An efficient and economical low-pressure liquid chromatography process
has been developed for paclitaxel recovery and purification directly
from plant-tissue culture (PTC) broth. PTC broth is first diluted with
ethanol to ensure paclitaxel dissolution and then passed through a co
lumn packed with a high-capacity polystyrene divinyl-benzene sorbent.
A step increase in ethanol concentration in the mobile phase (ethanol:
water) is used to concentrate and compress the taxane bands to as high
as 29-fold of influent concentrations (about 1 mg/L). A recycle techn
ique is then used to separate the concentrated paclitaxel band from ot
her taxane bands, achieving 95% purity with more than 90% recovery and
99% purity with more than 80% recovery. In this process, the same low
-pressure columns are used to capture, concentrate and purify paclitax
el. Theoretical predictions agree closely with the stepwise elution an
d recycle chromatography data. After validation simulations are used t
o explore various design and operating alternatives. Analysis of the a
lternatives shows that the process cost can be further reduced by usin
g higher feed concentration, larger loading volume, smaller particle s
ize, and optimal gradient and recycle strategies.