화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Korean Journal of Chemical Engineering, Vol.38, No.11, 2304-2312, November, 2021
DOI10.1007/s11814-021-0891-4  Export Citation
Solubility measurement and preparation of nanoparticles of ampicillin using subcritical water precipitation method
Hadi Share Mohammadi, Ali Haghighi Asl†, and Maryam Khajenoori
  • Faculty of Chemical, Petroleum and Gas Engineering, Semnan University, Semnan 35131-19111, Iran
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To improve the bioavailability of ampicillin trihydrate (AMP) as a poorly water-soluble drug, the nanonization of AMP particles was carried out by solvent anti-solvent precipitation for the first time. In this method the subcritical water (SW) and cold water at ambient conditions were utilized as the solvent and anti-solvent, respectively. At first, the solubility of AMP in SW was measured. The solubility of AMP in SW at a constant pressure of 5MPa and the temperature range from 303.15 to 403.15 K was found to range from 0.380 x10-3 to 17.689 x 10 -3 mole fractions. The effects of three independent variables, including SW temperature, polyethylene glycol concentration, and anti-solvent temperature, on the particle size and morphology of the precipitated nanoparticles were studied. The obtained results of analyses confirmed that the AMP particles were nanosized to the smallest mean size of 66.5 nm using an environmentally friendly method without the requirement of organic solvents and related post-processing purification stages.
Keywords:Ampicillin Trihydrate;Subcritical Water;Solubility;Bioavailability;Nanoparticles
  1. Absalan G, Abbaspour A, Jafari M, Nekoeinia M, Ershadifar H, J. Iran. Chem. Soc., 12, 879 (2015)
  2. Tenorio A, Gordillo MD, Pereyra C, de la Ossa EJM, J. Supercrit. Fluids, 40(2), 308 (2007)
  3. Reverchon E, Porta GD, Spada A, J. Pharm. Pharmacol., 55, 1465 (2003)
  4. Sharma SK, Singh L, Singh S, Sch. J. Appl. Med. Sci., 1, 291 (2013)
  5. Fan Y, Pauer AC, Gonzales AA, Fenniri H, nt. J. Nanomedicine, 14, 7281 (2019)
  6. Poole JW, Bahal CK, J. Pharm. Sci., 57, 1945 (1968)
  7. Wu Y, Loper A, Landis E, Hettrick L, Novak L, Lynn K, Chen C, Thompson K, Higgins R, Batra U, Int. J. Pharm., 285, 135 (2004)
  8. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, Cho JM, Yun G, Lee J, Asian J. Pharm. Sci., 9, 304 (2014)
  9. Pu Y, Wang JX, Wang D, Foster NR, Chen JF, Chem. Eng. Process., 140, 36 (2019)
  10. Sodeifian G, Razmimanesh F, Sajadian SA, J. Mol. Liq., 297, 11740 (2020)
  11. Sodeifian G, Sajadian SA, Ardestani NS, Razmimanesh F, J. Supercrit. Fluids, 147, 241 (2019)
  12. Sayyar Z, Jafarizadeh-Malmiri H, Chem. Eng. Process, 153, 107938 (2020)
  13. Quan C, Carlfors J, Turner C, Chin. J. Chem. Eng., 17(2), 344 (2009)
  14. Kayser O, Lemke A, Hernandez-Trejo N, Curr. Pharm. Biotechnol., 6, 3 (2005)
  15. Leuner C, Dressman J, Eur. J. Pharm. Biopharm., 50, 47 (2000)
  16. Stolnik S, Illum L, Davis S, Adv. Drug Deliv. Rev., 16, 195 (1995)
  17. Keck CK, Muller RH, Eur. J. Pharm. Biopharm., 62, 3 (2006)
  18. Louey MD, Oort MV, Hickey AJ, Pharm. Res., 21, 1200 (2004)
  19. Rasenack N, Steckel H, Muller BW, J. Pharm. Sci., 92, 35 (2003)
  20. Song KH, Lee CH, Lim JS, Lee YW, Korean J. Chem. Eng., 19(1), 139 (2002)
  21. Chinnarasu C, Montes A, Pereyra C, Casas L, Fernandez-Ponce MT, Mantell C, Pattabhi S, de la Ossa EM, Korean J. Chem. Eng., 33(2), 594 (2016)
  22. Park SJ, Yeo SD, Korean J. Chem. Eng., 25(3), 575 (2008)
  23. Kim CK, Lee BC, Lee YW, Kim HS, Korean J. Chem. Eng., 26(4), 1125 (2009)
  24. Dalvi SV, Mukhopadhyay M, Powder Technol., 195(3), 190 (2009)
  25. Masoodiyeh F, Karimi-Sabet J, Khanchi AR, Mozdianfard MR, Powder Technol., 269, 461 (2015)
  26. Montes A, Tenorio A, Gordillo MD, Pereyra CM, de la Ossa EJM, Ind. Eng. Chem. Res., 50(4), 2343 (2011)
  27. Esfandiari N, Ghoreishi SM, AAPS Pharm. Sci. Tech., 6, 1263 (2015)
  28. Khajenoori M, Asl AH, Hormozi F, Chin. J. Chem. Eng., 17(3), 359 (2009)
  29. Ahmadi O, Jafarizadeh-Malmiri H, Food Sci. Biotechnol., 29, 783 (2020)
  30. Alenezi R, Leeke GA, Santos RCD, Khan AR, Chem. Eng. Res. Des., 87(6A), 867 (2009)
  31. Fernandez-Prini RJ, et al., High-temperature aqueous solutions: Thermodynamic properties, CRC Press, Boca Raton (1992).
  32. Park JN, Ali-Nehari A, Woo HC, Chun BS, Korean J. Chem. Eng., 29(11), 1604 (2012)
  33. Carr AG, Mammucari R, Foster NR, Ind. Eng. Chem. Res., 49(7), 3403 (2010)
  34. Mohammadi HS, Asl AH, Khajenoori M, Chin. J. Chem. Eng., 8, 2620 (2020)
  35. Chen XY, Shang YL, Li YH, Wang JX, Maimouna AG, Li YX, Zou D, Foster NR, Yun J, Pu Y, Chem. Eng. J., 263, 20 (2015)
  36. Hugger ED, Novak L, Burton PS, Audus KL, Borchardt RT, J. Pharm. Sci., 91, 1991 (2002)
  37. Rahimi M, Valeh-e-Sheyda P, Rashidi H, Korean J. Chem. Eng., 34(11), 3017 (2017)
  38. Carr AG, Mammucari R, Foster NR, Ind. Eng. Chem. Res., 49(19), 9385 (2010)
  39. Pu Y, Lu JD, Wang D, Cai FH, Wang JX, Foster NR, Chen JF, Powder Technol., 321, 197 (2017)
  40. Carr AG, Mammucari R, Foster NR, Chem. Eng. J., 172(1), 1 (2011)
  41. Kayan B, Yang Y, Lindquist EJ, Gizir AM, J. Chem. Eng. Data, 55(6), 2229 (2010)
  42. Kapalavavi B, Ankney J, Baucom M, Yang Y, J. Chem. Eng. Data, 59(3), 912 (2014)
  43. Uematsu M, Frank EU, J. Phys. Chem. Ref. Data, 9, 1291 (1980)
  44. Caffarena ER, Grigera JR, Physica A, 342, 34 (2004)
  45. Takebayashi Y, Sue K, Yoda S, Hakuta Y, Furuya T, J. Chem. Eng. Data, 57(6), 1810 (2012)
  46. Shinoda K, J. Phys. Chem. A, 81, 1300 (1977)
  47. Miller DJ, Hawthorne SB, Anal. Chem., 70, 1618 (1998)
  48. Akay S, Kayan B, Cunbin D, Wang J, Yang Y, J. Mol. Liq., 253, 270 (2018)
  49. Karthika S, Radhakrishnan T, Kalaichelvi P, Cryst. Growth Des., 16, 6663 (2016)
  50. Turk M, J. Supercrit. Fluids, 18(3), 169 (2000)
  51. Sodeifian G, Sajadian SA, Daneshyan S, J. Supercrit. Fluids, 140, 72 (2018)
  52. Pu Y, Li YH, Wang D, Foster NR, Wang JX, Chen JF, Powder Technol., 308, 200 (2017)
  53. Pu Y, Wen XF, Li YH, Wang D, Foster NR, Chen JF, Powder Technol., 305, 125 (2017)
  54. Carr AG, Mammucari R, Foster NR, Int. J. Pharm., 405, 169 (2011)