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AAPS PharmSciTech

, 20:168 | Cite as

Investigating the Effect of APAP Crystals on Tablet Behavior Manufactured by Direct Compression

  • Nastaran GhaziEmail author
  • Zhanjie Liu
  • Chinmay Bhatt
  • San Kiang
  • Alberto Cuitino
Research Article

Abstract

In this work, the effect of API’s (Active Pharmaceutical Ingredient) shape and size on tablet characteristics is investigated for high API dose formulation manufactured by direct compression. Three different classes of APAP (acetaminophen) are selected, and tablets are produced in both single and batch processes. After performing and comparing comprehensive series of standard characterization tests including hardness, dissolution, disintegration, and friability on the tablets, the test results show the relation between the quality of APAP tablets and the shape and size of the crystals. We also investigate the effect of scaling up the manufacturing process (from single to batch) by evaluating dosage uniformity and possibility of segregation in blends. The results indicate a strong interaction between manufacturing parameters such as speed and scale of production to API crystal size and shape. This places crystal properties in the critical parameter set that requires tracking and monitoring in order to maintain consistent tablet properties in high-dose formulation continuous manufacturing operations.

Key Words

APAP direct compression high-dose API API crystals tablet properties 

Notes

Funding information

The authors gratefully acknowledge the support provided from the National Science Foundation (NSF)-ERC center and NSF-SAVI grant.

References

  1. 1.
    Capece M, Huang Z, Davé R. Insight into a novel strategy for the design of tablet formulations intended for direct compression. J Pharm Sci. 2017;106(6):1608–17.CrossRefGoogle Scholar
  2. 2.
    Schmidt PC. Pharmaceutical dosage forms: tablets. 2nd ed. New York-basel: Marcel Dekker, Inc; 1990.Google Scholar
  3. 3.
    Gupta V, Mutalik S, Patel M, Jani G. Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties. Acta Pharma. 2007;57:173–84.CrossRefGoogle Scholar
  4. 4.
    Jivraj M, Martini LG, Thomson CM. An overview of the different excipients useful for the direct compression of tablets. Pharm Sci Technol Today. 2000;3(2):58–63.CrossRefGoogle Scholar
  5. 5.
    McCormick D. Evolutions in direct compression. Pharm Technol. 2005;17(4):52–62.Google Scholar
  6. 6.
    Leane M, Pitt K, Reynolds G, Group MCSW. A proposal for a drug product manufacturing classification system (MCS) for oral solid dosage forms. Pharm Dev Technol. 2015;20(1):12–21.CrossRefGoogle Scholar
  7. 7.
    Krycer I, Pope DG, Hersey JA. The prediction of paracetamol capping tendencies. J Pharm Pharmacol. 1982;34(12):802–4.CrossRefGoogle Scholar
  8. 8.
    Nyström C, Mazur J, Sjögren J. Studies on direct compression of tablets II. The influence of the particle size of a dry binder on the mechanical strength of tablets. Int J Pharm. 1982;10(3):209–18.CrossRefGoogle Scholar
  9. 9.
    Kolter K, Flick D. Structure and dry binding activity of different polymers, including Kollidon® VA 64. Drug Dev Ind Pharm. 2000;26(11):1159–65.CrossRefGoogle Scholar
  10. 10.
    Zuurman K, Riepma KA, Bolhuis GK, Vromans H, Lerk CF. The relationship between bulk density and compactibility of lactose granulations. Int J Pharm. 1994;102:1–9.CrossRefGoogle Scholar
  11. 11.
    Humbert-droz P, Gurny R, Mordier D, Doelker E. Densification behaviour of drugs presenting availability problems. Int J Pharm Technol Prod Manuf. 1983; 29–35 p.Google Scholar
  12. 12.
    Huttenrauch R. Modification of starting materials to improve tabletting properties. Pharm Ind. 1983;45(4):435–40.Google Scholar
  13. 13.
    Shotton E, Obiorah BA. The effect of particle shape and crystal habit on properties of sodium chloride. J Pharm Pharmacol. 1973;25(Suppl):37P–43P.Google Scholar
  14. 14.
    Van Der Voort MK, Bolhuis GK. Improving properties of materials for direct compaction. Pharm Technol. 1999;23(5):34–46.Google Scholar
  15. 15.
    Blagden N, De Matas M, Gavan P, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev. 2007;59(7):617–30.CrossRefGoogle Scholar
  16. 16.
    Sheth PR, Wiley JH, inventors; Wyeth Holdings LLC assignee. Calcium phosphates in tablet compressing patent US3134719A. 1964 1962.Google Scholar
  17. 17.
    Joiris E, Di Martino P, Berneron C, Guyot-Hermann A-M, Guyot J-C. Compression behavior of orthorhombic paracetamol. Pharm Res. 1998;15(7):1122–30.CrossRefGoogle Scholar
  18. 18.
    Tiwary A. Modification of crystal habit and its role in dosage form performance. Drug Dev Ind Pharm. 2001;27(7):699–709.CrossRefGoogle Scholar
  19. 19.
    Rasenack N, Müller BW. Crystal habit and tableting behavior. Int J Pharm. 2002;244(1):45–57.CrossRefGoogle Scholar
  20. 20.
    Fachaux JM, Guyot-Hermann AM, Guyot JC, Conflant P, Drache M, Veesler S, et al. Pure Paracetamol for direct compression part II. Study of the physicochemical and mechanical properties of sintered-like crystals of Paracetamol. Powder Technol. 1995;82(2):129–33.CrossRefGoogle Scholar
  21. 21.
    Di Martino P, Guyot-Hermann AM, Conflant P, Drache M, Guyot JC. A new pure paracetamol for direct compression: the orthorhombic form. Int J Pharm. 1996;128(1):1–8.CrossRefGoogle Scholar
  22. 22.
    Govedarica B, Injac R, Srcic S. Formulation and evaluation of immediate release tablets with different types of paracetamol powders prepared by direct compression. Afr J Pharm Pharmacol. 2009;5(1):31–41.CrossRefGoogle Scholar
  23. 23.
    Martinello T, Kaneko TM, Velasco MVR, Taqueda MES, Consiglieri VO. Optimization of poorly compactable drug tablets manufactured by direct compression using the mixture experimental design. Int J Pharm. 2006;322(1):87–95.CrossRefGoogle Scholar
  24. 24.
    Pitt KG, Webber RJ, Hill KA, Dey D, Gamlen MJ. Compression prediction accuracy from small scale compaction studies to production presses. Powder Technol. 2015;270:490–3.CrossRefGoogle Scholar
  25. 25.
    Osamura T, Takeuchi Y, Onodera R, Kitamura M, Takahashi Y, Tahara K, et al. Prediction of effects of punch shapes on tableting failure by using a multi-functional single-punch tablet press. Asian J Pharm. 2017;12(5):412–7.Google Scholar
  26. 26.
    Yogananda R, Nagaraja T, Snehalatha JK, Vijay KM. Comparative in vitro equivalence studies of designed, branded and generic tablets of ciprofloxacin-250. Int J Pharm Sci. 2009;1(1):28–34.Google Scholar
  27. 27.
    Al-Zoubi N, Nikolakakis I, Malamataris S. Crystallization conditions and formation of orthorhombic paracetamol from ethanolic solution. J Pharm Pharmacol. 2002;54(3):325–33.CrossRefGoogle Scholar
  28. 28.
    Lerk C, Bolhuis G, Smedema S. Interaction of lubricants and colloidal silica during mixing with excipients. I. Its effect on tabletting. Pharm Acta Helv. 1977;52(3):33.Google Scholar
  29. 29.
    Lamberson RF, Raynor GE. Tableting properties of microcrystalline cellulose. Manuf Chem Aerosol News. 1976;47(6):55–61.Google Scholar
  30. 30.
    Raymond CR, Paul JS, Walter GC, Marian EQ. Handbook of pharmaceutical excipients. 7th ed. Washington DC: The American Pharmacists Association; 2012. 1033 p.Google Scholar
  31. 31.
    Sun CC. True density of microcrystalline cellulose. J Pharm Sci. 2005;94(10):2132–4.CrossRefGoogle Scholar
  32. 32.
    Moroni A. A novel copovidone binder for dry granulation and direct-compression tableting. Pharm Technol. 2001;25(9; SUPP):8–13.Google Scholar
  33. 33.
    Kornblum S, Stoopak S. A new tablet disintegrating agent: cross-linked polyvinylpyrrolidone. J Pharm Sci. 1973;62(1):43–9.CrossRefGoogle Scholar
  34. 34.
    Jonat S, Hasenzahl S, Gray A, Schmidt PC. Influence of compacted hydrophobic and hydrophilic colloidal silicon dioxide on tableting properties of pharmaceutical excipients. Drug Dev Ind Pharm. 2005;31(7):687–96.CrossRefGoogle Scholar
  35. 35.
    Hussain MSH, York P, Timmins P. A study of the formation of magnesium stearate film on sodium chloride using energy-dispersive X-ray analysis. Int J Pharm. 1988;42(1):89–95.CrossRefGoogle Scholar
  36. 36.
    The merck index. An encyclopedia of chemicals, drugs, and biologicals. Tenth Edition. 2, 067 pp. (including tables and index) [Internet]. Merck & Co., Inc. 1983. Available from:  https://doi.org/10.1002/hep.1840050135.
  37. 37.
    Edwards LD, Fletcher AJ, Fox AW, Stonier PD. Principles and practice of pharmaceutical medicine. 2nd ed: John Wiley & Sons, Ltd; 2007.Google Scholar
  38. 38.
    Aleeva GN, Zhuravleva MV, Khafiz’yanova RK. The role of excipients in determining the pharmaceutical and therapeutic properties of medicinal agents (review). Pharm Chem J. 2009;43(4):230–4.CrossRefGoogle Scholar
  39. 39.
    US Pharmacopia [Internet]. 2018. Available from: http://www.usp.org.
  40. 40.
    Ruiz AM, Jimenez-castellanos MR, Cunningham JC, Katdare AV. Theoretical estimation of dwell and consolidation times in rotary tablet machines. Drug Dev Ind Pharm. 1992;18(19):2011–28.CrossRefGoogle Scholar
  41. 41.
    Schulze D. Powder and bulk solids. 1 ed. Berlin: Springer-Verlag; 2008.Google Scholar
  42. 42.
    Kleinebudde P, Khinast J, Rantanen J. Continious manufacturing of pharmaceuticals. 1st ed: John Wiley & Sons; 2017. 620 p.Google Scholar
  43. 43.
    Purutyan H, Carson JW. Predicting, diagnosing, and solving mixture segregation problems2007.Google Scholar
  44. 44.
    Williams JC. The segregation of particulate materials. A review. Powder Technol. 1976;15(2):245–51.CrossRefGoogle Scholar
  45. 45.
    ASTM-International. Standard practice for measuring sifting segregation tendencies of bulk solids. ASTM D6940-03. West Conshohocken, PA2003.Google Scholar
  46. 46.
    Fell J, Newton J. Determination of tablet strength by the diametral-compression test. J Pharm Sci. 1970;59(5):688–91.CrossRefGoogle Scholar
  47. 47.
    Hogg R. Mixing and segregation in powders: evaluation, mechanisms and processes. KONA Powder and Particle Journal. 2009;27:3–17.CrossRefGoogle Scholar
  48. 48.
    Rogers AJ, Hashemi A, Ierapetritou MG. Modeling of particulate processes for the continuous manufacture of solid-based pharmaceutical dosage forms. Processes. 2013;1(2):67–127.CrossRefGoogle Scholar
  49. 49.
    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.CrossRefGoogle Scholar
  50. 50.
    Li J, Wu Y. Lubricants in pharmaceutical solid dosage forms. Lubricants. 2014;2(1):21–43.CrossRefGoogle Scholar
  51. 51.
    Carstensen JT. Pharmaceutical of solids and solid dosage forms. New York: Wiley; 1977. 256 p.Google Scholar
  52. 52.
    Wang Y, Liu Z, Muzzio F, Drazer G, Callegari G. A drop penetration method to measure powder blend wettability. Int J Pharm. 2017;538(1–2):112–8.PubMedGoogle Scholar
  53. 53.
    Wang Y, Osorio JG, Li T, Muzzio FJ. Controlled shear system and resonant acoustic mixing: effects on lubrication and flow properties of pharmaceutical blends. Powder Technol. 2017;322:332–9.CrossRefGoogle Scholar
  54. 54.
    Akande OF, Ford JL, Rowe PH, Rubinstein MH. Pharmaceutics: the effects of lag-time and dwell-time on the compaction properties of 1: 1 Paracetamol/microcrystalline cellulose tablets prepared by pre-compression and main compression. J Pharm Pharmacol. 1998;50(1):19–28.CrossRefGoogle Scholar
  55. 55.
    Markl D, Zeitler JA. A review of disintegration mechanisms and measurement techniques. Pharm Res. 2017;34(5):890–917.CrossRefGoogle Scholar
  56. 56.
    Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharmaceutics. 2012;2012:1–10.CrossRefGoogle Scholar
  57. 57.
    Unno J, Umeda R, Hirasawa I. Computing crystal size distribution by focused-beam reflectance measurement when aspect ratio varies. Chem Eng Technol. 2018;41(6):1147–51.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Nastaran Ghazi
    • 1
    • 2
    Email author
  • Zhanjie Liu
    • 2
    • 3
  • Chinmay Bhatt
    • 2
    • 3
  • San Kiang
    • 2
    • 3
  • Alberto Cuitino
    • 1
    • 2
  1. 1.Department of Mechanical and Aerospace EngineeringRutgers UniversityPiscatawayUSA
  2. 2.Center for structured organic particulate systemsRutgers UniversityNew BrunswickUSA
  3. 3.Department of Chemical and Biochemical EngineeringRutgers UniversityNew BrunswickUSA

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