Cost Reduction of
Solvent Recovery in
Pharmaceutical Plants
Process Gas Chromatograph MAXUM II
replaces costly Lab Analysis by on-line
Analytics
Case Study · August 2008
Use of Solvents
The pharmaceutical industry relies
on the use of large quantities of organic solvents in a great number of
manufacturing steps including
chemical synthesis, fermentation,
extraction, formulation and finishing of products. Solvents such as acetone, methyl ethyl ketone and tetrahydrofuran are commonly used as
reaction media and for extracting
products in the pharmaceutical, specialty chemicals and fragrance industries. Other solvents frequently
encountered include hexane,
dichloromethane, methanol, ethyl
acetate, toluene, xylene, triethylamine, butyl acetate and isopropanol.
Another compelling reason for recovering solvents is the increasing
environmental legislation against
emissions; such emissions may be as
a result of a process design where
solvent recovery was not incorporated at the outset, or where venting
has occurred as a result of plant
problems. With increasing commercial and regulatory pressures on
pharmaceutical industries, the recovery, reconditioning and reuse of
solvents is an important aspect of
running production facilities efficiently. Further, the FDA initiative
"Pharmaceutical Manufacturing in
the 21st Century" - with its goal of
optimizing production processes so
that quality becomes an integral element of the process - marks a crucial
turning point.
Solvent Recovery
Solvent disposal costs and VOC
emissions control have been primary concerns in the industry for some
time. For various reasons, there is an
increasing interest in recovering solvents with the direct cost saving being one of the strongest arguments.
In some processes with intensive
solvent use, the cost of the solvent
can be a significant proportion of
the overall product cost.
Process Analytics
s
Batch distillation
The most popular method of recovering
solvents is filtration and distillation. Alternatively, carbon bed absorbers are
occasionally used for filtration, and
steam is then used to desorb and recapture the solvents. The disadvantage of
this technique is that water is introduced into the recovered solvents and
this must be removed before they can
be reused. A batch distillation process is
therefore employed to purify the solvent to an acceptable level for reuse.
Clearly, there is no advantage in purifying the solvent beyond the required level as this would represent wasted resources, so analyzers such as the MAXUM II process gas chromatograph are
used to give an accurate, reliable, continuous online measurement of the
concentration of solvents.
Challenge
Use of solvents for production processes
can be expensive - expensive to purchase, expensive to store and expensive
to dispose. Further, as oil prices continue to rise, so will also costs for oil-based
solvents. Solvent recovery provides cost
savings by reductions in purchase costs
of new solvents, reductions in waste
handling costs and reductions in storage costs of both solvent and wastes.
Hence, solvent recovery processes are
increasingly used with analyzers to
monitor and optimize the processes by
providing accurate data about the actual grade of purity achieved.
A large pharmaceutical company approached Siemens with a solvent recovery application encompassing 7 different batch distillation processes as listed
in Table 1.
The analyzer requirements for this demanding analysis objective were
• Capability to serve all 7 batch processes (Table 1) with a single analyzer only
• High analytical performance regarding analysis time, choice of detectors, column technology, etc.
• High reliability in operation
2
• Seamless integration of the analyzer
into the plant production process
• Seamless integration of the analyzer
into the plants communication network
Solution
Process vs. laboratory analysis
Siemens recommended to solving this
application by means of on-line Process
Analytical Technology (PAT) instead of
laboratory analysis equipment as commonly used. Compared with laboratory
testing of samples, on-line analysis can
provide the facility with faster results,
improved accuracy, and allows trends to
be monitored in real time. On-line solvent recovery analysis is likely to reduce
the number of batches that are rejected,
saving both time and money.
Consequently, process gas chromatography is increasingly used in the Pharmaceutical Industry to measure solvent
concentrations from recovery and/or
distillation processes.
Indeed, even critical measurements of
solvent concentration levels to the ppb
range are achievable, when required.
MAXUM edition II
MAXUM edition II is a universal process gas chromatograph offering an
outstanding broad variety of analytical possibilities. Main application
field is process monitoring and control for gases and vaporable liquids in
rough industrial environments. MAXUM II performs a wide range of duties
in refineries and chemical/petrochemical industries. MAXUM II features e. g. a flexible, energy saving
single or dual oven concept, valveless sampling and column switching,
and parallel chromatography using
multiple single trains as well as a
wide range of detectors such as TCD,
FID, FPD, PDHID, PDECD and PDPID.
Important user benefits include
• Flexible range of oven capabilities
• Multiple detector and valve options
• Local panel and remote workstation
• Powerful software
• Extensive local and remote I/O’s
and serial links
• Multiple network capabilities
• Large, experienced support team
MAXUM II, the ideal solution provider
Most solvent recovery processes are
done in batches, often encompassing
several different solvents at various intervals. To be an effective solvent recovery process monitor, the gas chromatograph must accommodate this scenario.
The MAXUM II PGC (Fig. 1) does this
with ease: A single MAXUM analyzer
can accommodate several methods as
well as several hardware applications.
MAXUM provides
• Multiple detectors, multiple columns
and multiple valve arrangements
• The software capability to control
several batch methods
• The capability to communicate analysis results per batch
Thus, MAXUM is the ideal solution provider for monitoring solvent recovery
processes as shown in Fig. 2.
Fig. 1: MAXUM II Process Gas Chromatograph
Iso
Octan
e
% max
Non
Volatiles
ppm
max
Solv.
conc.
% min
H2O
% w/v
max
MeOH
% max
MeCl2
% max
Toluene
% max
Total
Alcoh.
% max
Tetrahydrofuran
(Process A)
99.0
0.05
0.02
1.0
2.0
0.05
Acetone
98.5
1.0
0.5
6.0
0.1
Dimethylformamide
99.6
0.1
0.2
20
Methylene Chloride
99.1
0.13
0.2
20
Ethyl Acetate
99.0
0.1
Tetrahydrofuran
(Process B)
99.3
0.03
Toluene
99.0
0.8
Solvent to be
Recovered
EtOH
% max
THF
% max
EtOAc
% max
20
0.1
6.0
0.5
0.7
5.0
0.3
20
0.3
20
0.25
20
0.3
20
Table 1: Specification summary of the seven solvents to be analyzed during recovery
O n e M A X U M P ro c es s G a s C h ro m a to g ra p h fo r s e ve n A p p lic a tio n s
The Siemens solution (Fig. 2) comprises:
F ID 1
C a rrie r
gas
TCD
S o lve n t re c o ve ry
p ro c ess m o n ito rin g
H 2O
A c eto n e
P reco lu m n /
B ackflu sh
S a m p le va lve s
S ep aratio n
D im eth ylfo rm am id e
M e th yle n e C h lo rid e
Is o p ro p an o l
Is o o c ta n e
A c e to n e
F ID 2
D etectio n
M eth ylen e C h lo rid e
E th yl A cetate
T etrah yd ro fu ran (A an d B )
C o lu m n va lve s
T o lu en e
Fig. 2: Dual oven analysis configuration of MAXUM for solvent recovery monitoring
R_FID
Case 3/MEA (11/29/2006 2:39:12 PM)
0.000
13
Name
ESTD concentration
Units
13
12
12
Ethyl
Acetate
11
11
10
10
Methylene
Chloride
9
9
8
8
7
7
Tetrahydrofuran
0.000
Ethanol
6
6
0.000
0.000
0.000
1
0.000
2
R_FID Flame Indicator 26.322
R_FID Flame Indicator 73.678
4
3
tetrahydrofuran 0.500 LV%
5
4
ethanol 1.000 LV%
5
3
2
1
0
0
-1
-1
0
20
40
60
80
100
120
140
160
180
200
220
240
280
260
300
320
340
Seconds
11
12
0.000
L_FID
Case 3/MEA (11/29/2006 2:39:12 PM)
12
Name
ESTD concentration
Units
11
10
10
9
9
8
8
Ethyl
Acetate
7
Methylene
Chloride
7
6
6
5
3
0.000
0.000
0.000
0.000
0.000
1
0.000
2
4
L_FID Flame Indicator 24.461
L_FID Flame Indicator 32.812
L_FID Flame Indicator 42.728
4
methylene chloride 10.000 LV%
5
0.000
Fig. 3 shows examples of the analytical
performance of MAXUM.
M e th an o l
E th a n o l
E th yl A c e ta te
T e tra h yd ro fu ra n
T o lu e ne
T o ta l alc o h ols
L e ft a irb a th o ve n
C a rrie r
gas
0.000
0.000
0.000
This configuration enables MAXUM to
measure simultaneously Methanol, Ethanol, Ethyl Acetate, Tetrahydrofuran,
Toluene, Total Alcohols (train with
FID 1), H2O (train with TCD) and Methylene Chloride, Isopropanol, Isooctane,
Acetone (train with FID 2). Consequently, the recovery processes of all 7 solvents (Fig. 2) can be monitored and
controlled with just one analyzer and
without any modification of the analyzer.
R ig h t a irb a th o ve n
0.000
0.000
0.000
• One MAXUM Process Gas Chromatograph in split airbath oven configuration
• One sample gas stream
• Three straight forward analysis trains
with sample and column switching
valves and two FIDs and one TCD.
• 7 analytical methods using EZChrom
software to handle the 7 different
batch processes
S a m p le
C a rrie r
gas
3
2
1
0
0
-1
-1
0
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
320
340
Seconds
Fig. 3: Separation of Ethyl acetate, above: FID 1, below: FID 2
3
User Benefits
Process analyzers in a Pharmaceutical
plant contribute significantly to a correct, efficient and safe plant operation.
The analyzers must be of very high performance and reliability, and their integration into the plant requires a high degree of know-how and engineering experience. Siemens has brought these attributes to industry for many years.
•
•
•
In the actual application, the end-user
found the following benefits resulted
from use of the MAXUM Process Gas
Chromatograph in their solvent recovery process:
•
Fig. 4: Typical solvent recovery plant
Compared to the conventional method
of analyzing samples off-line in the laboratory the end-user estimated a total
annual savings due to the installation of
MAXUM of above $ 200 000 (Table 2).
• Capability to monitor and control
seven different solvent recovery processes with just one single Chro-
Process
•
matograph and with-out hardware or
software modifications
Reduced costs per measurement due
to reduced lab operations
Improved process through-put due to
much faster response from on-line
process analysis compared to lab
analysis
Reduced costs by avoiding re-running of distillation processes through
critical point analysis.
Improved solvent yields through better and faster process monitoring
Reduced waste solvent with need for
disposal
Frequency
Improved process through-put
(Avoid delay waiting on lab data)
Increase number of
batch distillations by
2.0 % for same facility
Reduced costs per measurement
(Lab operations)
Per batch
Avoidance of re-run distillation by
missing cut-off point. Critical
point determination
Re-run assumed to
occur twice per
50 batches
Improved solvent yields through
better and faster process monitoring
Per batch
Reduced solvent waste for
disposal
Per batch
Per batch
Assumptions
Savings per
batch
Facility capital costs to be
$ 500K
1,5 h
Hourly lab/capital rate to
be $ 275
$ 10 000
$ 412
Single distillation costs to
be $ 15 000
Yield increase 10 % yield improvement
by 10 %
equal to 100 gallon solvent
$ 20 600
$ 30 000
100 gal solvent
~ $ 3 000
Reduced waste 10 % yield improvement
Disposal costs
solvent by 10 % equal to 100 gallon waste ~ $ 0.36 per gallon
solvent
Total Annual Costs Savings
Annual savings estimated (50 batches)
$ 150 000
$ 1 750
$ 212 350
Table 2: Savings summary
Siemens AG
Industry Sector
Sensors and Communication
Process Analytics
Östliche Rheinbrückenstr. 50
76181 KARLSRUHE
GERMANY
www.siemens.com/processanalytics
Subject to change without prior notice
© Siemens AG 2008
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