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Single-step recovery of ephedrine hydrochloride from raw materials using

expanded bed adsorption

Article  in  Biotechnology Letters · September 2004

DOI: 10.1023/B:BILE.0000036603.35042.70 · Source: PubMed

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 Biotechnology Letters 26: 1233–1236, 2004.
© 2004 Kluwer Academic Publishers. Printed in the Netherlands.
1233

Single-step recovery of ephedrine hydrochloride from raw materials using

expanded bed adsorption

Wei-Dong Chen, Yan-Dong Wang, Li-hang Zha, Guang-Hui Ma & Zhi-Guo Su∗
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences,
Beijing 100080, P.O. Box 353, P.R. China
∗ Author for correspondence (Fax: +86-10-62561822; E-mail: wdchen@home.ipe.ac.cn)

Received 5 May 2004; Revisions requested 6 May 2004; Revisions received 28 May 2004; Accepted 28 May 2004

Key words: cation resin, chromatography, ephedrine hydrochloride, expanded bed adsorption

Abstract
Expanded bed adsorption, using a cation resin 001 × 7 Styrene-DVB, was used to recover and purify ephedrine
hydrochloride from a powdered herb. The axial liquid-phase dispersion coefficient was about 10−5 m2 s−1 and the
recovery yield and purification reached 86% and 22, respectively. Compared with using conventional extraction
with dimethylbenzene, this method is safer and also more efficient.

Introduction Materials and methods

Since pharmacologically active compounds in herbal Materials

plants usually are in low concentrations, extraction
methods are needed for their recovery (Lang & Wai
2001, Tsai 2001, Wang et al. 2003). Ephedrine,
a traditional Chinese medicine and important phar-
maceutical, is obtained by the extracts from plants
of the genus Ephedra (Yomasaki et al. 1973, Shin
& Rogers 1996, Ren 2002, Mandwal et al. 2004).
Usually, it is used as its hydrochloride. As an adren-
aline medicine, it can prevent and even cure bronchial
asthma, resolve toxicosis of the soporific and cure
myxoedema of the nose, urticaria etc. (Tripathi et al.
1997, Herráez-Hernández & Campíns-Falcó 2001).
The classical purification method for ephedrine hy-
drochloride uses a combination of conventional infu-
sion and organic solvent extraction or adsorption (Ren
2002). In this paper, we describe the application of the
expanded bed adsorption technology, which reduces
the number of operations in purification processes
by combining clarification, concentration and capture
into one operation (Chase & Draeger 1992, Chen et al.
2003a), with the cation resin, 001 × 7 Styrene-DVB,
in the purification of ephedrine hydrochloride directly
from unclarified feedstock.
Ephedra herb was provided by Beijing Tongrentang
Pharmaceutical Co. Ltd. (Beijing, P.R. China). Cation
resin, 001 × 7 Styrene-DVB, was from Chemical Plant
of Nankai University (Tianjin, China). It is fabricated
by coupling sulfonic groups to styrene-divinylbenzene
copolymers according to the manufacturer. The ion-
exchange medium in the H+ form has a wet density of
1.25 g ml−1 , an ion-exchange capacity of 1.85 M and a
size distribution of 205 to 1030 µm. All other reagents
are of analytical grade.
Preparation of feedstock
Suspensions of pulverized Ephedra herb digested with
50 mM HCl for 50 min were buffered by 10 mM
phosphate buffer, pH 7.2, as the feedstock. The con-
centration of ephedrine hydrochloride in this feedstock
was about 1.4 mg ml−1 .
Purification of ephedrine hydrochloride
The experimental protocols were the same as those
described previously (Chen et al. 2003a). Liquid-
phase dispersion behavior in the expanded bed was
1234

determined by the residence time distribution method

as stated previously (Chen et al. 2003b).
During the whole operation process, the outlet
stream from the bed was collected every 5 to 10 ml.
The suspension in the collected pool was then cent-
rifuged at 5000 g for 10 min (to settle the powdered
herbs) and the equilibrium concentration of ephedrine
hydrochloride in the supernatant was determined by
reversed-phase HPLC with an Ultrasphere ODS C18
column (250 × 4.6 mm I.D., 5 µm) and 10 mM po-
tassium dihydrogen phosphate/methanol (90:10, v/v,
pH 2.5) as mobile phase with detection at 210 nm. The
impurity concentration was determined after dryness
as described previously (Ren 2002).

Analysis and measurements

The particle size distribution of 001 × 7 Styrene-DVB

was measured with a Coulter-LS230 particle analyzer
(Beckman Coulter, FL). The wet density of the resin
was measured by a pycnometer at 25 ◦ C.
Results and discussion
Purification of ephedrine hydrochloride by expanded
bed chromatography
Fig. 1. Chromatographic profile of ephedrine hydrochloride (♦, left
ordinate) in the expanded bed adsorption process with raw materials
as feedstock (Exp. 1). Broken line denotes the salt concentrations
of the elution buffer (right ordinate), the elution gradient of 596 ml
from 0 to 1 M NaCl in 10 m M phosphate buffer pH 7.2 was ad-
opted. C: Concentration of ephedrine hydrochloride in bulk phase,
C0 : concentration of ephedrine hydrochloride in feedstock (1.39 mg
ml−1 ). The loading step was carried out at an average flow rate of
493 cm h−1 , and the elution steps were carried out at an average
flow rate of 523 cm h−1 .

The axial liquid-phase dispersion coefficient was

measured in the order of 10−5 m2 s−1 in the pres- Table 1. Purification of ephedrine hydro-
ence of powdered herbs (data not shown), within the chloride in the presence of powdered herbs
using the expanded bed of 001 × 7
common range of 1 × 10−6 to 1 × 10−5 m2 s−1 ob- Styrene-DVB (25 ◦ C)a .
served previously (Thömmes et al. 1996, Pålsson et al.
2000). The result suggests that 001 × 7 Styrene-DVB Exp. Purityb PFc Yield Irfd
is suitable for efficient expanded bed operation in the no. (%) (%) (%)
presence of powdered herbs. 1 47.9 12.2 47 96.2
Table 1 summarizes that the yields and the puri- 2 84.9 22.3 86.3 96.1
fication factors of ephedrine hydrochloride, and the
a Expanded, a glass column (90 cm ×
impurity removal factors obtained in two experiments
16 mm I.D.) was used for all expanded
of expanded bed adsorption (Figures 1 and 2). In bed experiments. A stainless steel mesh
Exp. 1, the yield and purification factor values were of 149 µm openings was installed in the
relative low, namely 47% and 12, respectively. It column bottom as the flow distributor. All
is due to the 87% breakthrough of ephedrine hydro- expanded bed experiments were done on the
ÄKTA purifier 100 with a settled bed height
chloride in the loading stage and the linear gradient of 11 ± 0.2 cm. The loading and washing
elution protocol adopted (Figure 1). In Exp. 2, the steps were carried out at a bed expansion
yield and purification factor values reached 86% and degree of 1.3, while the elution stage was
22, respectively, because the loading was stopped at performed at a bed expansion degree of 1.1.
b Value of Purity equals to the ratio of
17% breakthrough of ephedrine hydrochloride and the ephedrine hydrochloride to impurity amount.
phosphate buffer with 1 M NaCl as the second elution c PF stands for Purification Factor of

buffer was adopted (Figure 2). The impurity removal ephedrine hydrochloride.
d IRF refers to as Impurity Removal Factor.
factor reached about 96% in both experiments (see
Table 1).

Fig. 2. Chromatographic profile of ephedrine hydrochloride in the
expanded bed adsorption process with raw materials as feedstock
(Exp. 2). Broken lines denote the salt concentrations of the elu-
tion buffers, the first elution buffer was 10 m M phosphate buffer
pH 7.2 with 0.1 M NaCl, and the second elution buffer was the phos-
phate buffer with 1 M NaCl. Symbols are the same as in Figure 1.
C0 = 1.45 mg ml−1 . The loading step was carried out at an average
flow rate of 476 cm h−1 , and the elution steps were carried out at an
average flow rate of 517 cm h−1 .
The results confirmed that the impurity adsorbed
on the adsorbent could be efficiently washed out dur-
ing washing process. In addition, it can be found (see
footnote of Table 1 and legends of Figures 1 and 2) that
the loading step was carried out at a higher expansion
degree than the elution, while the loading was done at
a lower flow rate than elution. The result shows that the
difference in flow vs. expansion degree is correlated to
viscosity of the mobile phase applied.
Comparison of expanded bed adsorption, packed bed
adsorption and traditional organic solvent extraction
A comparison was made between the adsorption ef-
ficiency in a fixed and expanded bed by examining
the adsorption of ephedrine hydrochloride to 001 × 7
Styrene-DVB in the 16 mm diam. column. In these
experiments, the adsorbate was applied to the same
amount of adsorbent at the same volumetric flow rate
with the bed in either a packed or expanded con-
figuration. When the adsorbent bed is expanded to
approximately 1.3 times its settled bed height, little
difference between the efficiency of ephedrine hy-
drochloride adsorption in the fixed or expanded bed
modes has been found (data not shown). The res-
ult is similar to those published previously in pro-
1235
tein purification (Chase & Draeger 1992, Chen et al.
2003a). The lower overall process time of expanded
bed adsorption and higher product recovery (86% for
expanded bed adsorption, and 79% for packed bed ad-
sorption) could be obtained because the expanded bed
adsorption technology provided a single-step approach
to yield ephedrine hydrochloride.
Compared with the present process used in the in-
dustry, namely traditional organic solvent extraction,
the purity of ephedrine hydrochloride (85%) reached
by the expanded bed adsorption technology equaled
to that of 4 to 6 times refine by solvent crystalliza-
tion in industry (80% to 90%), and the recovery of
ephedrine hydrochloride was increased by about 22%
(from 67% to 86%) (Ren 2002). Most importantly,
the chromatographic technology avoids the use of di-
methylbenzene, which is toxic both to the operators
and to environment.
At present, a little study of the purification of
natural products and active components of Chinese
herbal preparations using the expanded bed adsorption
technology is reported (Córdoba et al. 1996). There-
fore, the results obtained in this work provided an
insight into the recovery of natural products by expan-
ded bed adsorption technology. However, it should be
noted that the ephedrine hydrochloride solution col-
lected from the expanded bed is mainly a mixture
of L-ephedrine hydrochloride and D-pseudoephedrine
hydrochloride, so the obtained solution of ephedrine
hydrochloride should be further refined by solvent
crystallization of 1 to 2 times to obtain final products.
In a whole, as a primary step of ephedrine hydro-
chloride purification from raw materials, the expan-
ded bed adsorption technology reduces the number of
operations in purification process by combining clari-
fication, concentration and capture into one operation,
leading to the reduction of costs and processing time
and the increase of product recovery yield and quality.
The results suggest that the expanded bed adsorption
technology is promising in the separation of active nat-
ural products, such as ephedrine hydrochloride and so
on, directly from raw materials.
Acknowledgement
This work is supported by the Natural Science Found-
ation of China (Grant No. 20136020).
 1236
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