This is my long time we collected some information about filling lyophilized data, more information from the Internet, no expert knowledge, because knowledge is constantly updated and improved, knowledge is not experience, because knowledge also change rapidly development, so in a timely manner to learn and update knowledge, experience will be tested again. Knowledge does not shirk responsibility, experience often hides our eyes. The above information for your reference, and continue to learn and discuss together. And hope to be able to set off a wave of freeze-dried knowledge learning without images of their work, freeze-drying is not difficult, as long as willing to learn and think, believe that knowledge talents more timely and more reliable than experience, and we hope in the continuous learning and discussion to improve our lyophilized product quality.

Of course, collected here just a word or two each, the reason can be written in the article, not discussed here, the main point.

After lyophilization, the lower layer was reduced

Phenomenon: after lyophilization stratification, the lower layer atrophy. Or shrink the whole product. Part of the product is very good, some of the shrinking into almost empty bottles

Possible cause analysis and solution: no pre freezing, sublimation too fast

It is possible that the local temperature is too high or too much pressure leads to partial dissolution of the.

1, if you have a relatively small amount of drugs, it is prone to such problems.

2, shrink the product of the plastic plug seal is very good, on the contrary, if the product is relatively easy to absorb moisture will occur this phenomenon.

The main reason is that the following materials are not dry, out of the warehouse, the support of the material in the ice fusion and collapse

It is very likely that the material is too fast after entering the warehouse, the eutectic point of the material is not reached, the bottom of the material has a boiling phenomenon

Should be warming up a little faster, water did not take off, resulting in lower melting

May be the temperature of the vitrification of the drug is low, it is recommended to find reasons on the prescription

Why would the lower than the upper loose, you could see the clear channel because water sublimation is start at the top, when heated to above the eutectic point, the lower the moisture products because of heat absorption not timely sublimation result caused by autolysis.

This is normal, because we use the freezing technology it will take some time, the freezing time, some slightly soluble substances do not crystallize precipitation in the lower material, thus causing the material after freezing, the upper and lower layers is sublimation temperature of different causes, sublimation the. The method can reduce the sublimation temperature and prolong the sublimation time

Warming up a little faster, water did not take off, resulting in lower melting.

Warming caused by too fast! Different materials in the water after the full sublimation or negative, while the bottom of the water more than the local melting of the material layer!

Proper extension of drying time can effectively avoid this phenomenon!

Two, a layer of dry skin surface

Phenomenon: vacuum, the surface of a large number of vesicles, dry surface after a layer of separation. It's hard to see, sometimes floating boxes are all over the place.

I'm a biological agent. Recently, the sample was stratified. I used the 2ml vial. Filling volume is 1ml, the main products in the middle of the sample, from top to bottom.

What is the reason?

Possible cause analysis and solution: vacuum degree to meet the requirements before the surface of the material has been partially unfrozen pre freeze is not good, water is not finished

Fully frozen, pumping water bubbles formed when the overflow.

This phenomenon is mostly in the freeze-dried samples due to the surface migration. Can strengthen pre freezing solution.

Simple insulation to see the material

There are other reasons for the rapid sublimation.

This is my long time we collected some information about filling lyophilized data, more information from the Internet, no expert knowledge, because knowledge is constantly updated and improved, knowledge is not experience, because knowledge also change rapidly development, so in a timely manner to learn and update knowledge, experience will be tested again. Knowledge does not shirk responsibility, experience often hides our eyes. The above information for your reference, and continue to learn and discuss together. And hope to be able to set off a wave of freeze-dried knowledge learning without images of their work, freeze-drying is not difficult, as long as willing to learn and think, believe that knowledge talents more timely and more reliable than experience, and we hope in the continuous learning and discussion to improve our lyophilized product quality.

Of course, collected here just a word or two each, the reason can be written in the article, not discussed here, the main point.

After lyophilization, the lower layer was reduced

Phenomenon: after lyophilization stratification, the lower layer atrophy. Or shrink the whole product. Part of the product is very good, some of the shrinking into almost empty bottles

Possible cause analysis and solution: no pre freezing, sublimation too fast

It is possible that the local temperature is too high or too much pressure leads to partial dissolution of the.

1, if you have a relatively small amount of drugs, it is prone to such problems.

2, shrink the product of the plastic plug seal is very good, on the contrary, if the product is relatively easy to absorb moisture will occur this phenomenon.

The main reason is that the following materials are not dry, out of the warehouse, the support of the material in the ice fusion and collapse

It is very likely that the material is too fast after entering the warehouse, the eutectic point of the material is not reached, the bottom of the material has a boiling phenomenon

Should be warming up a little faster, water did not take off, resulting in lower melting

May be the temperature of the vitrification of the drug is low, it is recommended to find reasons on the prescription

Why would the lower than the upper loose, you could see the clear channel because water sublimation is start at the top, when heated to above the eutectic point, the lower the moisture products because of heat absorption not timely sublimation result caused by autolysis.

This is normal, because we use the freezing technology it will take some time, the freezing time, some slightly soluble substances do not crystallize precipitation in the lower material, thus causing the material after freezing, the upper and lower layers is sublimation temperature of different causes, sublimation the. The method can reduce the sublimation temperature and prolong the sublimation time

Warming up a little faster, water did not take off, resulting in lower melting.

Warming caused by too fast! Different materials in the water after the full sublimation or negative, while the bottom of the water more than the local melting of the material layer!

Proper extension of drying time can effectively avoid this phenomenon!

Two, a layer of dry skin surface

Phenomenon: vacuum, the surface of a large number of vesicles, dry surface after a layer of separation. It's hard to see, sometimes floating boxes are all over the place.

I'm a biological agent. Recently, the sample was stratified. I used the 2ml vial. Filling volume is 1ml, the main products in the middle of the sample, from top to bottom.

What is the reason?

Possible cause analysis and solution: vacuum degree to meet the requirements before the surface of the material has been partially unfrozen pre freeze is not good, water is not finished

Fully frozen, pumping water bubbles formed when the overflow.

This phenomenon is mostly in the freeze-dried samples due to the surface migration. Can strengthen pre freezing solution.

Simple insulation to see the material

There are other reasons for the rapid sublimation.

This is my long time we collected some information about filling lyophilized data, more information from the Internet, no expert knowledge, because knowledge is constantly updated and improved, knowledge is not experience, because knowledge also change rapidly development, so in a timely manner to learn and update knowledge, experience will be tested again. Knowledge does not shirk responsibility, experience often hides our eyes. The above information for your reference, and continue to learn and discuss together. And hope to be able to set off a wave of freeze-dried knowledge learning without images of their work, freeze-drying is not difficult, as long as willing to learn and think, believe that knowledge talents more timely and more reliable than experience, and we hope in the continuous learning and discussion to improve our lyophilized product quality.

Of course, collected here just a word or two each, the reason can be written in the article, not discussed here, the main point.

After lyophilization, the lower layer was reduced

Phenomenon: after lyophilization stratification, the lower layer atrophy. Or shrink the whole product. Part of the product is very good, some of the shrinking into almost empty bottles

Possible cause analysis and solution: no pre freezing, sublimation too fast

It is possible that the local temperature is too high or too much pressure leads to partial dissolution of the.

1, if you have a relatively small amount of drugs, it is prone to such problems.

2, shrink the product of the plastic plug seal is very good, on the contrary, if the product is relatively easy to absorb moisture will occur this phenomenon.

The main reason is that the following materials are not dry, out of the warehouse, the support of the material in the ice fusion and collapse

It is very likely that the material is too fast after entering the warehouse, the eutectic point of the material is not reached, the bottom of the material has a boiling phenomenon

Should be warming up a little faster, water did not take off, resulting in lower melting

May be the temperature of the vitrification of the drug is low, it is recommended to find reasons on the prescription

Why would the lower than the upper loose, you could see the clear channel because water sublimation is start at the top, when heated to above the eutectic point, the lower the moisture products because of heat absorption not timely sublimation result caused by autolysis.

This is normal, because we use the freezing technology it will take some time, the freezing time, some slightly soluble substances do not crystallize precipitation in the lower material, thus causing the material after freezing, the upper and lower layers is sublimation temperature of different causes, sublimation the. The method can reduce the sublimation temperature and prolong the sublimation time

Warming up a little faster, water did not take off, resulting in lower melting.

Warming caused by too fast! Different materials in the water after the full sublimation or negative, while the bottom of the water more than the local melting of the material layer!

Proper extension of drying time can effectively avoid this phenomenon!

Two, a layer of dry skin surface

Phenomenon: vacuum, the surface of a large number of vesicles, dry surface after a layer of separation. It's hard to see, sometimes floating boxes are all over the place.

I'm a biological agent. Recently, the sample was stratified. I used the 2ml vial. Filling volume is 1ml, the main products in the middle of the sample, from top to bottom.

What is the reason?

Possible cause analysis and solution: vacuum degree to meet the requirements before the surface of the material has been partially unfrozen pre freeze is not good, water is not finished

Fully frozen, pumping water bubbles formed when the overflow.

This phenomenon is mostly in the freeze-dried samples due to the surface migration. Can strengthen pre freezing solution.

Simple insulation to see the material

There are other reasons for the rapid sublimation.

This is my long time we collected some information about filling lyophilized data, more information from the Internet, no expert knowledge, because knowledge is constantly updated and improved, knowledge is not experience, because knowledge also change rapidly development, so in a timely manner to learn and update knowledge, experience will be tested again. Knowledge does not shirk responsibility, experience often hides our eyes. The above information for your reference, and continue to learn and discuss together. And hope to be able to set off a wave of freeze-dried knowledge learning without images of their work, freeze-drying is not difficult, as long as willing to learn and think, believe that knowledge talents more timely and more reliable than experience, and we hope in the continuous learning and discussion to improve our lyophilized product quality.

Of course, collected here just a word or two each, the reason can be written in the article, not discussed here, the main point.

After lyophilization, the lower layer was reduced

Phenomenon: after lyophilization stratification, the lower layer atrophy. Or shrink the whole product. Part of the product is very good, some of the shrinking into almost empty bottles

Possible cause analysis and solution: no pre freezing, sublimation too fast

It is possible that the local temperature is too high or too much pressure leads to partial dissolution of the.

1, if you have a relatively small amount of drugs, it is prone to such problems.

2, shrink the product of the plastic plug seal is very good, on the contrary, if the product is relatively easy to absorb moisture will occur this phenomenon.

The main reason is that the following materials are not dry, out of the warehouse, the support of the material in the ice fusion and collapse

It is very likely that the material is too fast after entering the warehouse, the eutectic point of the material is not reached, the bottom of the material has a boiling phenomenon

Should be warming up a little faster, water did not take off, resulting in lower melting

May be the temperature of the vitrification of the drug is low, it is recommended to find reasons on the prescription

Why would the lower than the upper loose, you could see the clear channel because water sublimation is start at the top, when heated to above the eutectic point, the lower the moisture products because of heat absorption not timely sublimation result caused by autolysis.

This is normal, because we use the freezing technology it will take some time, the freezing time, some slightly soluble substances do not crystallize precipitation in the lower material, thus causing the material after freezing, the upper and lower layers is sublimation temperature of different causes, sublimation the. The method can reduce the sublimation temperature and prolong the sublimation time

Warming up a little faster, water did not take off, resulting in lower melting.

Warming caused by too fast! Different materials in the water after the full sublimation or negative, while the bottom of the water more than the local melting of the material layer!

Proper extension of drying time can effectively avoid this phenomenon!

Two, a layer of dry skin surface

Phenomenon: vacuum, the surface of a large number of vesicles, dry surface after a layer of separation. It's hard to see, sometimes floating boxes are all over the place.

I'm a biological agent. Recently, the sample was stratified. I used the 2ml vial. Filling volume is 1ml, the main products in the middle of the sample, from top to bottom.

What is the reason?

Possible cause analysis and solution: vacuum degree to meet the requirements before the surface of the material has been partially unfrozen pre freeze is not good, water is not finished

Fully frozen, pumping water bubbles formed when the overflow.

This phenomenon is mostly in the freeze-dried samples due to the surface migration. Can strengthen pre freezing solution.

Simple insulation to see the material

There are other reasons for the rapid sublimation.

Nine analysis of the quality of freeze-dried products

Different products have different indicators of the quality of the products, such as moisture content, storage stability. The reduction of the survival rate, titer of live bacteria or drugs. The nutrient composition of food. The preservation rate of aromatic components. Many of these indicators need to use special equipment and inspection according to the relevant provisions of the standard in the freeze-drying method. The scene is mainly based on the shape analysis and judgment. Now according to my work experience and reference to many scholars of literature, the product shape to discuss and summarize the causes of it. A lot of hope all my colleagues to participate in the discussion, in order to improve together.

The lyophilized product of normal appearance is uniform color. The pore density, keep lyophilization volume. Basically the same shape, form a spongy mass structure. If there are any shells. Atrophy. Collapse. Empty. Ash scattered and broken phenomenon, is not a normal appearance, are substandard products, analyzed under the surface several.

1 products out of the box before the look is very good in quality, but out of the box shortly after shrinking, or hollow pieces. The reason is not completely dry products, there are residual ice. Out of the box, the temperature of the product. At the same pressure above the melting point, the ice melts into water, the water is around the already dry matter the absorption, resulting in cavitation. Shrinking phenomenon.

The product is not completely dry, may be caused by some of the following reasons

A. drying time is too short or the temperature is too low, or the combination of the two. If the thermometer, the vacuum gauge is normal, continuous batch drying is not complete, it should extend the drying time, improve the sublimation temperature when possible. If the quality of the products before normal. In May due to the loading error, the error rate of freezing, vacuum degree error cause, should also be appropriate to extend the drying time, may also be the thermometer is inaccurate. The actual temperature below the set temperature. Sublimation sublimation

B. freezing rate too fast. The grain is too thin, the sublimation rate slowed down. Because of reduced or empty cooling time is too long, the temperature is too low will cause the freezing rate to accelerate grain refinement, hinder the escape of water vapor, and therefore need to extend the drying time, or reduce the freezing rate.

C. is not completely frozen, freeze the gap or the formation of air resistance product and container wall, reduce the heat transfer effect. Due to the freezing is not complete, resulting in the vacuum sublimation freezing evaporation, the product of the volume, the gap formed in the product and container wall, heat cannot pass products. With the sublimation of freezing block around the first ice sublimation drying layer to form a layer of insulation surrounded by frozen lumps, the heat is more difficult to freeze, so the required drying time.

D. part of the product may be thoroughly dry. Between the shelf temperature is too high, the tray or shelf flexoelectrically too much, the bottle bottom Sheng products rough or uneven, or product packaging is caused by the uneven. For the inferior quality of the lyophilizer, only prolong the drying time, to make the most of the products water meets the requirements.

When the product is the skeleton structure of a large gap of the 2 products out of the box, even fluff, out of the box after the fluff and quickly dissipated. The main reason is the product formula contained in the solid material is too small, frozen, free water into pure ice volume increases, the pore is formed after sublimation that may make the useful components of flying together in the sublimation with water vapor. Fluff was formed in the solid products, once the air will absorb water vapor melt away. The solution is to increase the filler in the formula.

3 products out of the box, there are foam pit. Dry shrinkage. Collapse. Cavity defects. The main reason is that the freezing temperature is too high, or the time is too short, the product has not yet fully frozen; or the first stage when the drying temperature is too high, the pressure is too high, so that part of the product. In the melting caused by freeze sublimation time, quickly reduce the external pressure caused by bubbling; melting products have evaporated and concentrated, will be a shrinking shape; a part of the wet heating products due to excessive and melting, also can make the dry solid material dissolved in the part which has been caused by partial melting into the hollow stem or collapse. So the operation, must make the products frozen in prison, eutectic temperature cannot exceed the sublimation of products, it can not exceed the sublimation temperature jump solution temperature.

4 the color and porosity of the product are not uniform in the depth direction

May be due to the long time after the packaging, the solution can not be dissolved in the composition of precipitation

Ten, the impact of environmental temperature and humidity on the freeze-drying process

The effect of temperature and humidity on the environment is also in the front and out of the box before freezing

However, the temperature and humidity of the environment on the freeze-drying process, the time required for freeze-drying, and even the final products are frozen. The most prominent is the effect of relative humidity on the freeze-drying time!

The ambient temperature of the lyophilized product was not directly affected, have certain effects on the freeze drying machine of other equipment, such as refrigeration machine, if the ambient temperature is too high (not as central air conditioning condensation) will have a certain impact. Today's machines are generally not affected. If it's old-fashioned, it will have a big impact.

Eleven, determine the freeze-dried products and unqualified: stratification, atrophy, spray bottles, sticky bottom, discoloration, cavitation, moisture, clarity, insoluble particles, poor solubility, bubbling, dry shrinkage, dry, bottle appearance, etc.

Twelve, freeze-dried formula

There are rules for the freeze drying, Siping three climb up; pre frozen end of the vacuum, the vacuum began to dry; long stay before the eutectic point,

33 get the nine party. Freeze-dried formula notes:

There are rules that the law can be found; a: refers to a temperature; Siping four: refers to the process of heat preservation; the three climb: refers to the three heating; stay long: long holding time; 33: three three, the eutectic point before holding the remaining three times longer than the holding time 2~3 hours or 3~4 hours; we understand this * * *: refers to the beginning, to