug delivery. Nature Reviews Materials, 1, 16071. https://doi.org/10.1038/natrevmats.2016.71

Siepmann, J., & Siepmann, F. (2012). Modeling of diffusion controlled drug delivery. Journal of Controlled Release, 161(2), 351–362. https://doi.org/10.1016/j.jconrel.2011.10.006

George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. Journal of controlled release. 2006 Aug 10;114(1):1-4.

Lee KY, Mooney DJ. Alginate: properties and biomedical applications. Progress in polymer science. 2012 Jan 1;37(1):106-26.

Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterials. 2000 Dec 1;21(23):2335-46.

Rowe RC, Sheskey PJ, Quinn ME, editors. Handbook of pharmaceutical excipients. London: Pharmaceutical press; 2006 Jan 30.

Crowley MM, Zhang F, Repka MA, Thumma S, Upadhye SB, Kumar Battu S, McGinity JW, Martin C. Pharmaceutical applications of hot-melt extrusion: part I. Drug development and industrial pharmacy. 2007 Jan 1;33(9):909-26.

Aulton ME, Taylor K, editors. Aulton's pharmaceutics: the design and manufacture of medicines. Elsevier Health Sciences; 2013.

Sharma M, Dev SK, Kumar M, Shukla AK. Microspheres as suitable drug carrier in sustained release drug delivery: an overview. Asian Journal of Pharmacy And Pharmacology. 2018;4(2):102-8.

Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Biointerfaces. 2010;75(1):1–18. https://doi.org/10.1016/j.colsurfb.2009.09.001

Vehring R. Pharmaceutical particle engineering via spray drying. Pharmaceutical research. 2008 May;25(5):999-1022.

Feng T, Zhang Y, Huang Y, et al. Spray drying in pharmaceutical applications: Recent advances and challenges. Advanced Powder Technology. 2021;32(1):1–15.

Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan-based microspheres in drug delivery. International Journal of Biological Macromolecules. 2021;167:1041–1056.

Jyothi NVN, Prasanna PM, Sakarkar SN, et al. Microencapsulation techniques, factors influencing encapsulation efficiency. International Journal of Pharmaceutical Sciences Review and Research. 2010;3(2):509–531.

Singh MN, Hemant KSY, Ram M, Shivakumar HG. Microencapsulation: A promising technique for controlled drug delivery. Journal of Microencapsulation. 2010;27(2):187–197.

Whitesides GM. The origins and the future of microfluidics. nature. 2006 Jul 27;442(7101):368-73.

Shang L, Cheng Y, Zhao Y.Emerging droplet microfluidics. Chemical Reviews. 2017;117(12):7964–8040. https://doi.org/10.1021/acs.chemrev.6b00848

Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. The AAPS journal. 2014 Jul;16(4):771-83.

ICH Q8(R2). Pharmaceutical Development. 2009.

Goycoolea FM, et al. Chitosan-based polyelectrolyte complexes: Formation and applications in drug delivery. International Journal of Pharmaceutics. 2011;403(1–2):1–15. https://doi.org/10.1016/j.ijpharm.2010.10.029

Xie J, Jiang J, Davoodi P, Srinivasan MP, Wang CH. Electrospray fabrication of polymeric microparticles and nanoparticles for drug delivery. Acta Biomaterialia. 2015;19:29–51. https://doi.org/10.1016/j.actbio.2015.02.036

Kankala RK, Zhang YS, Wang SB, Lee CH, Chen AZ. Supercritical fluid technology: An emerging approach for drug delivery and biomedical applications. Advanced Drug Delivery Reviews. 2020;156:29–47. https://doi.org/10.1016/j.addr.2020.01.001

Danaei MR, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari YM. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018 May 18;10(2):57.

Galande P, Yadav V, Borkar S. A review on microspheres: preparation, characterization and applications. Asian Journal of Pharmaceutical Research and Development. 2022 Dec 14;10(6):128-33.

Dhadde Gurunath S, Mali Hanmant S, Raut Indrayani D, Nitalikar Manoj M, Bhutkar Mangesh A. A review on microspheres: types, method of preparation, characterization and application. Asian Journal of Pharmacy and Technology. 2021 Apr;11(2):149-55.

Gurung BD, Kakar S. An overview on microspheres. Int J Health Clin Res. 2020;3(1):11-24.

Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. Journal of pharmaceutical sciences. 1997 Jan;86(1):1-2.

Pavia DL, Lampman GM, Kriz GS, Vyvyan JR. Introduction to spectroscopy 4th edition. Cram 101 Learning system. 2012:15-85.

Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, Cho JM, Yun G, Lee J. Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian journal of pharmaceutical sciences. 2014 Dec 1;9(6):304-16.

ICH Q1A(R2). Stability Testing of New Drug Substances and Products. 2003.

Bruschi ML. Strategies to modify the drug release from pharmaceutical systems. Woodhead Publishing; 2025 Oct 1.

Siepmann J, Peppas NA. Higuchi equation: Derivation, applications, use and misuse. International journal of pharmaceutics. 2011 Oct 10;418(1):6-12.

Ding L, Agrawal P, Singh SK, Chhonker YS, Sun J, Murry DJ. Polymer-Based Drug Delivery Systems for Cancer Therapeutics. Polymers (Basel). 2024 Mar 19;16(6):843. doi: 10.3390/polym16060843. PMID: 38543448; PMCID: PMC10974363.

Jiang C, Kuang L, Merkel MP, Yue F, Cano-Vega MA, Narayanan N, Kuang S, Deng M. Biodegradable Polymeric Microsphere-Based Drug Delivery for Inductive Browning of Fat. Front Endocrinol (Lausanne). 2015 Nov 9;6:169. doi: 10.3389/fendo.2015.00169. PMID: 26617571; PMCID: PMC4639710.

Patel A, Cholkar K, Mitra AK. Recent developments in cardiovascular drug delivery systems. Eur J Pharm Biopharm. 2022;173:1–15.

Ventola CL. Progress in hormone delivery systems. P T. 2017;42(12):742–755.

Zhao L, Seth A, Wibowo N, Zhao CX, Mitter N, Yu C, et al. Nanoparticle vaccines. Adv Drug Deliv Rev. 2023;195:114812.

Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric nanoparticles for drug delivery to the central nervous system. J Control Release. 2021;329:285–305.

Yadav KS, Rajpurohit R, Sharma S. Advances in ocular drug delivery systems using biodegradable polymers. Drug Deliv Transl Res. 2022;12:1254–1272.

Sung JC, Pulliam BL, Edwards DA. Nanoparticles for drug delivery to the lungs. Adv Drug Deliv Rev. 2007;59(11):1143–1164.

Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive drug delivery systems: a review. AAPS PharmSciTech. 2011;12(2):584–598.

Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nature reviews Drug discovery. 2014 Sep;13(9):655-72.

Freiberg S, Zhu XX. Polymer microspheres for controlled drug release. International journal of pharmaceutics. 2004 Sep 10;282(1-2):1-8.

Ventola CL. The nanomedicine revolution: part 1: emerging concepts. Pharmacy and Therapeutics. 2012 Sep;37(9):512.

Dash SK, Khan AS, Das SR, Padhan A, Rout D, Behera BC. Formulation and in-vitro evaluation of sustained released glibenclamide microspheres. International Journal of Pharmaceutical Sciences and Research. 2012 May 1;3(5):1433.

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Published

2026-04-15

How to Cite

Tusara Kanta Behera, Santosh Kumar Dash, Jyotirmaya Parida, Khagesh Bhoi, Lokesh Kumar Barik, Madhusudan Behera, … Kundan Bishi. (2026). Sustained Release Microspheres in Drug Delivery: Formulation Strategies, Characterization, and Therapeutic Application. Asian Journal of Pharmaceutical Research and Development, 14(2), 163–173. https://doi.org/10.22270/ajprd.v14i2.1736