MODIFIED RELEASE MULTI-UNIT SYSTEM: A REVIEW
DOI:
https://doi.org/10.22159/ijcpr.2025v17i6.7062Keywords:
Modified release, Multiunit dosage form, Pelletization, Extrusion–spheronization, Drug delivery systems, Controlled release, Sustained release, Multiparticulates, Formulation development, Pharmaceutical pelletsAbstract
Modified release multiunit dosage forms (MUFs) have emerged as a promising approach to achieve controlled and site-specific drug delivery with improved therapeutic outcomes. Pelletization, particularly via extrusion–spheronization, offers numerous formulation advantages, including uniform size, excellent flowability, and enhanced drug release control. This review provides a comprehensive overview of pelletization techniques with an emphasis on extrusion–spheronization, detailing its critical process parameters, formulation variables, and evaluation methods. Additionally, the classification of modified release systems and the comparative advantages of MUFs over single-unit systems are discussed. The integration of these technologies supports the development of patient-centric and robust drug delivery platforms with greater safety, efficacy, and compliance.
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References
1. Rahman MA, Ahuja A, Baboota S, Bhavna, Bali V, Saigal N. Recent advances in pelletization technique for oral drug delivery: a review. Curr Drug Deliv. 2009;6(1):122-9. doi: 10.2174/156720109787048339, PMID 19418964.
2. Vaphare AM, Banerjee SK, Gadhave MV, Gaikwad DD. Pelletization techniques: a review. Asian J Pharm Res Dev. 2014;2(3):103-14.
3. Deb R, Ahmed AB. Pellets and pelletization techniques: a critical review. Int Res J Pharm. 2016;4(4):90-5. doi: 10.7897/2230-8407.04414.
4. Punia S, Bala R, Rana AC. Pelletization techniques: a literature review. Int Res J Pharm. 2012;3(3):30-4.
5. Begum AR, Ganesh NS, Chandy V. A study on different pellet formation techniques and its evaluation parameters a review. Int J Curr Pharm Sci. 2019;11(2):7-13. doi: 10.22159/ijcpr.2019v11i2.33020.
6. Kammili L, Senthil V, Rathi V. Pelletization technology: a quick review. Int J Pharm Sci Res. 2011;2(6):1337-55. doi: 10.13040/IJPSR.0975 8232.2(6).1337 55.
7. Sharma A, Chaurasia S. Multiparticulate drug delivery system: pelletization through extrusion and spheronization. Int Res J Pharm. 2013;4(2):137-40.
8. Trivedi NR, Rajan MG, Johnson JR, Shukla AJ. Pharmaceutical approaches to preparing pelletized dosage forms using the extrusion spheronization process. Crit Rev Ther Drug Carrier Syst. 2007;24(1):1-40. doi: 10.1615/critrevtherdrugcarriersyst.v24.i1.10, PMID 17430098.
9. Sarkar S, Heng PW, Liew CV. Insights into the functionality of pelletization aid in pelletization by extrusion spheronization. Pharm Dev Technol. 2013;18(1):61-72. doi: 10.3109/10837450.2011.621210, PMID 21981607.
10. Koo OM, Heng PW. The influence of microcrystalline cellulose grade on shape and shape distributions of pellets produced by extrusion spheronization. Chem Pharm Bull (Tokyo). 2001;49(11):1383-7. doi: 10.1248/cpb.49.1383, PMID 11724226.
11. Petrovick GF, Pein M, Thommes M, Breitkreutz J. Spheronization of solid lipid extrudates: a novel approach on controlling critical process parameters. Eur J Pharm Biopharm. 2015;92:15-21. doi: 10.1016/j.ejpb.2015.02.004, PMID 25681745.
12. Dukic Ott A, Thommes M, Remon JP, Kleinebudde P, Vervaet C. Production of pellets via extrusion spheronisation without the incorporation of microcrystalline cellulose: a critical review. Eur J Pharm Biopharm. 2009;71(1):38-46. doi: 10.1016/j.ejpb.2008.08.005, PMID 18771727.
13. Dukic Ott A, De Beer T, Remon JP, Baeyens W, Foreman P, Vervaet C. In vitro and in vivo evaluation of enteric coated starch based pellets prepared via extrusion/spheronisation. Eur J Pharm Biopharm. 2008;70(1):302-12. doi: 10.1016/j.ejpb.2008.04.019, PMID 18579353.
14. Anisha Gulhane, Bhoyar BB. A review on multi-unit particulate system: advanced technology for novel drug delivery system. Int J Pharm Sci. 2025;3(6):780-9. doi: 10.5281/zenodo.15597547.
15. Sinha VR, Agrawal MK, Kumria R. Influence of formulation and excipient variables on the pellet properties prepared by extrusion spheronization. Curr Drug Deliv. 2005;2(1):1-8. doi: 10.2174/1567201052772898, PMID 16305403.
16. Koo OM, Heng PW. The influence of MCC grade on extrusion spheronization outcomes. Chem Pharm Bull PMC. 2001;49(11):1383-7. doi: 10.1248/cpb.49.1383.
17. Khan A, Malviya R, Sharma PK. Multi-unit drug delivery system: a brief review of pelletization technique. World Appl Sci J. 2014;31(3):2137-40. doi: 10.5829/idosi.wasj.2014.31.12.8498.
18. Petrovick GF, Thommes M. Quality aspects in the development of pelletized dosage forms. Eur J Pharm Biopharm. 2022;182:113-27. doi: 10.1016/j.ejpb.2022.05.012.
19. Rahman MA, Ahuja A, Baboota S, Bhavna, Bali V, Saigal N. Recent advances in pelletization technique for oral drug delivery: a review. Curr Drug Deliv. 2009;6(1):122-9. doi: 10.2174/156720109787048339, PMID 19418964.
20. Muley S, Nandgude T, Poddar S. Extrusion spheronization a promising pelletization technique: in-depth review. Asian J Pharm Sci. 2016;11(6):684-99. doi: 10.1016/j.ajps.2016.08.001.
21. Shah RD, Kabadi M, Pope DG, Augsburger LL. Physicomechanical characterization of the extrusion spheronization process. I. Instrumentation of the extruder. Pharm Res. 1994;11(3):355-60. doi: 10.1023/a:1018996500749, PMID 8008698.
22. Sinha VR, Agrawal MK, Kumria R, Bhinge JR. Influence of operational variables on properties of piroxicam pellets prepared by extrusion spheronization: a technical note. AAPS PharmSciTech. 2007;8(1):E137–E41. doi: 10.1208/pt0801020, PMID 17408219.
23. Koo OM, Heng PW. The influence of microcrystalline cellulose grade on shape and shape distributions of pellets produced by extrusion spheronization. Chem Pharm Bull (Tokyo). 2001;49(11):1383-7. doi: 10.1248/cpb.49.1383, PMID 11724226.
24. Arshad MS, Zafar S, Yousef B, Alyassin Y, Ali R, AlAsiri A. A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing. Adv Drug Deliv Rev. 2021;175:113840. doi: 10.1016/j.addr.2021.113840.
25. PaLkowski L, Karolak M, Kubiak B, Blaszczynski J, Slowinski R, Thommes M. Optimization of pellets manufacturing process using rough set theory. Eur J Pharm Sci. 2018;124:295-303. doi: 10.1016/j.ejps.2018.08.027, PMID 30157461.
26. Abdul S, Chandewar AV, Jaiswal SB. A flexible technology for modified-release drugs: multiple-unit pellet system (MUPS). J Control Release. 2010;147(1):2-16. doi: 10.1016/j.jconrel.2010.05.014, PMID 20493217.
27. Wang J, Kan S, Chen T, Liu J. Application of quality by design (QbD) to formulation and processing of naproxen pellets by extrusion spheronization. Pharm Dev Technol. 2015;20(2):246-56. doi: 10.3109/10837450.2014.908300, PMID 25069591.
28. De Barros JM, Lechner T, Charalampopoulos D, Khutoryanskiy VV, Edwards AD. Enteric-coated spheres produced by extrusion/spheronization provide effective gastric protection and efficient release of live therapeutic bacteria. Int J Pharm. 2015;493(1-2):483-94. doi: 10.1016/j.ijpharm.2015.06.051, PMID 26188314.
29. Dukic Ott A, Thommes M, Remon JP, Kleinebudde P, Vervaet C. Production of pellets via extrusion spheronisation without the incorporation of microcrystalline cellulose: a critical review. Eur J Pharm Biopharm. 2009;71(1):38-46. doi: 10.1016/j.ejpb.2008.08.005, PMID 18771727.
30. Khadam VK, Chawra HS, Singh RP. Extrusion spheronization, pelletization technique and Wurster coating (bottom spray): a review. Future J Pharm Health Sci. 2023;3(3):263-76. doi: 10.26452/fjphs.v3i3.474.
31. McConnell EL, Basit AW. Modified release oral drug delivery. In: Aulton ME, Taylor KM, editors. Aulton’s pharmaceutics: the design and manufacture of medicines. 5th ed. Amsterdam: Elsevier; 2018. p. 564-79.
32. Al Hashimi N, Begg N, Alany RG, Hassanin H, Elshaer A. Oral modified release multiple unit particulate systems: compressed pellets, microparticles and nanoparticles. Pharmaceutics. 2018 Oct 4;10(4):176. doi: 10.3390/pharmaceutics10040176, PMID 30287798, PMCID PMC6321440.
33. Foppoli A, Cerea M, Palugan L, Zema L, Melocchi A, Maroni A. Evaluation of powder layering vs. spray coating techniques in the manufacturing of a swellable/erodible pulsatile delivery system. Drug Dev Ind Pharm. 2020;46(8):1230-7. doi: 10.1080/03639045.2020.1788060, PMID 32597251.
34. Agrawal S, Fernandes J, Shaikh F, Patel V. Quality aspects in the development of pelletized dosage forms. Heliyon. 2022;8(2):e08956. doi: 10.1016/j.heliyon.2022.e08956, PMID 35243077.
35. Sosnik A, Augustine R. Challenges in oral drug delivery of antiretrovirals and the innovative strategies to overcome them. Adv Drug Deliv Rev. 2016;103:105-20. doi: 10.1016/j.addr.2015.12.022, PMID 26772138.
36. Roy P, Shahiwala A. Multiparticulate formulation approach to pulsatile drug delivery: current perspectives. J Control Release. 2009;134(2):74-80. doi: 10.1016/j.jconrel.2008.11.011, PMID 19105973.
37. Waghmare SM, More NN, Jagtap SR, Mandhare TA, Soni GK, Kale AY. Techniques and evaluation tests for colon cancer treatment using pellets: a review. Curr Res Pharm Sci. 2024;13(4):157-66. doi: 10.24092/CRPS.2023.130401.
38. Arora S, Rathore C. Formulation and in vitro evaluation of polymer-based extended release pellet tablets of diltiazem. Int J Life Sci Pharma Res. 2023;13(6):299–309. doi: 10.22376/ijlpr.2023.13.6.
39. Rahman MA, Ahuja A, Baboota S, Bhavna, Bali V, Saigal N. Recent advances in pelletization technique for oral drug delivery: a review. Curr Drug Deliv. 2009;6(1):122-9. doi: 10.2174/156720109787048339, PMID 19418964.
40. Kan S, Lu J, Liu J, Wang J, Zhao Y. A Quality by design (QbD) case study on enteric-coated pellets: screening of critical variables and establishment of design space at laboratory scale. Asian J Pharm Sci. 2014;9(5):268-78. doi: 10.1016/j.ajps.2014.07.005.
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