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A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions

  • Research Article
  • Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability
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Abstract

Amorphous solid dispersions (ASDs) are a proven method of improving the solubility and bioavailability of poorly soluble compounds. Immediate release tablets are frequently used as final dosage form for ASDs. Increasing tableting process throughput during clinical development requires using larger, faster tablet presses which subject materials to higher strain rate. Many pharmaceutical materials show strain rate sensitivity, i.e., yield pressure sensitivity to compression speed. Currently, there is only scattered information available in scientific literature on how ASDs behave under different tablet compression speeds. The purpose of this study was to examine spray-dried ASDs’ sensitivity to strain rate under compression in a comprehensive study. We also investigated the drivers for such a strain sensitive behavior. A set of sample spray-dried powders, selected for their range of properties, were compressed using a simulated Korsch XL100 profile at 3 and 30 RPM and V-profile at 0.1 and 300 mm/s on a Phoenix compaction simulator. The sample set included samples with varying API content (0–50% w/w), stabilizing polymer (HPMC, HPMC-AS, PVP-VA), particle size, and bulk densities, produced on spray driers from lab to commercial scale. We identified that all ASD samples showed plastic flow and deformation behavior and form robust compacts at slow compression speeds. At high speed, tablet defects occurred. The strain rate sensitivity observed in this study was comparable or slightly superior to that observed for microcrystalline cellulose, known to be a mildly strain rate–sensitive material. We showed that compression speed is a critical process parameter for ASD-containing tablets.

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References

  1. Roberts RJ, Rowe C. 1986. The effect of the relationship between punch velocity and particle size on the compaction behaviour of materials with varying deformation mechanisms. J Pharm Pharmacol 1986; 38 (8): 567–71. https://doi.org/10.1111/j.2042-7158.1986.tb03082.x.

  2. Leane MM, Pitt K, Reynolds GK, Dawson N, Ziegler I, Szepes A, Crean AM, RDallagnol R, The Manufacturing Classification System (MCS) Working Group. Manufacturing classification system in the real world: factors influencing manufacturing process choices for filed commercial oral solid dosage formulations, case studies from industry and considerations for continuous processing. Pharm Dev Tech 2018; 23 (10): 964–77. https://doi.org/10.1080/10837450.2018.1534863.

  3. Kalaria DR, Parker K, Reynolds GK, Laru J. An industrial approach towards solid dosage development for first-in- human studies : application of predictive science and lean principles. Drug Discovery Today. 2020;25(3):505–18. https://doi.org/10.1016/j.drudis.2019.12.012.

    Article  CAS  PubMed  Google Scholar 

  4. Roberts RJ, Rowe C. The compaction of pharmaceutical and other model materials - a pragmatic approach. Chem Eng Sci. 1987;42(4):903–11.

    Article  CAS  Google Scholar 

  5. Paul S, Shao Yu Chang SY, and Changquan Calvin Sun CC. The phenomenon of tablet flashing — its impact on tableting data analysis and a method to eliminate it. Powder Technol 2017; 305: 117–24. https://doi.org/10.1016/j.powtec.2016.09.054.

  6. Tye CK, Sun CC, Amidon GE. Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction. J Pharm Sci. 2005;94(3):465–72. https://doi.org/10.1002/jps.20262.

    Article  CAS  PubMed  Google Scholar 

  7. Vig, B, Morgen M. Formulation, process development, and scale-up: spray-drying amorphous solid dispersions for insoluble drugs.” In Developing Solid Oral Dosage Forms 2017; 793–820. Elsevier Inc. https://doi.org/10.1016/B978-0-12-802447-8.00030-3.

  8. Li ChL, Martini LG, Ford JL, Roberts M. The use of hypromellose in oral drug delivery. J Pharm Pharmacol 2005; 57 (5): 533–46. https://doi.org/10.1211/0022357055957.

  9. Ekdahl A, Mudie D, Malewski D, Amidon DG, Goodwin A. Effect of spray-dried particle morphology on mechanical and flow properties of felodipine in PVP VA amorphous solid dispersions. J Pharm Sci. 2019;108(11):3657–66. https://doi.org/10.1016/j.xphs.2019.08.008.

    Article  CAS  PubMed  Google Scholar 

  10. Raman Iyer, Hegde S, Zhang YE, Dinunzio J, Singhal D, Malick A, Amidon G. The impact of hot melt extrusion and spray drying on mechanical properties and tableting indices of materials used in pharmaceutical development.” J Pharm Sci 2013; 102 (10): 3604–13. https://doi.org/10.1002/jps.23661.

  11. Stress-Strain Behaviour of Polymers. Accessed February 16, 2020. Available at: https://www.polymerdatabase.com/polymer physics/Stress-Strain Behavior.html

  12. Limbach R, Rodrigues BP, Wondraczek L. Strain-Rate Sensitivity of Glasses. J Non-Cryst Solids. 2014;404:124–34. https://doi.org/10.1016/j.jnoncrysol.2014.08.023.

    Article  CAS  Google Scholar 

  13. Nokhodchi A, Ford JL, Rowe PH, Rubinstein MH. The effects of compression rate and force on the compaction properties of different viscosity grades of hydroxypropylmethylcellulose 2208. Int J Pharm. 1996;129:21–31.

    Article  CAS  Google Scholar 

  14. Hardy IJ, Cook WG, Melia CD. Compression and compaction properties of plasticised high molecular weight hydroxypropylmethylcellulose ( HPMC ) as a Hydrophilic Matrix Carrier” Int J Pharm 2006;311: 26–32. https://doi.org/10.1016/j.ijpharm.2005.12.025.

  15. Yang L, Gopi G, Fassihi R. Characterization of Compressibility and Compactibility of Poly ( Ethylene Oxide ) Polymers for modified release application by compaction simulator. J Pharm Sci. 1996;85(10):1085–90. https://doi.org/10.1021/js960039v.

    Article  CAS  PubMed  Google Scholar 

  16. Larhrib H, Wells JI, Rubinstein MH. Compressing polyethylene glycols: the effect of compression pressure and speed. Int J Pharm. 1997;147(2):199–205. https://doi.org/10.1016/S0378-5173(96)04818-1.

    Article  CAS  Google Scholar 

  17. Ilija I, Govedarica B, Sibanc R, Dreu R, Srcic S. deformation properties of pharmaceutical excipients determined using an in-die and out-die method”. Int J Pharm. 2013;446:6–15. https://doi.org/10.1016/j.ijpharm.2013.02.001.

    Article  CAS  Google Scholar 

  18. Heckel RW. Density–pressure relationships in powder compaction. Trans Met Soc AIME. 1961;221:671–5.

    CAS  Google Scholar 

  19. Katz JM., Buckner IS. 2013. Characterization of strain rate sensitivity in pharmaceutical materials using indentation creep analysis. Int J Pharm 2013; 442 (1–2): 13–19. https://doi.org/10.1016/j.ijpharm.2012.09.006.

  20. Singh A, De Bisschop C, Schut H, Van Humbeeck J, Van Den Mooter G. Compression Effects on the phase behaviour of miconazole-poly (1-vinylpyrrolidone-co-vinyl acetate) solid dispersions - role of pressure, dwell time, and preparation method. J Pharm Sci. 2015;104(10):3366–76. https://doi.org/10.1002/jps.24540.

    Article  CAS  PubMed  Google Scholar 

  21. Leane MM, Sinclair W, Qian F, Haddadin R, Brown A, Tobyn M, Dennis AB. Formulation and Process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant”. Pharm Dev Tech. 2013;18(2):359–66. https://doi.org/10.3109/10837450.2011.619544.

    Article  CAS  Google Scholar 

  22. Pitt KG, Heasley MG. Determination of the tensile strength of elongated tablets. Powder Technol. 2013;238(February):169–75. https://doi.org/10.1016/j.powtec.2011.12.060.

    Article  CAS  Google Scholar 

  23. Sonnergaard JM. A critical evaluation of the Heckel equation. Int J Pharm. 1999;193(1):63–71. https://doi.org/10.1016/S0378-5173(99)00319-1.

    Article  CAS  PubMed  Google Scholar 

  24. Patel S, Kou X, Hou H, Huang Y, Strong JC, Zhang GGZ, Sun CC. Mechanical Properties and Tableting Behavior of Amorphous Solid Dispersions. J Pharm Sci. 2017;106:217–23. https://doi.org/10.1016/j.xphs.2016.08.021.

    Article  CAS  PubMed  Google Scholar 

  25. Patel S, Kou X, Hou HH, Huang Y, Strong JC, Zhang GGZ, Sun CC. 2017. Mechanical properties and tableting behavior of amorphous solid dispersions. J Pharm Sci 2017; 106 (1): 217–23. https://doi.org/10.1016/j.xphs.2016.08.021.

  26. Mazel V, Busignies V, Diarra H, Tchoreloff P. Lamination of pharmaceutical tablets due to air entrapment: Direct visualization and influence of the compact thickness. Int J Pharmaceutics. 2015;478:702–4. https://doi.org/10.1016/j.ijpharm.2014.12.023.

    Article  CAS  Google Scholar 

  27. Hou HH, Rajesh A, Pandya KM, Lubach JW, Muliadi A, Yost E, Jia W, Nagapudi K. Impact of method of preparation of amorphous solid dispersions on mechanical properties: comparison of coprecipitation and spray drying. J Pharm Sci. 2019;108(2):870–9. https://doi.org/10.1016/j.xphs.2018.09.008.

    Article  CAS  PubMed  Google Scholar 

  28. Agrawal AM, Dudhedia MS, Patel AD, Raikes MS. Characterization and performance assessment of solid dispersions prepared by hot melt extrusion and spray drying process. Int J Pharm. 2013;457(1):71–81. https://doi.org/10.1016/j.ijpharm.2013.08.081.

    Article  CAS  PubMed  Google Scholar 

  29. Roberts M, Ehtezazi T, Compernolle A, Amin K. 2011 The effect of spray drying on the compaction properties of hypromellose acetate succinate. Drug Dev Ind Pharm. 2011;37(3):268–73. https://doi.org/10.3109/03639045.2010.509349.

    Article  CAS  PubMed  Google Scholar 

  30. Honick MA. 2019. Itraconazole-HPMCAS amorphous spray dried dispersions : composition and process factors impacting performance. PhD thesis 2019; University of Maryland Baltimore.

  31. Amorós JL, Cantavella V, Jarque JC, Felíu C. Fracture properties of spray-dried powder compacts : effect of granule size. J Eur Ceram Soc. 2008;2008(28):2823–34. https://doi.org/10.1016/j.jeurceramsoc.2008.05.004.

    Article  CAS  Google Scholar 

  32. York P. Crystal engineering and particle design for the powder compaction process. Drug Dev Ind Pharm 1992;. Vol. 18. https://doi.org/10.3109/03639049209058558.

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Authors and Affiliations

  1. Oral Drug Product Development, Hovione FarmaCiencia SA, Estrada do Paço do Lumiar, Campus do Lumiar, Edifício S, 1649-038, Lisbon, Portugal

    S. Doktorovová & J. Henriques

  2. Merlin Powder Characterisation Ltd, Unit D1, The Wallows Industrial Estate, Fens Pool Avenue , Brierley Hill, DY5 1QA, West Midlands, UK

    E. H. Stone

Authors
  1. S. Doktorovová
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  2. E. H. Stone
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  3. J. Henriques
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Contributions

Slavomira Doktorovovová: Conceptualization, methodology, investigation, writing—original draft preparation. Elaine Harrop Stone.: Methodology, investigation, writing—reviewing and editing. João Henriques: Supervision, writing—reviewing and editing.

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Correspondence to S. Doktorovová.

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Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability

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Doktorovová, S., Stone, E.H. & Henriques, J. A Fundamental Study on Compression Properties and Strain Rate Sensitivity of Spray-Dried Amorphous Solid Dispersions. AAPS PharmSciTech 23, 96 (2022). https://doi.org/10.1208/s12249-022-02248-2

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  • DOI: https://doi.org/10.1208/s12249-022-02248-2

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