Issue
Korean Journal of Chemical Engineering,
Vol.21, No.4, 816-820, 2004
Preparation and Characterization of Paclitaxel from Plant Cell Culture
The solvent treatment of paclitaxel is a convenient method for controlling the morphologies of paclitaxel. Amorphous paclitaxel was simply made by dissolving paclitaxel in methylene chloride/methanol (98/2, v/v) and in relatively non-polar solvents (t-butyl methyl ether, pentane, acetonitrile/hexane (1/2, v/v), methylene chloride, chloroform). On the other hand, dihydrated paclitaxel (paclitaxel·2H2O) was made by dissolving paclitaxel in a special polar solvent containing a small amount of water. However, when we used only methanol, we got mixed morphologies of paclitaxel made of both the dihydrated and amorphous forms. Their physicochemical properties were investigated by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermo gravimetric analysis (TGA). The initial water content of amorphous paclitaxel and dihydrated paclitaxel was determined for 0.65 wt% and 5.85 wt%, respectively. The hygroscopic property of dihydrated paclitaxel was very changeable in all given humidity (15, 60, 95 RH%) during storage. Dissolution profiles for paclitaxel showed that amorphous paclitaxel measured the highest solubility in water and its solubility held most stable during the measurements. The residual solvent could be reduced to the maximum allowed value (600 ppm for methylene chloride, 3,000 ppm for methanol) of guidance for the International Conference on Harmonization (ICH) by spray drying.
[References]
  1. Angell CA, Monnerie L, Torell LM, Mater. Res. Soc. Symp. Proc., 215, 3, 1991
  2. Chiou WL, Riegelman S, J. Pharm. Sci., 60, 1281, 1971
  3. Choi HK, Yun JH, Kim SI, Son JS, Kim HR, Kim JH, Choi HJ, Hong SS, Enzyme Microb. Technol., 29(10), 583, 2001
  4. Gi US, Min B, Hong SS, Lee HS, Kim JH, Agric. Chem. Biotech., 43, 176, 2000
  5. Hancock BC, Shamblin SL, Zografi G, Pharm. Res., 12, 799, 1995
  6. ICH Guidance Q3C impurities: Residual Solvents, Federal Register, 62(247), 67378, 1997
  7. Kim JH, Hong SS, Korean J. Biotechnol. Bioeng., 15, 346, 2000
  8. Kim JH, Choi HK, Hong SS, Lee HS, J. Microbiol. Biotechnol., 11, 204, 2002
  9. Kim JH, Kang IS, Choi HK, Hong SS, Lee HS, Process Biochem., 37, 679, 2002
  10. Kwon IC, Yoo YJ, Lee JH, Hyun JO, Process Biochem., 33(7), 701, 1998
  11. Liggins RT, Hunter WL, Burt HM, J. Pharm. Sci., 86, 1458, 1997
  12. Martin A, Swarbrick J, Cammarata A, "Physical Pharmacy," Lea and Febiger, Philadelphia, 1983
  13. Mathew AE, Mejillano MR, Nath JP, Himes RH, Stella VJ, J. Med. Chem., 35, 145, 1992
  14. Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK, Claiborne CF, Renaud J, Couladouros EA, Paulvannan K, Sorensen EJ, Nature, 367, 640, 1994
  15. Sharma US, Baulausbramanaian SV, Straubinger RM, J. Pharm. Sci., 84, 1223, 1995
  16. Wani Mc, Taylor HL, Wall ME, Coggon P, Mcphail AT, J. Am. Chem. Soc., 93, 2325, 1971