IE83755B1 - A process for removing trace solvent from a material - Google Patents
A process for removing trace solvent from a material Download PDFInfo
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- IE83755B1 IE83755B1 IE2000/1040A IE20001040A IE83755B1 IE 83755 B1 IE83755 B1 IE 83755B1 IE 2000/1040 A IE2000/1040 A IE 2000/1040A IE 20001040 A IE20001040 A IE 20001040A IE 83755 B1 IE83755 B1 IE 83755B1
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- IE
- Ireland
- Prior art keywords
- product
- dryer
- water
- tray
- water vapour
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 30
- 239000000463 material Substances 0.000 title claims description 16
- 239000002904 solvent Substances 0.000 title claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- FIAFUQMPZJWCLV-UHFFFAOYSA-N Suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 claims description 21
- 229960005314 Suramin Drugs 0.000 claims description 21
- 238000001035 drying Methods 0.000 claims description 17
- 239000002510 pyrogen Substances 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 238000011068 load Methods 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000000047 product Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- UCPYLLCMEDAXFR-UHFFFAOYSA-N Triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 235000012970 cakes Nutrition 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000005712 crystallization Effects 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000003801 milling Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 206010000565 Acquired immunodeficiency syndrome Diseases 0.000 description 1
- 208000006673 Asthma Diseases 0.000 description 1
- 206010003816 Autoimmune disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010011401 Crohn's disease Diseases 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N Estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960001842 Estramustine Drugs 0.000 description 1
- 206010024324 Leukaemias Diseases 0.000 description 1
- 239000004698 Polyethylene (PE) Substances 0.000 description 1
- 208000005987 Polymyositis Diseases 0.000 description 1
- 206010039073 Rheumatoid arthritis Diseases 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- 206010040767 Sjogren's syndrome Diseases 0.000 description 1
- GCLGEJMYGQKIIW-UHFFFAOYSA-H Sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
- 238000010793 Steam injection (oil industry) Methods 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 229930013930 alkaloids Natural products 0.000 description 1
- 201000005794 allergic hypersensitivity disease Diseases 0.000 description 1
- 230000003466 anti-cipated Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000875 corresponding Effects 0.000 description 1
- 238000005202 decontamination Methods 0.000 description 1
- 230000003588 decontaminative Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 230000002757 inflammatory Effects 0.000 description 1
- 200000000023 metastatic cancer Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 230000002195 synergetic Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 201000006704 ulcerative colitis Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Description
“A process for removing trace solvent from a material”
Introduction
The invention relates to a factory scale process for removing trace solvent from a
material, especially a hygroscopic material. In particular the invention relates to an
improved process for producing suramin. the hexasodium salt of a polysulfonated
naphthylurea, 8,8'—[carbonylbis[imino—3,1—phenylene— carbonylimino(4—methyl—3,l—
phenylene) carbonyl—imino]] bis—1,3,5—naphthalenetrisulfonic acid.
Suramin has been utilised clinically since the 1920s as an antiparasitic agent. and
more recently has been shown to be active in the treatment of metastatic cancer;
Stein et al., J.Clin. Oncology 1989;7(4):499—508. United States Patent numbers
,767,110 and 5,597,830 describe the synergistic effect of suramin in combination
with a vinca alkaloid or estramustine for treating cancer.
In addition suramin can be used for treating autoimmune and allergic diseases such
as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, glomerular nephrites,
systemic lupus erythematosus, polymyositis, Sjogren’s syndrome, asthma and other
inflammatory alveolar diseases. Suramin can also be used for treating AIDS and
human T cell leukaemia virus.
The process for producing suramin is well known, GB 224,849, however it was
unexpectedly found that on scale up to a commercial factory scale the drying regime
of the final product was slow and difficult to optimise so as to obtain the desired
finished product. It was found that unacceptable levels of reaction solvents were
present in the final product. Similar problems arise in drying other materials,
especially hygroscopic materials.
The object of the present invention is therefore to provide an improved process for
removing trace solvents from a material, especially a hygroscopic material on a
factory scale which routinely and consistently produces material of a high quality.
Statements of Invention
According to the invention there is provided a factory scale process that removes
trace solvent from a hygroscopic material comprising the steps of:—
drying an isolated product in a dryer to remove free solvent;
rewetting the product with water; and
redrying the product to remove residual solvent to the required level.
The process of the invention facilitates the factory scale production of dried product
with a very low level of residual solvent. Intermediate milling of the product is not
required and drying time is much reduced.
Preferably the product is rewetted with water vapour. Ideally the added water or
water vapour is generated from pyrogen controlled deionised water.
In one embodiment of the invention the product is heated to facilitate the rewetting
process.
In one embodiment of the invention the product is dried in a vacuum agitated pan
dryer. In this case preferably the product is rewetted by injecting water vapour into
the pan dryer. In a preferred embodiment the process includes the step of
intermittently stopping the injection of water vapour into the pan dryer and agitating
and sampling the product before recommencing the injection of water vapour.
_ 3 -
Ideally the water vapour is injected into the pan dryer using an inert carrier such as
nitrogen gas.
In another embodiment the product is dried in a tray dryer. In this case the process
includes the steps of :-
loading at least one tray containing product into the tray dryer;
loading at least one other tray containing water into the tray dryer; and
heating the water in the dryer to rewet the product.
Preferably the tray dryer includes a number of dryer cells and a tray containing
product and a tray containing water are loaded into a dryer cell. In a preferred
embodiment the process includes the steps of removing the water tray prior to drying
of the product.
The invention is particularly applicable to hygroscopic materials such as suramin.
The term hygroscopic refers to a product which takes up at least some water. for
example by absorption.
The invention also provides for a product whenever produced by a process of the
invention. A further embodiment provides suramin whenever produced by a process
of the invention.
Detailed Description
Suramin has the following chemical structure:
O NH SO3Na H
\ N210 3 NH O
/
SO3Na
S 3Na \
SO3Na
S 3N3
It is a white or slightly pink or cream—coloured powder. It has a slightly bitter taste.
It is hygroscopic and is freely soluble in water and in physiological saline.
Suramin is produced from 8—[3—(3-aminobenzamido)—4-methylbenzamido]-l,3,5—
napthalenetrisulfonic acid sodium salt in the presence of bistrichloromethylcarbonate
(BTCMC)(Triphosgene) and sodium hydroxide as shown in the following reaction
scheme.
“3 WCW,
O SO3Na BTCMC O NH SO3Na H H
\ NaOH \
SO3H SO3Na
S 3Na 8 3N8
Typical methods for drying the final product involve drying under vacuum for up to
SO3Na
SO3Na
days. During the drying procedure the drying is interrupted and the product is
milled and sieved before recommencing drying. However it was found that when
this process was scaled up to a commercial factory scale the process resulted in a
product with high levels of reaction solvents, such as methanol, still present.
The invention provides an improved drying regime using a vacuum agitated pan
dryer or tray dryer. The initial drying procedure reduces the methanol content to 0.3
to 0.8%. The product is then rewetted by passing a stream of steam through the
headspace of the dryer. When the water content of the product has increased
sufficiently, to 10-15%, rewetting is stopped and the product is redried under
Vacuum at 80°C until dry. This procedure allows high quality suramin with a water
content of less than 10% and a methanol content of less than 0.1% to be produced on
a consistent basis. Intermediate milling of the material is not necessary and the
drying time is much reduced.
The invention will be more clearly understood from the following description given
by way of example.
Example 1: Preparation of crude suramin
l42kg 8-[3—(3—aminobenzamido)—4—methylbenzamido]—1,3,5—napthalenetrisulfonic
acid sodium salt prepared by known methods and 1150 litres water are charged to a
reaction vessel and agitated for approximately 10 minutes until the solution is
dissolved. ZN hydrochloric acid (71kg concentrated hydrochloric acid in 284 litres
water) is charged to the reaction vessel until the pH is in the range 3.8-4.0.
A solution of 17kg triphosgene and 62kg toluene are charged to the reaction vessel
over approximately 2 hours. The pH is maintained at 3.5-4.0 by charging as required
with a solution of 2N sodium hydroxide (2l.3kg sodium hydroxide in 264kg water)
and the temperature maintained at 20—30°C. After agitation for at least 1 hour 206kg
toluene is added to the reaction vessel and the contents agitated at 70rprn for 15
minutes. The contents are allowed to settle and the lower rich aqueous layer is
transferred to another vessel. A number of toluene washes of the rich aqueous layer
are carried out to remove residual phosgene and all the waste toluene streams are
combined for decontamination before disposal. The pH of the rich aqueous layer is
adjusted to 6.0 to 6.5 with 2N sodium hydroxide and the contents agitated for 15
minutes. A full vacuum is applied to the vessel and the contents distilled at 60"C
until 234-248 litres remain. The pH is adjusted to 6.0-6.5 using 2N sodium
hydroxide. The contents are then heated to 60—70°C and l005kg filtered methanol is
added. The contents are polish filtered through a single plate, a multiplate sparkler
and multi element cartridge filter.
After filtration, the filtrate is cooled to 34-36°C and agitated at 50—90rpm and further
cooled at about 1°C/10mins until crystallisation commences. While cooling. the
contents are seeded with 10g aliquots of suramin seeds. When crystallisation begins
the contents are agitated for 8 hours without temperature regulation. After 8 hours
the contents are agitated at 15—20°C for at least 6 hours, the contents are further
cooled to —2 to +2°C and agitated for at least 3 hours. The crude suramin product is
centrifuged and discharged to polyethylene lined bins.
Example 2: Preparation of pure suramin
Wet crude suramin as prepared in Example 1 (corresponding to 138.7 kg estimated
dried weight) is charged to a reaction vessel followed by 39 litres pyrogen controlled
deionised water and 256.5kg filtered methanol. The contents are agitated at 50—60“C
until in solution. The solution is cooled to 55°C and polish filtered as described in
Example 1. The solution is further cooled to 35°C, agitation is reduced to 50-90rpm
and the solution cooled at 1°C/1 Ominutes. The solution is seeded with suramin seeds
until crystallisation begins. The contents are agitated for at least 8 hours without
temperature regulation. After 8 hours the contents are cooled to 15—20°C and held at
this temperature for at least 6 hours. The solution is then cooled to +2"C for at
least 3 hours. The pure suramin product is then isolated on a centrifuge and dried.
Example 3 — Drying suramin
Method A (pan dryer:
The wet cake product from Example 2 is loaded into a stainless steel agitated
jacketed vacuum pan dryer (Guedo mixed dryer type 2500). Slow continuous
agitation at 10rpm is begun, the jacket temperature is increased to 55—65°C and the
product dried for 6 hours. The jacket temperature is then increased to 75—85°C with
full vacuum until a water content of less than 9% is achieved.
The temperature of the dryer jacket is adjusted to 70°C. Filtered steam prepared
from pyrogen controlled water is injected into the dryer using nitrogen gas as a
carrier. The steam injection is stopped and the product agitated for 5 to 10 minutes
before sampling. Steaming is then continued until a water content of more than than
% but less than 15% is achieved. Vacuum drying is recommenced and the product
is dried at 75 to 85°C until the water content is less than 10% and a methanol content
of less than 0.1% is achieved. The product is discharged and packed in moisture
resistant bags. The drying time usually takes less than 2 days.
Method B (tray dryer!
The wet cake product from Example 2 is loaded onto trays in a stainless steel tray
dryer (William Boulton Model C3) by evenly spreading the product on the trays.
The product is dried at a jacket temperature of approximately 35—45°C with full
vacuum for a minimum of 12 hours. The jacket temperature is increased to 45—75°C
and the product dried for a minimum of 6 hours until a water content of less than 9%
is achieved.
One tray of product along with a tray of pyrogen controlled deionised water is loaded
into each of the dryer cells. The dryer is heated to 70 °C until the water content in
the cake is between 10 and 15%. The water trays are then removed and the product
trays heated to 80°C and dried under vacuum until a water content of less than 10%
and 21 methanol content of less than 0.1% is achieved. The product is discharged and
packed in moisture resistant bags.
While the invention has been described with reference to the factory scale production
of suramin, it is anticipated that it will also be applicable to other materials.
especially hygroscopic materials.
The invention is not limited to the embodiments hereinbefore described which may
be varied in detail.
Claims (7)
1. A factory scale process that removes trace solvent from a hygroscopic material comprising the steps of:— drying an isolated product in a dryer to remove free solvent; rewetting the product with water; and redrying the product to remove residual solvent to the required level.
2. A process as claimed in claim 1 wherein the product is rewetted with water vapour.
3. A process as claimed in claim 1 or 2 wherein the added water or water vapour is generated from pyrogen controlled deionised water.
4. A process as claimed in any of claims 1 to 3 wherein the added water or water vapour is generated in the same chamber as the product being dried.
5. A process as claimed in any preceding claim wherein the product is dried in a vacuum agitated pan dryer.
6. A process as claimed in any of claims 1 to 3 and 5 wherein the product is rewetted by injecting water vapour into the pan dryer.
7. A process as claimed in claim 6 including the step of intennittently stopping the injection of water vapour into the pan dryer and agitating and sampling the product before recommencing the injection of water vapour. A process as claimed in claim 6 or 7 wherein the water vapour is injected into the pan dryer using an inert carrier. A process as claimed in any of claims 1 to 4 wherein the product is dried in a tray dryer. A process as claimed in claim 8 including the steps of:- loading at least one tray containing product into the tray dryer; loading at least one other tray containing water into the tray dryer; and heating the water in the dryer to rewet the product. A process as claimed in claim 10 wherein the tray dryer includes a number of dryer cells and a tray containing product and a tray containing water are loaded into a dryer cell. A process as claimed in claim 10 or 11 including the step of removing the water tray prior to drying of the product. A process as claimed in any preceding claim wherein the material is suramin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE2000/1040A IE83755B1 (en) | 2000-12-18 | A process for removing trace solvent from a material |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IEIRELAND17/12/19991999/1060 | |||
| IE991060 | 1999-12-17 | ||
| IE2000/1040A IE83755B1 (en) | 2000-12-18 | A process for removing trace solvent from a material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE20001040A1 IE20001040A1 (en) | 2002-02-06 |
| IE83755B1 true IE83755B1 (en) | 2005-01-12 |
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