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Modulating Sticking Propensity of Pharmaceuticals Through Excipient Selection in a Direct Compression Tablet Formulation

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Abstract

Purpose

To investigate how excipient matrix affects punch sticking propensity of active pharmaceutical ingredients (API), with the focus on the effect of bonding interactions between API-API (F2) and API-excipient (F3).

Method

Sticking kinetics of direct compression formulations, consisting of 20% of celecoxib (CEL) or ibuprofen (IBN) in different excipient matrices, i.e., microcrystalline cellulose (Avicel PH102 and Avicel PH105 dry coated with nano-sized silica (PH105(n)), hypromellose (K15 M), and a 3:1 mixture between starch and Avicel PH102 (S3P1), was assessed using a removable punch tip on a compaction simulator. The amount of material transferred to punch was determined gravimetrically every 10 compressions up to 50 compactions.

Results

CEL exhibited higher F2 than IBN. CEL also exhibited more sticking under otherwise identical compaction conditions in the same excipient matrix. Among different excipient matrices, sticking propensity of both APIs followed the ascending order: PH105(n) < PH102 < K15 M < S3P1. This order was exactly opposite to the order of F3, confirming that greater bonding strength of the formulation favors lower sticking propensity of a given API.

Conclusion

For an API prone to punch sticking, judicious use of excipients to render higher tablet mechanical strength can mitigate severity of punch sticking.

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Abbreviations

F2:

API-API cohesive interaction

F3:

API-excipient adhesive interaction

CEL:

Celecoxib

εc :

Critical porosity

F4:

Excipient-excipient cohesive interaction

HPMC:

Hydroxypropyl methyl cellulose

IBN:

Ibuprofen

MCC:

Microcrystalline cellulose

1/C:

Plasticity parameter

F1:

Punch-API adhesive interaction

S3P1:

Starch + MCC (3:1)

σ:

Tablet tensile strength

σ0 :

Tensile strength at zero porosity

References

  1. Abdel-Hamid S, Betz G. A novel tool for the prediction of tablet sticking during high speed compaction. Pharm Dev Technol. 2012;17(6):747–54.

    Article  PubMed  CAS  Google Scholar 

  2. Otsuka A. Adhesive properties and related phenomena for powdered pharmaceuticals. Yakugaku Zasshi. 1998;118(4):127–42.

    Article  PubMed  CAS  Google Scholar 

  3. Al-Karawi C, Lukášová I, Sakmann A, Leopold CS. Novel aspects on the direct compaction of ibuprofen with special focus on sticking. Powder Technol. 2017;317(Supplement C):370–80.

    Article  CAS  Google Scholar 

  4. McDermott TS, Farrenkopf J, Hlinak A, Neilly JP, Sauer D. A material sparing method for quantitatively measuring tablet sticking. Powder Technol. 2011;212(1):240–52.

    Article  CAS  Google Scholar 

  5. Paul S, Taylor LJ, Murphy B, Krzyzaniak JF, Dawson N, Mullarney MP, et al. Powder properties and compaction parameters that influence punch sticking propensity of pharmaceuticals. Int J Pharm. 2017;521(1–2):374–83.

    Article  PubMed  CAS  Google Scholar 

  6. Waknis V, Chu E, Schlam R, Sidorenko A, Badawy S, Yin S, et al. Molecular basis of crystal morphology-dependent adhesion behavior of mefenamic acid during tableting. Pharm Res. 2014;31(1):160–72.

    Article  PubMed  CAS  Google Scholar 

  7. Paul S, Wang K, Taylor LJ, Murphy B, Krzyzaniak J, Dawson N, et al. Dependence of punch sticking on compaction pressure-roles of particle deformability and tablet tensile strength. J Pharm Sci. 2017;106(8):2060–7.

    Article  PubMed  CAS  Google Scholar 

  8. Hooper D, Clarke FC, Docherty R, Mitchell JC, Snowden MJ. Effects of crystal habit on the sticking propensity of ibuprofen—A case study. Int J Pharm. 2017;531(1):266–75.

    Article  PubMed  CAS  Google Scholar 

  9. Tsosie H, Thomas J, Strong J, Zavaliangos A. Scanning electron microscope observations of powder sticking on punches during a limited number (N < 5) of compactions of acetylsalicylic acid. Pharm Res. 2017;34(10):2012–24.

    Article  PubMed  CAS  Google Scholar 

  10. Corn M. The adhesion of solid particles to solid surfaces. II. J Air Pollut Control Assoc. 1961;11(12):566–84.

    Article  PubMed  CAS  Google Scholar 

  11. Corn M. The adhesion of solid particles to solid surfaces, I. a review. J Air Pollut Control Assoc. 1961;11(11):523–8.

    Article  PubMed  CAS  Google Scholar 

  12. Roberts M, Ford JL, MacLeod GS, Fell JT, Smith GW, Rowe PH. Effects of surface roughness and chrome plating of punch tips on the sticking tendencies of model ibuprofen formulations. J Pharm Pharmacol. 2003;55(9):1223–8.

    Article  PubMed  CAS  Google Scholar 

  13. Roberts M, Ford JL, MacLeod GS, Fell JT, Smith GW, Rowe PH, et al. Effect of punch tip geometry and embossment on the punch tip adherence of a model ibuprofen formulation. J Pharm Pharmacol. 2004;56(7):947–50.

    Article  PubMed  CAS  Google Scholar 

  14. Samiei L, Kelly K, Taylor L, Forbes B, Collins E, Rowland M. The influence of electrostatic properties on the punch sticking propensity of pharmaceutical blends. Powder Technol. 2017;305(Supplement C):509–17.

    Article  CAS  Google Scholar 

  15. Al-Karawi C, Kaiser T, Leopold CS. A novel technique for the visualization of tablet punch surfaces: characterization of surface modification, wear and sticking. Int J Pharm. 2017;530(1):440–54.

    Article  PubMed  CAS  Google Scholar 

  16. Reed K, Davies C, Kelly K. Tablet sticking: using a ‘compression toolbox’ to assess multiple tooling coatings options. Powder Technol. 2015;285(Supplement C):103–9.

    Article  CAS  Google Scholar 

  17. Paul S, Taylor LJ, Murphy B, Krzyzaniak J, Dawson N, Mullarney MP, et al. Mechanism and kinetics of punch sticking of pharmaceuticals. J Pharm Sci. 2017;106(1):151–8.

    Article  PubMed  CAS  Google Scholar 

  18. Uchimoto T, Iwao Y, Yamamoto T, Sawaguchi K, Moriuchi T, Noguchi S, et al. Newly developed surface modification punches treated with alloying techniques reduce sticking during the manufacture of ibuprofen tablets. Int J Pharm. 2013;441(1–2):128–34.

    Article  PubMed  CAS  Google Scholar 

  19. Chattoraj S, Shi L, Sun CC. Profoundly improving flow properties of a cohesive cellulose powder by surface coating with nano-silica through comilling. J Pharm Sci. 2011;100(11):4943–52.

    Article  PubMed  CAS  Google Scholar 

  20. Kuentz M, Leuenberger H. Pressure susceptibility of polymer tablets as a critical property: a modified Heckel equation. J Pharm Sci. 1999;88(2):174–9.

    Article  PubMed  CAS  Google Scholar 

  21. Sun CC. Microstructure of tablet—pharmaceutical significance, assessment, and engineering. Pharm Res. 2017;34(5):918–28.

    Article  PubMed  CAS  Google Scholar 

  22. Paul S, Sun CC. The suitability of common compressibility equations for characterizing plasticity of diverse powders. Int J Pharm. 2017;532:124–30.

    Article  PubMed  CAS  Google Scholar 

  23. Sun CC. A novel method for deriving true density of pharmaceutical solids including hydrates and water-containing powders. J Pharm Sci. 2004;93(3):646–53.

    Article  PubMed  CAS  Google Scholar 

  24. Sun CC. True density of microcrystalline cellulose. J Pharm Sci. 2005;94(10):2132–4.

    Article  PubMed  CAS  Google Scholar 

  25. Sun CC. Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose. Int J Pharm. 2008;346(1–2):93–101.

    Article  PubMed  CAS  Google Scholar 

  26. Chang SY, Sun CC. Superior plasticity and tabletability of theophylline monohydrate. Mol Pharm. 2017;14(6):2047–55.

    Article  PubMed  CAS  Google Scholar 

  27. Sun CC. Quantifying errors in tableting data analysis using the Ryshkewitch equation due to inaccurate true density. J Pharm Sci. 2005;94(9):2061–8.

    Article  PubMed  CAS  Google Scholar 

  28. Paul S, Chang SY, 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.

    Article  CAS  Google Scholar 

  29. Fell JT, Newton JM. Determination of tablet strength by the diametral-compression test. J Pharm Sci. 1970;59(5):688–91.

    Article  PubMed  CAS  Google Scholar 

  30. Ryshkewitch E. Compression strength of porous sintered alumina and zirconia. J Am Cerac Soc. 1953;36(2):65–8.

    Article  Google Scholar 

  31. Osei-Yeboah F, Sun CC. A pitfall in analyzing powder compactibility data using nonlinear regression. J Pharm Sci. 2013;102(3):1135–6.

    Article  PubMed  CAS  Google Scholar 

  32. Shi L, Sun CC. Transforming powder mechanical properties by core/shell structure: compressible sand. J Pharm Sci. 2010;99:4458–62.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Sun CC. Decoding powder tabletability: roles of particle adhesion and plasticity. J Adhes Sci Technol. 2011;25(4–5):483–99.

    Article  CAS  Google Scholar 

  35. Osei-Yeboah F, Chang SY, Sun CC. A critical examination of the phenomenon of bonding Area - bonding strength interplay in powder tableting. Pharm Res. 2016;33(5):1126–32.

    Article  PubMed  CAS  Google Scholar 

  36. Osei-Yeboah F, Lan Y, Sun CC. A top coating strategy with highly bonding polymers to enable direct tableting of multiple unit pellet system (MUPS). Powder Technol. 2017;305:591–6.

    Article  CAS  Google Scholar 

  37. Swaminathan S, Ramey B, Hilden J, Wassgren C. Characterizing the powder punch-face adhesive interaction during the unloading phase of powder compaction. Powder Technol. 2017;315:410–21.

    Article  CAS  Google Scholar 

  38. Perumalla SR, Shi L, Sun CC. Ionized form of acetaminophen with improved compaction properties. CrystEngComm. 2012;14(7):2389–90.

    Article  CAS  Google Scholar 

  39. Alderborn G, Nystrom C. Radial and axial tensile strength and strength variability of paracetamol tablets. Acta Pharm Suec. 1984;21(1):1–8.

    PubMed  CAS  Google Scholar 

  40. Wu CY, Ruddy OM, Bentham AC, Hancock BC, Best SM, Elliott JA. Modelling the mechanical behaviour of pharmaceutical powders during compaction. Powder Technol. 2005;52(1–3):107–17.

    Article  CAS  Google Scholar 

  41. Patel S, Sun CC. Macroindentation hardness measurement-modernization and applications. Int J Pharm. 2016;506(1–2):262–7.

    Article  PubMed  CAS  Google Scholar 

  42. Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients, 6th edn. 2009.

  43. Cui Y. A material science perspective of pharmaceutical solids. Int J Pharm. 2007;339:3–18.

    Article  PubMed  CAS  Google Scholar 

  44. Heng PWS, Chan LW, Easterbrook MG, Li X. Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets. J Control Release. 2001;76(1):39–49.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pharmaceutical Materials Science and Engineering Laboratory Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota, 55455, USA

    Shubhajit Paul & Changquan Calvin Sun

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  1. Shubhajit Paul
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  2. Changquan Calvin Sun
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Correspondence to Changquan Calvin Sun.

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Paul, S., Sun, C.C. Modulating Sticking Propensity of Pharmaceuticals Through Excipient Selection in a Direct Compression Tablet Formulation. Pharm Res 35, 113 (2018). https://doi.org/10.1007/s11095-018-2396-3

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  • DOI: https://doi.org/10.1007/s11095-018-2396-3

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