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Conflict of Interest: In relation to this article, we declare that there is no conflict of interest.

Publication history: Received March 4, 2004
Accepted March 31, 2004

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Preparation and Characterization of Paclitaxel from Plant Cell Culture

Un-Sook Gi^† Bumchan Min¹ Jeong Hoon Lee¹ Jin-Hyun Kim²

Samyang Genex Biotech Research Institute, Daejeon 305-348, Korea ¹Samyang Central R&D Institute, Daejeon 305-348, Korea ²Department of Chemical Engineering, Kongju National University, 182 Shinkwan-Dong, Kongju 314-701, Korea

Korean Journal of Chemical Engineering, July 2004, 21(4), 816-820(5), 10.1007/BF02705526

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Abstract

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.

Keywords

Amorphous Paclitaxel Dihydrated Paclitaxel X-ray Powder Diffraction Thermo Gravimetric Analysis Physicochemical Property Spray Drying

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