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Particle Engineering: Fundamentals of Particle Formation and Crystal Growth

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Abstract

The engineering of particles with customized properties optimized for dosage form manufacture (tablet, capsule, ointment, etc.) has long been a goal of the pharmaceutical industry. Particles can be designed through modification in the size, morphology, and packing arrangement of the solids. The most common approach in achieving this is through crystallization. In this bottom-up process, the two main steps, nucleation and crystal growth, both play a decisive role in shaping the quality of the final crystalline product. In this review, the role of nucleation and crystal growth in controlling particle properties is discussed, and examples are provided that demonstrate the variation in solid-state properties as a function of size, habit (morphology), and internal structure of the particles. In addition, the role of particle properties in product performance and dosage form development of pharmaceuticals is also discussed.

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References

  1. E.L. Paul, H.H. Tung, and M. Midler, Powd. Technol. 150 (2005) p. 133.

    Google Scholar 

  2. B.Y. Shekunov and P. York, J. Cryst. Growth 211 (2000) p. 122.

    Google Scholar 

  3. 3. G. Desiraju, Crystal Engineering: The Design of Organic Solids (Elsevier, Amsterdam, 1989).

    Google Scholar 

  4. P. Erk, H. Hengelsberg, M.F. Haddow, and R. Van Gelder, Cryst. Eng. Comm. 6 (2004) p. 474.

    Google Scholar 

  5. M. Volmer, Kinetik der Phasenbildung (Steinkopff, Germany, 1939).

    Google Scholar 

  6. D.W. Oxtoby, Acc. Chem. Res. 31 (1998) p. 91.

    Google Scholar 

  7. P.G. Vekilov, Cryst. Growth Des. 4 (2004) p. 671.

    Google Scholar 

  8. F. Schuth, Curr. Opin. Solid State Mater. Sci. 5 (2001) p. 389.

    Google Scholar 

  9. D.W. Oxtoby, Philos. Trans. R. Soc. London, Ser. A. 361 (2003) p. 419.

    Google Scholar 

  10. P.R. ten Wolde and D. Frenkel, Science 277 (1997) p. 1975.

    Google Scholar 

  11. J.D. Shore, D. Perchak, and Y. Shnidman, J. Chem. Phys. 113 (2000) p. 6276.

    Google Scholar 

  12. O. Galkin and P.G. Vekilov, J. Am. Chem. Soc. 122 (2000) p. 156.

    Google Scholar 

  13. S. Chattopadhyay, D. Erdemir, J.M.B. Evans, J. Ilavsky, H. Amenitsch, C.U. Segre, and A.S. Myerson, Cryst. Growth. Des. 5 (2005) p. 523.

    Google Scholar 

  14. M. Kimura, Cryst. Growth Des. 6 (2006) p. 854.

    Google Scholar 

  15. B.A. Garetz, J. Matic, and A.S. Myerson, Phys. Rev. Lett. 89 175501 (2002).

    Google Scholar 

  16. R.J. Davey, K. Allen, N. Blagden, W.I. Cross, H.F. Lieberman, M.J. Quayle, S. Righini, L. Seton, and G.J.T. Tiddy, Cryst. Eng. Comm. 4 (2002) p. 257.

    Google Scholar 

  17. R. Hilfiker, Ed., Polymorphism in the Pharmaceutical Industry (John Wiley & Sons, Chichester, 2006); G. Winter, in Reactivity of Molecular Solids, edited by E.V. Boldyreva and V.V. Boldyrev (John Wiley & Sons, Chichester, 1999) p. 241.

    Google Scholar 

  18. J. Bernstein, Polymorphism in Molecular Crystals (Oxford University Press, New York, 2002).

    Google Scholar 

  19. J.O. Henck, U.J. Griesser, and A. Burger, Pharm. Ind. 59 (1997) p. 165.

    Google Scholar 

  20. M.R. Caira, in Topics in Current Chemistry, Vol. 198, edited by E. Weber (Springer, New York, 1998) p. 163.

    Google Scholar 

  21. S. Briancon and H. Fessi, STP Pharma. Prat. 13 (2003) p. 215; E. Doelker, STP Pharma. Prat. 9 (1999) p. 399.

    Google Scholar 

  22. C. Sun and D.J.W. Grant, Pharm. Res. 18 (2001) p. 274; C. Sun and D.J.W. Grant, Pharm. Res. 21 (2004) p. 382.

    Google Scholar 

  23. X. Chen, K.R. Morris, U.J. Griesser, S.R. Byrn, and J.G. Stowell, J. Am. Chem. Soc. 124 (2002) p. 15012.

    Google Scholar 

  24. J.D. Dunitz and J. Bernstein, Acc. Chem. Res. 28 (1995) p. 193.

    Google Scholar 

  25. A. Gavezzotti and G. Filippini, J. Am. Chem. Soc. 117 (1995) p. 12299.

    Google Scholar 

  26. J. Bauer, S. Spanton, R. Henry, J. Quick, W. Dziki, W. Porter, and J. Morris, Pharm. Res. 18 (2001) p. 859.

    Google Scholar 

  27. J.K. Guillory, in Polymorphism in Pharmaceutical Solids, edited by H.G. Brittain (Marcel Dekker, New York, 1999) p. 183; M. Maiwald, Am. Pharm. Rev. 9 (2006) p. 95.

    Google Scholar 

  28. M. Janik, Z. Malarski, J. Mrozinski, J. Wajcht, and Z. Zborucki, J. Crystallogr. Spectrosc. Res. 21 (1991) p. 519.

    Google Scholar 

  29. S.L. Morissette, O. Almarsson, M.L. Peterson, J.F. Remenar, M.J. Read, A.V. Lemmo, S. Ellis, M.J. Cima, and C.R. Gardner, Adv. Drug Delivery Rev. 56 (2004) p. 275.

    Google Scholar 

  30. H. Furedi-Milhofer, N. Garti, and A. Kamyshny, J. Cryst. Growth 198–199 (1999) p. 1365.

    Google Scholar 

  31. J.M. Ha, J.H. Wolf, M.A. Hillmyer, and M.D. Ward, J. Am. Chem. Soc. 126 (2004) p. 3382.

    Google Scholar 

  32. A.Y. Lee, I.S. Lee, S.S. Dette, J. Boerner, and A.S. Myerson, J. Am. Chem. Soc. 127 (2005) p. 14982.

    Google Scholar 

  33. C.P. Price, A.L. Grzesiak, and A.J. Matzger, J. Am. Chem. Soc. 127 (2005) p. 5512.

    Google Scholar 

  34. R. Hiremath, J.A. Basile, S.W. Varney, and J.A. Swift, J. Am. Chem. Soc. 127 (2005) p. 18321.

    Google Scholar 

  35. S. Chen, H. Xi, and L. Yu, J. Am. Chem. Soc. 127 (2005) p. 17439.

    Google Scholar 

  36. M.C. Meyer, A.B. Straughn, E.J. Jaryi, G.C. Wood, F.R. Pelsor, and V.P. Shah, Pharm. Res. 9 (1992) p. 1612.

    Google Scholar 

  37. S.L. Price, Adv. Drug. Delivery Rev. 56 (2004) p. 301.

    Google Scholar 

  38. R. Docherty and P. Meenan, in Molecular Modeling Applications in Crystallization, edited by A.S. Myerson (Cambridge University Press, Cambridge, 1999) p. 106.

    Google Scholar 

  39. P. Verwer and F.J.J. Leusen, in Reviews in Computational Chemistry, Vol. 12, edited by K.B. Lipkowitz and D.B. Boyd (John Wiley & Sons, New York, 1998) p. 327; R.J. Gdanitz, Curr. Opin. Solid State Mater. Sci. 3 (1998) p. 414.

    Google Scholar 

  40. J.P.M. Lommerse, W.D.S. Motherwell, H.L. Ammon, J.D. Dunitz, A. Gavezzotti, D.W.M. Hofmann, F.J.J. Leusen, W.T.M. Mooij, S.L. Price, B. Schweizer, M.U. Schmidt, B.P van Eijck, P. Verwer, and D.E. Williams, Acta Crystallogr., Sect. B: Struct. Sci. 56 (2000) p. 697; W.D.S. Motherwell, H.L. Ammon, J.D. Dunitz, A. Dzyabchenko, P. Erk, A. Gavezzotti, D.W.M. Hofmann, F.J.J. Leusen, J.P.M. Lommerse, W.T.M. Mooij, P. Verwer, and D.E. Williams, Acta Crystallogr., Sect. B: Struct. Sci. 58 (2002) p. 647; G.M. Day, W.D.S. Motherwell, H.L. Ammon, S.X.M. Boerrigter, R.G. Della Valle, E. Venuti, A. Dzvabchenko, J.D. Dunitz, B. Schweizer, B.P. van Eijck, P. Erk, J.C. Facelli, V.E. Bazterra, M.B. Ferraro, D.W.M. Hofmann, F.J.J. Leusen, C. Liang, C.C. Pantelides, P.G. Karamertzanis, S.L. Price, T.C. Lewis, H. Nowell, A. Torrisi, H.A. Scheraga, Y.A. Arnautova, M.U. Schmidt, and P. Verwer, Acta Crystallogr., Sect. B: Struct. Sci. 61 (2005) p. 511.

    Google Scholar 

  41. S.L. Price, in Reviews in Computational Chemistry, Vol. 14, edited by K.B. Lipkowitz and D.B. Boyd (John Wiley & Sons, New York, 2000) p. 225.

    Google Scholar 

  42. T. Beyer, T. Lewis, and S.L. Price, Cryst. Eng. Comm. 44 (2001) p. 1.

    Google Scholar 

  43. J.D. Dunitz, Chem. Commun. (2003) p. 545.

  44. J.K. Haleblian, J. Pharm. Sci. 64 (1975) p. 1269.

    Google Scholar 

  45. E.M. Walker, K.J. Roberts, and S.J. Maginn, Langmuir 14 (1998) p. 5620.

    Google Scholar 

  46. I. Weissbuch, R. Popovitz-Biro, M. Lahav, and L. Leiserowitz, Acta Crystallogr., Sect. B: Struct. Sci. 51 (1995) p. 115.

    Google Scholar 

  47. L. Addadi, S. Weinstein, E. Gati, I. Weissbuch, and M. Lahav, J. Am. Chem. Soc. 104 (1982) p. 4610.

    Google Scholar 

  48. L. Addadi, Z. Berkovitch-Yellin, I. Weissbuch, M. Lahav, and L. Leiserowitz, Mol. Cryst. Liq. Cryst. 96 (1982) p. 1.

    Google Scholar 

  49. R.J. Davey, N. Blagden, G.D. Potts, and R. Docherty, J. Am. Chem. Soc. 119 (1997) p. 1767; T. Mukuta, A.Y. Lee, T. Kawakami, and A.S Myerson, Cryst. Growth Des. 5 (2005) p. 1429.

    Google Scholar 

  50. L. Addadi, Z. Berkovitch-Yellin, N. Domb, E. Gati, M. Lahav, and L. Leiserowitz, Nature 296 (1982) p. 21.

    Google Scholar 

  51. B. Kahr and R.W. Gurney, Chem. Rev. 101 (2001) p. 893.

    Google Scholar 

  52. H. Colfen and L. Qi, Chem. Eur. J. 7 (2001) p. 106.

    Google Scholar 

  53. A. Kuldipkumar, Y.T.F. Tan, M. Goldstein, Y. Nagasaki, G.G.Z. Zhang, and G.S. Kwon, Cryst. Growth Des. 5 (2005) p. 1781.

    Google Scholar 

  54. N. Rasenack and B.W. Muller, Int. J. Pharm. 244 (2002) p. 45.

    Google Scholar 

  55. G.M. Khan and Z. Jiabi, Drug Dev. Ind. Pharm. 24 (1998) p. 463.

    Google Scholar 

  56. W.M.L. Wood, Powd. Technol. 121 (2001) p. 53.

    Google Scholar 

  57. V. Chikhalia, R.T. Forbes, R.A. Storey, and M. Ticehurst, Eur. J. Pharm. Sci. 27 (2006) p. 19.

    Google Scholar 

  58. X.M. Zeng, G.P. Martin, C. Marriott, and J. Pritchard, Int. J. Pharm. 200 (2000) p. 93.

    Google Scholar 

  59. M. Brunsteiner and S.L Price, Cryst. Growth Des. 1 (2001) p. 447.

    Google Scholar 

  60. X.Y. Liu, E.S. Boek, W.J. Briels, and P. Bennema, Nature 374 (1995) p. 342; D. Winn and M.F. Doherty, AIChe J. 44 (1998) p. 2501.

    Google Scholar 

  61. S.X.M. Boerrigter, H.M. Cuppen, R.I. Ristic, J.N. Sherwood, P. Bennema, and H. Meekes, Cryst. Growth. Des. 2 (2002) p. 357.

    Google Scholar 

  62. Z. Berkovitch-Yellin, J. Am. Chem. Soc. 107 (1985) p. 8239.

    Google Scholar 

  63. P. Mougin, G. Clydesdale, R.B. Hammond, and K.J. Roberts, J. Phys. Chem. B 107 (2003) p. 13262.

    Google Scholar 

  64. A.J. Hickey, ed., Pharmaceutical Inhalation Aerosol Technology (Marcel Dekker, New York, 1992).

    Google Scholar 

  65. C.A. Lipinski, Am. Pharm. Rev. 5 (2002) p. 82.

    Google Scholar 

  66. D. Horn and J. Rieger, Angew. Chem. Int. Ed. 40 (2001) p. 4330.

    Google Scholar 

  67. G.G. Liversidge and K.C. Cundy, Int. J. Pharm. 125 (1995) p. 91.

    Google Scholar 

  68. T.P. Shakhtshneider and V.V. Boldyrev, in Reactivity of Molecular Solids, edited by E.V. Boldyreva and V.V. Boldyrev (John Wiley & Sons, Chichester, 1999) p. 271.

    Google Scholar 

  69. J.E. Kipp, Int. J. Pharm. 284 (2004) p. 109; B.E. Rabinow, Nat. Rev. Drug Disc. 3 (2004) p. 785.

    Google Scholar 

  70. M. Midler Jr., E.P. Paul, E.F. Whittington, M. Futran, P.D. Liu, J. Hsu, and S.H. Pan, “Crystallization method to improve crystal structure and size,” U.S. Patent No. 5,314,506 (May 24, 1994).

  71. P. York, U.B. Kompella, and B.Y. Shekunov, eds., Supercritical Fluid Technology for Drug Product Development (Marcel Dekker, New York, 2004).

    Google Scholar 

  72. M. Sacchetti and M.M. Van Oort, in Inhalation Aerosols, edited by A.J. Hickey (Marcel Dekker, New York, 1996) p. 337.

    Google Scholar 

  73. J. Yano, H. Furedi-Milhofer, E. Wachtel, and N. Garti, Langmuir 16 (2000) p. 10005.

    Google Scholar 

  74. A.I. Kitaigorodsky, Molecular Crystals and Molecules (Academic Press, New York, 1973).

    Google Scholar 

  75. J.W. Mullin, Crystallization (Butterworth-Heinemann, Boston, 2001).

    Google Scholar 

  76. A.Y. Lee, I.S. Lee, and A.S. Myerson, Chem. Eng. Technol. 29 (2006) p. 281.

    Google Scholar 

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  1. Alfred Y. Lee
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  2. Allan S. Myerson
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Lee, A.Y., Myerson, A.S. Particle Engineering: Fundamentals of Particle Formation and Crystal Growth. MRS Bulletin 31, 881–886 (2006). https://doi.org/10.1557/mrs2006.207

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