AN OUTLINE OF VARIABLES IN PELLETIZATION BY EXTRUSION AND SPHERONIZATION

  • RAKESH V. MISHRA Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India
  • SHUBHAM G. PALDEWAR Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India
  • TANAJI D. NANDGUDE Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India

Abstract

Pelletization is an agglomeration process which converts fine granules or powders of bulk drugs into small, free-flowing, spherical units, known as pellets. The pelletization can be achieved either through agitation, compaction (extrusion-spheronization), drug layering and globulation. Among the various pelletization techniques extrusion–spheronization process is preferred over other methods for the preparation of pellets as it allows the incorporation of the higher amount of drug, modified physical characteristics of the drug (density, sphericity, narrow size distribution, smoother surface) and multiple drugs can be easily combined in the same unit. This current review summarizes the findings or investigations by the researchers on various variables, including process parameters, equipment parameters and formulation parameters influencing the quality of pellets. The article also focuses on process optimization and additives used in pellets formulation. To prepare the current review search criterion used was the parameters affecting final pellet characterization in the extrusion spheronization process. The sources were peer-reviewed relevant scientific articles of recognized journals. Keywords used as filters were extrusion, spheronization, formulation parameters, process parameters, equipment parameters, moisture content, granulating liquid, drying rate, extrusion temperature, spheronizer load, pelletization. Literature survey has been done in a range of years (1992-2019) regarding the various variables of the extrusion spheronization process, which affects and has foremost impact on the final quality of pellets so as to make the review updated and comprehensive.

Keywords: Pelletization, Extrusion, Spheronization, Pellets, Process parameter and Formulation parameter

Author Biography

RAKESH V. MISHRA, Department of Pharmaceutics, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411018, Maharashtra, India

Asst. Prof. (Department of Pharmaceutics)

References

1. Muley S, Nandgude T, Poddar S. Extrusion–spheronization a promising pelletization technique: In-depth review. Asian J Pharm Sci 2016;11:684–99.
2. Nandgude TD, Hasabe PS. Formulation and development modified-release apremilast pellets. Asian J Pharm 2018;12:1228–35.
3. Vervaet C, Baert L, Remon JP. Extrusion-spheronisation a literature review. Int J Pharm 1995;116:131–46.
4. Lvanya K. Pelletization technology: a quick review. Int J Pharm 2011;2:1337–55.
5. Patil SM, Mishra RV, Shirolkar SV. Development and evaluation of sustain release simvastatin pellets. Res J Pharm Technol 2017;10:2467–73.
6. Mishra RV, Dhole SN. Multiparticulate floating drug delivery system of anagliptin: design and optimization for its efficacy in the management of the metabolic syndrome. Int J Appl Pharm 2019;11:171–81.
7. Bahekar J, Wadher S. Formulation development of colon targeted mesalamine pellets: in vitro-in vivo release study. Int J Appl Pharm 2019;11:125-32.
8. Mesiha MS, Valltes J. A screening study of lubricants in wet powder masses suitable for extrusion-spheronization. Drug Dev Ind Pharm 1993;19:943–59.
9. Fielden KE, Newton JM, Obrien P, Rowe RC. Thermal studies on the interaction of water and microcrystalline cellulose. Eur J Pharm Sci 1988;674–8. https://doi.org/10.1111/j.2042-7158.1988.tb06993.x
10. Mishra R, Suradkar P, Nandgude T. Statistical design and optimization of ketorolac tromethamine gastroretentive multiparticulate delivery system. Int J Res Pharm Sci 2019;10:2399–408.
11. Thiry J, Krier F, Evrard B. A review of pharmaceutical extrusion: critical process parameters and scaling-up. Int J Pharm 2015;479:227–40.
12. Sinha VR, Agrawal MK, Agarwal A, Singh G, Ghai D. Extrusion-spheronization: process variables and characterization. Crit Rev Ther Drug Carrier Syst 2009;26:275–331.
13. Dyer AM, Khan KA, Aulton ME. Effect of the drying method on the mechanical and drug release properties of pellets prepared by extrusion-spheronization. Drug Dev Ind Pharm 1994;20:3045–68.
14. Berggren J, Alderborn G. Drying behaviour of two sets of microcrystalline cellulose pellets. Int J Pharm 2001;219:113–26.
15. Bashaiwoldu AB, Podczeck F, Newton JM. A study on the effect of drying techniques on the mechanical properties of pellets and compacted pellets. Eur J Pharm Sci 2004;21:119–29.
16. Murray T, Rough SL, Wilson DI. The effect of drying technique on tablets formed from extrusion-spheronization granules. Chem Eng Res Des 2007;85:996–1004.
17. Newton JM, Chapman SR, Rowe RC. The influence of process variables on the preparation and properties of spherical granules by the process of extrusion and spheronisation. Int J Pharm 1995;120:101–9.
18. Chariot M, Frances J, Lewis GA, Mathieu D, Luu RPT, Stevens HNE. A factorial approach to process variables of extrusion-spheronisation of wet powder masses. Drug Dev Ind Pharm 1987;13:1639–49.
19. Malinowski HJ, Smith WE. Use of factorial design to evaluate granulations prepared by spheronization. J Pharm Sci 1975;64:1688–92.
20. Saripella KK, Loka NC, Mallipeddi R, Rane AM, Neau SH. A quality by experimental design approach to assess the effect of formulation and process variables on the extrusion and spheronization of drug-loaded pellets containing polyplasdone® XL-10. AAPS PharmSciTech 2016;17:368–79.
21. Bolcskei E, Regdon G, Sovany T, Kleinebudde P, Pintye-Hodi K. Optimization of preparation of matrix pellets containing Eudragit ® NE 30D. Chem Eng Res Des 2012;90:651–7.
22. Wan LSC, Heng PWS, Liew CV. Spheronization conditions on spheroid shape and size. Int J Pharm 1993;96:59–65.
23. Ronowicz J, Thommes M, Kleinebudde P, Krysi?ski J. A data mining approach to optimize pellets manufacturing process based on a decision tree algorithm. Eur J Pharm Sci 2015;73:44–8.
24. Vervaet C, Baert L, Risha PA, Remon JP. The influence of the extrusion screen on pellet quality using an instrumented basket extruder. Int J Pharm 1994;7:29–39.
25. Sonaglio D, Bataille B, Ortigosa C, Jacob M. Factorial design in the feasibility of producing microcel MC 101 pellets by extrusion/spheronization. Int J Pharm 1995;115:53–60.
26. Zhang M, Mascia S, Rough SL, Ward R, Seiler C, Wilson DI. A novel lab-scale screen extruder for studying extrusion-spheronisation. Int J Pharm 2013;455:285–97.
27. Sonaglio D, Bataille B, Jacob M. Effect of extrusion and formulation parameters on the production of paracetamol–microcrystalline cellulose extrudates. Pharm Acta Helv 1997;72:69–74.
28. Zhang M, Wilson DI, Ward R, Seiler C, Rough SL. A comparison of screen and ram extrusion-spheronisation of simple pharmaceutical pastes based on microcrystalline cellulose. Int J Pharm 2013;456:489–98.
29. Lee KT, Ingram A, Rowson NA. Comparison of granule properties produced using twin screw extruder and high shear mixer: a step towards understanding the mechanism of twin screw wet granulation. Powder Technol 2013;238:91–8.
30. Bryan MP, Kent MD, Rickenbach J, Rimmer G, Wilson DI, Rough SL. The effect of mixing on the extrusion-spheronisation of a micro-crystalline cellulose paste. Int J Pharm 2015;479:1–10.
31. Michie H, Podczeck F, Newton JM. The influence of plate design on the properties of pellets produced by extrusion and spheronization. Int J Pharm 2012;434:175–82.
32. Zhang M, Li Y, Xing JF, Rough SL, Wilson DI. Influence of plate surface protuberance size and shape on the production of pellets by extrusion-spheronisation. Chem Eng Res Des 2016;109:97–107.
33. Kaffash E, Saremnejad F, Abbaspour M, Mohajeri SA, Garekani HA, Jafarian AH, et al. Statistical optimization of an alginate-based oral dosage form of 5-aminosalicylic acid aimed to colonic delivery: in vitro and in vivo evaluation. J Drug Delivery Sci Technol 2019;52:177–88.
34. Panigrahy RN, Panda SK, Veerareddy PR. Formulation and in vitro evaluation of combined floating-bioadhesive tablets of imatinib mesylate. Int J Pharm Pharm Sci 2017;9:27-33.
35. Hiremath SP, Makanapur C. Formulation and evaluation of orodispersible tablets of a model anti-hypertensive drug. Int J Pharm Pharm Sci 2017;9:34-8.
36. Dukic-Ott A, Remon JP, Foreman P, Vervaet C. Immediate release of poorly soluble drugs from starch-based pellets prepared via extrusion/spheronisation. Eur J Pharm Biopharm 2007;67:715–24.
37. Singh G, Pai RS, Kusum Devi V. Optimization of pellets containing solid dispersion prepared by extrusion/spheronization using central composite design and desirability function. J Young Pharm 2013;4:146–56.
38. Mummidi V, Rezwana S. The influence of HPC-L and eudragit L30 D-55 on delayed release omeprazole magnesium multiple-unit pellet system. Asian J Pharm Clin Res 2018;11:178–84.
39. Deshkar S, Satpute A. Formulation and optimization of curcumin solid dispersion pellets for improved solubility. Int J Appl Pharm 2020;12:36–46.
40. Fielden KE, Newton JM, Rowe RC. A comparison of the extrusion and spheronization behaviour of wet powder masses processed by a ram extruder and a cylinder extruder. Int J Pharm 1992;81:225–33.
41. Fielden KE, Newton JM, Rowe RC. Movement of liquids through powder beds. Int J Pharm 1992;7:47–60.
42. Luukkonen P, Newton JM, Podczeck F, Yliruusi J. Use of a capillary rheometer to evaluate the rheological properties of microcrystalline cellulose and silicified microcrystalline cellulose wet masses. Int J Pharm 2001;216:147–57.
43. 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;71:38–46.
44. Salve V, Mishra R, Nandgude T. Development and optimization of a floating multiparticulate drug delivery system for norfloxacin. Turkish J Pharm Sci 2019;16:326–34.
45. Levis SR, Deasy PB. Pharmaceutical applications of size reduced grades of surfactant co-processed microcrystalline cellulose. Int J Pharm 2001;230:25–33.
46. Mallipeddi R, Saripella KK, Neau SH. Use of fine particle ethylcellulose as the diluent in the production of pellets by extrusion-spheronization. Saudi Pharm J 2014;22:360–72.
47. Bolcskei E, Regdon G, Sovany T, Ghanam D, Knop K, Kleinebudde P, et al. Preparing of pellets by extrusion/spheronization using different types of equipment and process conditions. Drug Dev Ind Pharm 2014;40:762–4.
48. Lustig Gustafsson C, Kaur Johal H, Podczeck F, Newton JM. The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronisation. Eur J Pharm Sci 1999;8:147–52.
49. Tomer G. Water movement evaluation during extrusion of wet powder masses by collecting extrudate fractions. Int J Pharm 1999;182:71–7.
50. Stefan F, Henriksson G, Berghel J. Effects of moisture content during densification of biomass pellets, focusing on polysaccharide substances. Biomass Bioenergy 2019;122:322–30.
51. Dreu R, Sirca J, Pintye Hodi K, Burjan T, Planinsek O, Srcic S. Physicochemical properties of granulating liquids and their influence on microcrystalline cellulose pellets obtained by extrusion-spheronisation technology. Int J Pharm 2005;291:99–111.
52. Mascia S, Seiler C, Fitzpatrick S, Wilson DI. Extrusion-spheronisation of microcrystalline cellulose pastes using a non-aqueous liquid binder. Int J Pharm 2010;389:1–9.
53. Hamedelniel EI, Bajdik J, Sovany T, Kasa P, Pintye Hodi K. Effects of the wetting liquid and ethylcellulose on the properties of atenolol-containing pellets. J Drug Delivery Sci Technol 2011;21:195–200.
54. Gaith Z, Ali R, Dashevskiy A. Water-soluble and-insoluble polymers as binders for pellet preparation by extrusion/spheronization. J Drug Delivery Sci Technol 2019;49:1–5.
Statistics
72 Views | 85 Downloads
Citatons
How to Cite
MISHRA, R. V., PALDEWAR, S. G., & NANDGUDE, T. D. (2020). AN OUTLINE OF VARIABLES IN PELLETIZATION BY EXTRUSION AND SPHERONIZATION. International Journal of Applied Pharmaceutics, 12(4), 39-44. https://doi.org/10.22159/ijap.2020v12i4.37277
Section
Review Article(s)