药品精干包工序操作标准.docx
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药品精干包工序操作标准
1 目的PURPOSE
本标准规定了布洛芬精干包的生产操作方法、重点操作和异常现象处理、技术指标核算方法。
This standard prescribes the operation for the ibuprofen refining, drying, packaging stage, the critical operations for ibuprofen refining, drying, packaging stage and treatment of abnormal conditions.
2 范围SCOPE
本标准适用于布洛芬产品精干包操作。
This standard is applicable the operation for the ibuprofen refining, drying, packaging stage.
3 职责RESPONSIBILITY
3.1 QA负责监督本规程的执行。
QA is responsibility of supervising of the execution of this standard operation procedure.
3.2 生产运行部:
负责检查本规程技术操作的执行情况。
Manufacturing operation department:
Check the execution of this standard operation procedure.
3.3 操作人员:
负责本规程的执行和记录。
Operator:
Execute this standard operation procedure.
4 定义DEFINATIONS
4.1 N/A – 不适用Not applicable
4.2 L – 升Liter
4.3 Kg – 千克Kilogram
5 参考资料REFERENCES
N/A
起草人:
Prepared by:
部门
Title:
日期
Date:
审核人
Reviewed by:
部门
Title:
日期
Date:
批准人
Approved by:
部门
Title:
日期
Date:
颁发部门
Issued by:
分发范围
Distributive scope:
6 操作规程OPERATION PROCEDURE
6.1 溶解脱色Dissolve and decolorization
6.1.1 原料配比Material Ratio
物料名称
Material Name
纯量比
Weight Ratio
备注
Comment
布洛芬粗品
Crude Ibuprofen
1.000kg
一批粗品,和不超过70kg的回收布洛芬(II)或筛上物。
Total batch crude ibuprofen and no more than 70 kg of recovered ibuprofen (II) or oversize product.
82%乙醇
82% Ethanol
1.430+0.800L
其中1.430L为溶解布洛芬粗品用,0.800为冲洗过滤器用。
In which, 1.430L is used for dissolving, and 0.800 for washing carbon.
40%乙醇
40% Ethanol
1.120L
活性炭
Activated Carbon
0.025kg
磷酸
Phosphoric Acid
0.6ml
实际投料量的分度为10ml
The division valve of the actual charging amount should be 10ml.
6.1.2 备料Materials Preparation
6.1.2.1 备完整一批粗品,备纯量不超过70Kg的布洛芬回收品Ⅱ和成品筛上物(注:
成品筛上物的含量按100%计)。
Prepare a batch of crude Ibuprofen, Prepare no more than net weight of 70Kg recovered IbuprofenⅡ and oversize product for each final product batch.(Remark:
The assay of the oversize product will be considered as 100%).
6.1.2.2 复查82%和40%乙醇的含量,应分别在20 0C的含量为82±1 %和40±1%。
Verify the concentration of the 82% and 40% ethanol, and the concentration should be 82±1 % and 40±1% at 20 0C.
6.1.3 投料Changing Material
6.1.3.1 目视粗品溶解罐内洁净、无异物。
开进乙醇阀门,启动泵(P241),从乙醇配制罐将配量的82%乙醇泵入粗品溶解罐。
Verify the dissolving tank for crude ibuprofen is clean, and open the valve for changing ethanol, activate the pump P241, and pump the prepared 82% ethanol to the tank from diluted ethanol tank.
6.1.3.2 投入配量的粗品、回收品或筛上物、磷酸、活性炭,上好罐盖。
Change the prepared crude Ibuprofen, recovered ibuprofen, activated carbon and phosphoric acid into the dissolving tank and fasten the tank cover well.
6.1.4 溶解脱色Dissolution and Decoloration
开溶解罐回流冷凝器降温水阀,开蒸汽阀,升温,当粗品基本溶解后,开搅拌。
保持溶解罐温度60~62℃脱色30~40分钟。
Turn on the valves for cooling water on the condenser, and the steam valve on dissolving tank, increase the temperature, when the most crude Ibuprofen is dissolving in the tank, active the agitator. Maintenance the temperature at 60~62℃ for decoloration for 30 to 40 minutes.
6.1.5 稀乙醇降温Cooling the 40% ethanol
目视结晶罐内洁净,无异物,复查结晶罐罐底阀关,开进40%乙醇阀,启动泵P241,从40%乙醇配制罐向结晶罐泵入配量的稀乙醇。
开结晶罐搅拌,开夹套低温盐水进出阀,降温至-5~-10℃。
加入200~400 g 晶种。
Verify the crystallization tank is clean, and the bottom valve for changing is closed, then open the inlet valve for 40% ethanol, and active the pump P241 and pump the prepared 40% ethanol, open the agitator and the valves for chilled brine, to cool the ethanol to -5~-10℃, then add 200~400 g of seed crystal into the crystallization tank.
6.1.6 压滤Press Filtering
6.1.6.1 开循环管路阀[含溶解罐出料阀(R201B2 )、一级压滤器进出料阀(F205A1,F205B2 和 F205B3 )、打料泵阀(P204A1 和 P204B1)、溶解罐循环进料阀(R201A2 )],关去二级过滤器阀(F206A1)和(F205B1),开泵(P204),当一级压滤器充满后,关(F205B2),开(F205B1),循环打料5分钟,观察滤液澄清。
Turn on valves of the circulating pipelines [including(R201B2 ) and (F205A1,F205B2 and F205B3 ) and(P204A1 and P204B1)and (R201A2 ) ].Turn off valves (F206A1) and (F205B1) . Activate the circulating pump(P204) ,after the first level filter is filled, close the valve(F205B2),and open the valve (F205B1),circulate the material for 5 minutes and inspect the clarity of the liquid.
6.1.6.2 如果发现滤器漏炭,检查并更换过滤板。
If any carbon is leaking, check and renew the filter board.
6.1.6.3 关溶解罐循环进料阀(F205B3 and R201A2),检查阀门,通知结晶岗位检查阀门,开去二级过滤器阀(F206A1),通过两级压滤器向滤液接受罐打料。
打完料后停泵(P204),关滤液接受罐进料阀(V208A2)。
检查阀门,启动泵(P241),将配量的冲炭乙醇打入粗品溶解罐,打完后停泵(P241)。
检查阀门,启动泵(P204),将粗品溶解罐内乙醇经压滤器打入冲炭乙醇接受罐,打完后停泵(P204)。
检查阀门,开氮气阀(R201C2),用氮气将管路中料液吹到冲碳乙醇接受罐和滤液接受罐内。
Close valves(F205B3 and R201A2) of the circulating filter system, Verify valving , inform crystallization post to verify valving, Open the valve(F206A1) to the second filter , ,transfer the filtrate to the filtrate receiver through two level filters. Turn off the pump(P204) and shut the inlet valve(V208A2) when this step is finished. Verify valving, activate pump(P241), Input the charging alcohol for washing carbon into the dissolving tank for crude ibuprofen. Then turn off the pump (P241).Verify valving , activate the pump (P204), transfer the alcohol from the dissolving tank into the alcohol receiver through two level filters, then turn off the pump(P204).Verify valving, open the valve (R201C2), blow the material in pipes into alcohol receiver and filtrate receiver.
6.2 结晶Crystallization
6.2.1 滤液降温Cooling the Filtrate
6.2.1.1 开滤液接受罐搅拌,开夹层低温水阀,将滤液降温至35℃,关低温水阀,自然降温至32~33℃ 。
Activate the agitator of the filtrate receiver, open cooling water valves of cooling water, drop the temperature of the filtrate to 35 ℃ , then close the cooling water valves, allow dropping temperature naturally till 32-33 0C。
6.2.1.2 开冲炭醇罐搅拌,开夹层低温水阀,将冲炭醇降温至32℃,关降温水,自然降温至28~30℃。
Activate the agitator in the ethanol receiver for washing activated charcoal, Turn on cooling water in the jacket. Drop the temperature of the ethanol for washing activated charcoal to32℃, close the cooling water, let the temperature to 28-30 0C naturally.
6.2.2 结晶Crystallization
6.2.2.1 检查结晶罐内40%乙醇温度在 -5~-10℃。
Verify the temperature of the 40% ethanol in the crystallization tank is -5~-10℃.
6.2.2.2 检查阀门,启动滤液打料泵(P209),将32~33℃的滤液泵入结晶罐,析出结晶后,关结晶罐进料阀(R212A2)。
2~5分钟后,开结晶罐进料阀,将剩余的滤液全部加入结晶罐(加完滤液后料温16~20℃)。
加完后,停泵(P209),关滤液罐罐底阀(V208B1)。
Verify valving, activate the pump (P209), and pump the filtrate into the crystallization tank. Close the inlet valve (R212A2) of the crystallization tank, as soon as there is any crystals form the crystallization tank. After 2-5 minutes, open the inlet valve (R212A2) of the crystallization tank, continue to input the rest of the filtrate to the crystallization tank (the filtrate temperature should be 16~20℃ after finish input filtrate) .Turn off the pump (P209), close the valve (V208B1) on the bottom of the filtrate receiver.
6.2.2.3 加完滤液后,开冲炭醇罐罐底阀,启动泵(P211),将25~30℃的冲炭乙醇泵入滤液接受罐。
停泵(P211),关冲炭醇罐罐底阀(V210B1),关滤液接受罐进料阀(V208A1)。
开滤液接受罐罐底阀(V208B1),启动泵(P209),将冲炭乙醇泵入结晶罐。
停泵(P209), 关结晶罐冰盐水进出阀(R212C1 和 R212D1),开压回盐水阀(R212D2),开压缩空气阀(R212C3),压回夹层中的盐水,关压缩空气阀(R212C3),关压回盐水阀(R212D2)。
Then open the valve(V210B1) on the bottom of the alcohol receiver, activate the pump(P211), pump the ethanol which is 25~30℃for washing carbon into the filtrate receiver. Turn off the pump (P211), close the valve (V210B1) on the bottom of the alcohol receiver and close the inlet valve (V208A1) of the filtrate receiver. Open the valve (V208B1) on the bottom of the filtrate receiver, activate the pump (P209), and pump the ethanol for washing carbon into the crystallization tank. Turn off the pump(P209) ,close the chilled brine valves(R212C1 and R212D1), open the valve(R212D2) for returning chilled brine, open the compressed air valve(R212C3) ,press back the chilled brine from the jacket, close the compress air valve(R212C3) and the valve(R212D2) for returning chilled brine .
6.2.2.4 检查阀门,开热水泵(P232),在结晶罐夹套内通60~65℃热水,将结晶罐快速升温至21℃(半小时内),关热水泵(P232),自然升温至24℃, 保持24~25℃40~60分钟,关热水进、出阀(R212C2 and R212D4),开压回热水阀(R212D3),开压缩空气阀(R212C3),压回热水,关压缩空气阀(R212C3),关压回热水阀(R212D3)。
断续开、关夹层冰盐水出、进水阀(R212D1 and R212C1),缓慢(1.5~2小时)降温至22℃,开大冰盐水进、出阀(R212C1 and R212D1),降温至-2℃后,保持-2℃~-4℃结晶4小时,关冰盐水进出阀(R212C1 and R212D1),准备离心。
Verify valving, turn on the hot water pump(P232) to introduce hot water at 60-65 0C into the jacket of the crystallization tank to raise temperature rapidly to 210C (within 30 minutes), then turn off the hot water pump(P232) , let the temperature rise slowly to 240C then keep the temperature at 24~25℃ for 40~60 minutes .Close the inlet and outlet valves(R212C2 and R212D4) of the hot water , open the return valve(R212D3) of hot water, open the compress air valve(R212C3) ,press back the hot water in the jacket, close the compress air valve(R212C3), close the return valve(R212D3) of hot water. .Open spasmodically chilled brine valves(R212D1 and R212C1), drop the temperature to 22 0C slowly(1.5~2hours) Then open largely the inlet and outlet valves(R212C1 and R212D1), drop the temperature to -2 0C . Keep the temperature at -2℃~-4℃, crystal for 4 hours. Then turn off the inlet and outlet valves(R212C1 and R212D1) of chilled brine. Be ready for centrifugation.
6.2.3 重点操作和异常处理Critical operations and treatment of abnormal conditions
6.2.3.1 滤液温度控制在32~33℃加入结晶罐。
Maintain the temperature of the filtrate at 32~33℃ when adding them into crystallization tank.
6.2.3.2 降温水及热水切换时注意各阀门开关正确。
Pay attention to open or close the valves correctly when switch the hot water and the ice brine.
6.3 离心Centrifugation
6.3.1 准备工作Preparation
6.3.1.1 检查离心机滤包清洁无破损,检查料车清洁无异物。
Inspect the centrifuge and filter bags to assure they are clean and with no leak, inspect the skip car to assure they are clean.
6.3.1.2 用纯化水清洗放料管、离心机。
Wash the discharge pipe and the centrifuge with purified water.
6.3.1.3 检查母液罐液面,保证本批母液不得溢出。
Verify the level of the mother liquid storage tank, and ensure the mother liquor is not out.
6.3.2 离心Centrifugation
6.3.2.1 开成品结晶罐罐底阀,开离心机放料阀,进少许料液,启动离心机至1速,运转正常后,转至2速,少量多次进料,至滤饼不超出离心机内栏2/3停止进料。
Open the bottom discharging valve of the crystallization tank, and the feed-in valve of the centrifuge, allow to discharge a little of