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image of Identifying Optimized Parameters to Enhance the Productivity of Gas Generating Pellets Using a Dome Type Extruder

Abstract

Introduction

The extrusion-spheronization process continues to be utilized in pharmaceutical manufacturing, as evidenced by several recent patents and articles. The primary challenge in pelletization extrusion spheronization is optimizing the production process to achieve high yields of spherical pellets while keeping production costs low. Therefore, this study aimed to identify the ideal parameters for maximizing production rates using a dome extruder while maintaining the desired physical characteristics of the pellets.

Methods

The pellet formulation comprised apixaban, microcrystalline cellulose, hypromellose, and sodium bicarbonate. The study employed the face-centered central design to assess the impact of various process variables. Key factors included extruder speed, spheronization speed, and spheronization time, which were determined based on the preliminary analyses. Characterization of pellets encompassed measurements of sphericity aspect ratio, friability, bulk density, and percentage yield.

Results

The optimized parameters for extrusion speed spanned from 23 to 27 rpm, while spheronization speed extended from 700 to 900 rpm at 5 min to 7 min of spheronization time, yielding more than 90% of the desired fraction of spherical pellets with good physical properties.

Discussion

It was discerned that extrusion and spheronization speed emerged as critical process parameters within a defined spheronization time for maximizing production rates while concurrently maintaining satisfactory pellet properties.

Conclusion

This study successfully optimized process parameters for pellet production using a dome-type extruder by employing a Quality by Design (QbD) approach. Key factors influencing pellet yield and quality, such as extrusion speed, spheronization speed, and time, were identified and systematically optimized.

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2025-05-08
2025-09-28

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References

  1. Häring A. Vetchý D. Janovská L. Krejčová K. Rabišková M. Differences in characteristics of pellets prepared by different pelletization methods. Drug Dev. Ind. Pharm. 2008 34 3 289 296 10.1080/03639040701655960 18363144
    [Google Scholar]
  2. Bryan M.P. Atherton L.N. Duffield S. Stages in spheronisation: Evolution of pellet size and shape during spheronisation of microcrystalline cellulose-based paste extrudates. Powder Technol. 2015 270 Part A 163 175 10.1016/j.powtec.2014.10.014
    [Google Scholar]
  3. Désiré A. Paillard B. Bougaret J. A comparison of three extrusion systems (Part I): The influence of water content and extrusion speed on pellet properties. Pharm. Technol. 2011 2011 56 65
    [Google Scholar]
  4. Muley S. Nandgude T. Poddar S. Extrusion–spheronization a promising pelletization technique: In-depth review. Asian J. Pharmaceut. Sci. 2016 11 6 684 699 10.1016/j.ajps.2016.08.001
    [Google Scholar]
  5. 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 2 246 256 10.3109/10837450.2014.908300 25069591
    [Google Scholar]
  6. Raviteja G.V. Panner Selvam R. Chandy V. Extrusion spheronization and the recent advancements in pellets. Human J. 2022 24 1 1 19
    [Google Scholar]
  7. Weert X. Lawrence C.J. Adams M.J. Screw extrusion of food powders: prediction and performance. Chem. Engin. Sci. 2001 56 5 1933 1949 10.1016/S0009‑2509(00)00463‑2
    [Google Scholar]
  8. Engländer A. Burbidge A. Blackburn S. A preliminary evaluation of single screw paste extrusion. Chem. Eng. Res. Des. 2000 78 5 790 794 10.1205/026387600527815
    [Google Scholar]
  9. Botten A.J. Burbidge A.S. Blackburn S. A model to predict the pressure development in single screw extrusion. J. Mater. Process. Technol. 2003 135 2-3 284 290 10.1016/S0924‑0136(02)00859‑2
    [Google Scholar]
  10. Zhang M. Li Y. Spheronisation of a basket screen-extruded paste using screens of different hole diameters. Powder Technol. 2016 299 199 209 10.1016/j.powtec.2016.05.038
    [Google Scholar]
  11. Fielden K.E. Newton J.M. Rowe R.C. The influence of lactose particle size on spheronization of extrudate processed by a ram extruder. Int. J. Pharmaceut. 1992 81 2-3 205 224 10.1016/0378‑5173(92)90013‑R
    [Google Scholar]
  12. Fielden K.E. Newton J.M. Rowe R.C. 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 2-3 225 233 10.1016/0378‑5173(92)90014‑S
    [Google Scholar]
  13. Zhang M. Rough S.L. Ward R. Seiler C. Wilson D.I. A comparison of ram extrusion by single-holed and multi-holed dies for extrusion-spheronisation of microcrystalline-based pastes. Int. J. Pharm. 2011 416 1 210 222 10.1016/j.ijpharm.2011.05.037 21742021
    [Google Scholar]
  14. Rabišková M. Weingartová D. Häring A. The influence of the extrusion die on pellet characteristics. Ceska Slov. Farm. 2007 56 1 17 20
    [Google Scholar]
  15. Hileman G.A. Goskonda S.R. Spalitto A.J. Upadrashta S.M. Response surface optimization of high dose pellets by extrusion and spheronization. Int. J. Pharm. 1993 100 1-3 71 79 10.1016/0378‑5173(93)90077‑S
    [Google Scholar]
  16. Lutchman D. Dangor C.M. Perumal D. Formulation of rate-modulating pellets for the release of ibuprofen: An extrusion–spheronization process. J. Microencapsul. 2005 22 6 643 659 10.1080/02652040500162535 16401580
    [Google Scholar]
  17. Galland S. Ruiz T. Delalonde M. Hydro-textural characterisation of wet granular media shaped by extrusion/spheronisation. Powder Technol. 2009 190 1-2 48 52 10.1016/j.powtec.2008.04.056
    [Google Scholar]
  18. Michie H. Podczeck F. Newton J.M. The influence of plate design on the properties of pellets produced by extrusion and spheronization. Int. J. Pharm. 2012 434 1-2 175 182 10.1016/j.ijpharm.2012.05.050 22659150
    [Google Scholar]
  19. Sousa J.J. Sousa A. Podczeck F. Newton J.M. Factors influencing the physical characteristics of pellets obtained by extrusion-spheronization. Int. J. Pharm. 2002 232 1-2 91 106 10.1016/S0378‑5173(01)00908‑5 11790493
    [Google Scholar]
  20. El-Mahdi I.M. El-Shhibia S.A. Effect of spheronizer plate design on the spheronization of ketoprofen. Fut. J. Pharmaceut. Sci. 2017 3 2 153 157 10.1016/j.fjps.2017.05.004
    [Google Scholar]
  21. Evers M. Weis D. Antonyuk S. Thommes M. Scale-up of the rounding process in pelletization by extrusion-spheronization. Pharm. Dev. Technol. 2019 24 8 1014 1020 10.1080/10837450.2019.1621900 31232624
    [Google Scholar]
  22. Désiré A. Paillard B. Bougaret J. A comparison of three extrusion systems (Part II). Pharm. Technol. 2011 35 6 56 61
    [Google Scholar]
  23. Patel R. Mehta D. A gastroretentive composition comprising apixaban. Patent WO 2024261686 A1, 2024.
  24. Pertile M. Cerea M. Foppoli A. Pharmaceutical Dosage Forms For Pulsatile Release. Patent WO 2024/240775 A1, 2024.
  25. Varum F. Decollogny S. Bravo R. Method for preparing a solid dosage form comprising antibodies by wet granulation. Patent EP 3459527 A1, 2019.
  26. Drott J. Nicklasson F. Horler A. Composition and method for pretreating cancer. Patent EP 4483864A1, 2025.
  27. Vishal D. Multiparticulate drug delivery of losartan potassium via extrusion-spheronization: Formulation and dissolution comparisons. BIOI 2024 5 1 0079 10.15212/bioi‑2024‑0079
    [Google Scholar]
  28. Patel R. Trivedi H. Patel H. Formulation and optimization of pellets containing zaltoprofen by extrusion spheronization technique. J. Pharm. Sci. 2024 11 1 11 32 37898164
    [Google Scholar]
  29. da Silva J.B. dos Santos R.S. Vecchi C.F. Bruschi M.L. Drug delivery platforms containing thermoresponsive polymers and mucoadhesive cellulose derivatives: A review of patents. Rec. Adv. Drug Deliv. Formulat. 2022 16 2 90 102 10.2174/2667387816666220404123625 35379163
    [Google Scholar]
  30. Jadhav N. Irny P. Mokashi A. Souche P. Paradkar A. Pelletization by extrusion spheronization technique: An excipient review. Drug Deliv. Lett. 2012 2 2 132 145 10.2174/2210303111202020132
    [Google Scholar]
  31. Siebel F. Kleinebudde P. Croscarmellose sodium as pelletization aid in extrusion-spheronization. AAPS PharmSciTech 2024 25 6 147 10.1208/s12249‑024‑02864‑0 38937406
    [Google Scholar]
  32. Purandare S. Khot S. Avachat A. Fabrication of pellets via extrusion-spheronization for engineered delivery of Famotidine through specialized straws for Paediatrics. Ann. Pharm. Fr. 2024 82 2 271 284 10.1016/j.pharma.2023.12.008 38135035
    [Google Scholar]
  33. Patel H. Kaur K. Ranch K. Formulation and evaluation of co-processed MCCCore pellets and confirm its application in layering of drugs with different solubility. J. Pharm. Appl. Sci. 2016 3 1 1 10
    [Google Scholar]
  34. Garekani H.A. Nokhodchi A. Rayeni M.A. Sadeghi F. Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration. Drug Dev. Ind. Pharm. 2013 39 8 1238 1246 10.3109/03639045.2012.707207 22873946
    [Google Scholar]
  35. ICH Q8 (R2) Pharmaceutical development - Scientific guideline. 2009 Available from:https://www.ema.europa.eu/en/ich-q8-r2-pharmaceutical-development-scientific-guideline (accessed on 17-3-2024).
  36. ICH guideline Q9 on quality risk management. 2005 Available from:https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-guideline-q9-quality-risk-management-step-5-first-version_en.pdf (accessed on 17-3-2024).
  37. 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. Pharmaceut. Sci. 2014 9 5 268 278 10.1016/j.ajps.2014.07.005
    [Google Scholar]
  38. Rana H.B. Gohel M.C. Dholakia M.S. Gandhi T.R. Omri A. Thakkar V.T. Development of sustained release pellets of galantamine HBr by extrusion spheronization technique incorporating risk based QbD approach. Res. J. Pharm. Technol. 2018 11 11 4899 4910 10.5958/0974‑360X.2018.00892.2
    [Google Scholar]
  39. Shah H.P. Prajapati S.T. Patel C.N. Quality by Design enabled development and optimization of gastroretentive floating matrix tablets of dipyridamole. Asian J. Pharm. 2017 11 2
    [Google Scholar]
  40. Mahapatra A.P.K. Saraswat R. Botre M. Paul B. Prasad N. Application of response surface methodology (RSM) in statistical optimization and pharmaceutical characterization of a patient compliance effervescent tablet formulation of an antiepileptic drug levetiracetam. Fut. J. Pharmaceut. Sci. 2020 6 1 82 10.1186/s43094‑020‑00096‑0
    [Google Scholar]
  41. Dasankoppa F.S. N Sholapur H. Byahatti A. Abbas Z. Komal S K. Subrata K. Application of response surface optimization methodology in designing orodispersible tablets of antidiabetic drug. J. Young Pharm. 2020 12 2 173 177 10.5530/jyp.2020.12.35
    [Google Scholar]
  42. Kuchukuntla M. Palanivel V. Madhubabu A. Tofacitinib citrate-loaded nanoparticle gel for the treatment of alopecia areata: Response surface design, formulation, and in vitro-in vivo characterization. Rec. Adv. Drug Deliv. Formulat. 2023 17 4 314 331 10.2174/0126673878264814231106094853 38031780
    [Google Scholar]
  43. Pai R.S. Singh G. Devi V.K. Response surface methodology and process optimization of sustained release pellets using Taguchi orthogonal array design and central composite design. J. Adv. Pharm. Technol. Res. 2012 3 1 30 40 10.4103/2231‑4040.93565 22470891
    [Google Scholar]
  44. Sánchez-Lafuente C. Furlanetto S. Fernández-Arévalo M. Alvarez-Fuentes J. Rabasco A.M. Faucci M.T. Pinzauti S. Mura P. Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design. Int. J. Pharm. 2002 237 1-2 107 118 10.1016/S0378‑5173(02)00028‑5 11955809
    [Google Scholar]
  45. Krogars K. Heinämäki J. Vesalahti J. Marvola M. Antikainen O. Yliruusi J. Extrusion–spheronization of pH-sensitive polymeric matrix pellets for possible colonic drug delivery. Int. J. Pharm. 2000 199 2 187 194 10.1016/S0378‑5173(00)00382‑3 10802412
    [Google Scholar]
  46. Mehta D. Parejiya P. Barot B. Suthar D. Shelat P. Polyethylene oxide-based pH-independent drug delivery system: Formulation and optimization by central composite design. Drug Deliv. Lett. 2013 3 3 220 232 10.2174/22103031113039990007
    [Google Scholar]
  47. Sántha K. Kállai-Szabó N. Fülöp V. Jakab G. Gordon P. Kállai-Szabó B. Balogh E. Antal I. Comparative evaluation of pellet cushioning agents by various imaging techniques and dissolution studies. AAPS PharmSciTech 2021 22 1 14 10.1208/s12249‑020‑01902‑x 33377174
    [Google Scholar]
  48. Saripella K.K. Loka N.C. Mallipeddi R. Rane A.M. Neau S.H. 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 2 368 379 10.1208/s12249‑015‑0345‑6 26169900
    [Google Scholar]
  49. Kheni P. Mehta D. A QbD assisted modified release formulation of Midodrine Hydrochloride for management of long-term hypotension. Int. J. Pharm. Sci. Drug Res. 2021 13 5 524 535 10.25004/IJPSDR.2021.130510
    [Google Scholar]
  50. Podczeck F. Rahman S.R. Newton J.M. Evaluation of a standardized procedure to assess the shape of pellets using image analysis. Int. J. Pharm. 1999 1999 192
    [Google Scholar]
  51. Niharika M.G. Krishnamoorthy K. Akkala M. Overview on floating drug delivery system. Int. J. Appl. Pharmaceut. 2018 10 6 65 71 10.22159/ijap.2018v10i6.28274
    [Google Scholar]
  52. Pharmaceutical Quality System Q10. 2008 Available from:https://database.ich.org/sites/default/files/Q10%20Guideline.pdf (accessed on 17-3-2024).
/content/journals/raddf/10.2174/0126673878351312250502072134
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Identifying Optimized Parameters to Enhance the Productivity of Gas Generating Pellets Using a Dome Type Extruder
Bentham Science Publishers ; https://doi.org/10.2174/0126673878351312250502072134
/content/journals/raddf/10.2174/0126673878351312250502072134
/content/journals/raddf/10.2174/0126673878351312250502072134
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  • Article Type:     Research Article
Keywords: floating pellets ; Extrusion spheronization ; yield enhancement ; response surface methodology ; dome extruder ; optimization by DoE

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