화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.62, 436-445, June, 2018
DOI10.1016/j.jiec.2018.01.027  Export Citation
Assessment of amorphization behavior of a drug during co-grinding with an amino acid by discrete element method simulation
Akira Kitayama, Kazunori Kadota1, †, Seika Fujioka, Yuto Konishi, Hiromasa Uchiyama1, Yuichi Tozuka1, Atsuko Shimosaka, Mikio Yoshida, and Yoshiyuki Shirakawa
  • Department of Chemical Engineering and Material Science, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Japan
  • 1Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, Japan
E-mail:
The amorphization of indomethacin (IMC) with cystine (Cys2) was studied by discrete element method (DEM) simulations and principal component analysis (PCA). X-ray powder diffraction (XRPD) analysis suggested that the conversion of crystalline IMC to amorphous state was accelerated by co-grinding with Cys2. XRPD spectra about amorphization of IMC with Cys2 were analyzed by PCA. PCA results suggest that IMC/Cys2 system undergoes two-phase amorphization, as indicated by the 2nd PC score, and that the change in phase depends on the total frictional energy calculated by DEM simulations. Electron spin resonance result revealed that the radical from Cys2 may be related to the amorphized progression of IMC.
Keywords:Ball milling;Principal component analysis;Total friction energy;Discrete element method;Electron spin resonance
  1. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJH, Pharmacol. Rev., 65, 315 (2013)
  2. Dengale SJ, Grohganz H, Rades T, Lobmann K, Adv. Drug Deliv. Rev., 100, 116 (2016)
  3. Baghel S, Catchcart H, O’Reilly NJ, J. Pharm. Sci., 105, 2527 (2016)
  4. Yu L, Adv. Drug Deliv. Rev., 48, 27 (2001)
  5. Prasanthi NL, Sudhir M, Jyothi N, Srivajrapriya V, Am. J. Adv. Drug Deliv., 5, 58 (2016)
  6. Sun Y, Zhu L, Wu T, Cai T, Gunn EM, Yu L, AAPS J., 14, 380 (2012)
  7. Trasi NS, Purohit HS, Wen H, Sun DD, Taylor LS, J. Pharm. Sci., 106, 264 (2017)
  8. Huanga Y, Dai WG, Acta Pharmacol. Sin. B, 4, 18 (2014)
  9. Laitinen R, Lobmann K, Strachan CJ, Grohganz H, Rades T, Int. J. Pharm., 453, 65 (2013)
  10. Shayanfar A, Jouyban A, J. Pharm. Innov., 8, 218 (2013)
  11. Gniado K, Lobmann K, Rades T, Erxleben A, Int. J. Pharm., 504, 20 (2016)
  12. Lobmann K, Grohganz H, Laitinen R, Strachan C, Rades T, Eur. J. Pharm. Biopharm., 85, 873 (2013)
  13. Jensen KT, Larsen FH, Cornett C, Lobmann K, Grohganz H, Rades T, Mol. Pharm., 12, 2484 (2015)
  14. Lim AW, Lobmann K, Grohganz H, Rades T, Chieng N, J. Pharm. Pharmacol., 68, 36 (2016)
  15. Beyer A, Radi L, Grohganz H, Lobmann K, Rades T, Leopold CS, Eur. J. Pharm. Biopharm., 104, 72 (2016)
  16. Hu Y, Gniado K, Erxleben A, McArdle P, Cryst. Growth Des., 14, 803 (2014)
  17. Uzarevic K, Strukil V, Mottillo C, Julien P, Puskaric A, Friscic T, Halasz I, Cryst. Growth Des., 16, 2342 (2016)
  18. Jensen KT, Lobmann K, Rades T, Grohganz H, Pharmaceutics, 6, 416 (2014)
  19. Descamps M, Aumelas A, Desprez S, Willart JF, J. Non-Cryst. Solids, 407, 72 (2015)
  20. Burmeister CF, Kwade A, Chem. Soc. Rev., 42, 7660 (2013)
  21. Yong LS, Qiong-Jing M, Zheng P, Xiao-Dong L, Jian-Hua Y, Chin. Phys. B, 21, 078201 (2012)
  22. Khanal M, Jayasundara CT, Particuology, 16, 54 (2014)
  23. Feng YT, Han K, Owen DRJ, Mat. Sci. Eng., 375, 815 (2004)
  24. Cleary PW, Particuology, 8, 106 (2010)
  25. Lee H, Cho H, Kwon J, Powder Technol., 198(3), 364 (2010)
  26. Hancock BC, Zografi G, Pharm. Res., 11, 471 (1994)
  27. Moggach SA, Allan DR, Parsons S, Sawyer L, Warren JE, J. Synchrotron Radiat., 12, 598 (2005)
  28. Abdellaoui M, Gaffet E, Acta Metall. Mater., 43, 1087 (1995)
  29. Roux MV, Foces-Foces C, Notario R, da Silva MAVR, da Silva MDMC, Santos AFLOM, Juaristi E, J. Phys. Chem. B, 114(32), 10530 (2010)
  30. Chattopadhyay PP, Manna I, Talapatra S, Pabi SK, Mater. Chem. Phys., 68(1-3), 85 (2001)
  31. Mio H, Kano J, Saito F, Kaneko K, Mater. Sci. Eng. A-Struct. Mater. Prop. Microstruct. Process., 332, 75 (2002)
  32. Jensen KT, Larsen FH, Lobmann K, Rades T, Grohganz H, Eur. J. Pharm. Biopharm., 107, 32 (2016)
  33. Mio H, Kano J, Saito F, Kaneko K, Int. J. Miner. Process., 74, S85 (2004)
  34. Konishi Y, Kadota K, Tozuka Y, Shimosaka A, Shirakawa Y, Powder Technol., 301, 220 (2016)
  35. Shirakawa Y, Hayashi Y, Kadota K, Mio H, Ohtsuki H, Shimosaka A, Hidaka J, J. Nanopart. Res., 10, 577 (2008)
  36. Guzman L, Chen Y, Potter S, Khan MR, CIGR J., 17, 235 (2015)
  37. Ahn JJ, Akram K, Kwon JH, Food Anal. Methods, 5, 1196 (2012)
  38. Oughton BM, Harrison PM, Acta Crystallogr., 12, 396 (1959)
  39. Ejgenberg M, Mastai Y, Cryst. Growth Des., 12, 4995 (2012)
  40. Shtukenberg AG, Zhu Z, An Z, Bhandari M, Song P, Kahr B, Ward MD, PNAS, 110, 17195 (2013)
  41. Flores-Huerta AG, Tkatchenko A, Galvan M, J. Phys. Chem. A, 120(21), 4223 (2016)
  42. Aceves-Hernandez JM, Nicolas-Vazques I, Aceves FJ, Hinojosa-Torres J, Paz M, Castano VM, J. Pharm. Sci., 98, 2448 (2009)
  43. Chung FH, J. Appl. Crystallogr., 7, 519 (1974)
  44. Sato A, Kano J, Saito F, Adv. Powder Technol., 21(2), 212 (2010)
  45. Shimono K, Kadota K, Tozuka Y, Shimosaka A, Shirakawa Y, Hidaka J, Eur. J. Pharm. Sci., 76, 217 (2015)
  46. Wise BM, Gallagher NB, J. Process Control, 6(6), 329 (1996)
  47. Strachan CJ, Rades T, Gordon KC, J. Pharm. Pharmacol., 59, 261 (2007)
  48. Khomane KS, More PK, Raghavendra G, Bansal AK, Mol. Pharm., 10, 631 (2013)
  49. Dushkin AV, Chem. Sustain. Dev., 12, 251 (2004)
  50. Marickar YMF, Lekshmi PR, Varma L, Koshy P, Urol. Res., 37, 263 (2009)
  51. Lobmann K, Laitinen R, Strachan C, Rades T, Grohganz H, Eur. J. Pharm. Biopharm., 85, 882 (2013)
  52. Taylor LS, Zografi G, Pharm. Res., 14, 1691 (1997)
  53. Basavoju S, Bostrom D, Velaga SP, Pharm. Res., 25, 530 (2008)
  54. Carta R, Tola G, J. Chem. Eng. Data, 41(3), 414 (1996)