Temperature of bath

[Dr RHISHIKANT]

USP mentions that the vessel is partially immersed in a suitable water bath of any convenient size that permits holding the temperature inside the vessel at 37°± 0.5° during the test (temperature of vessel) but does not say anything about the temperature of bath.

Is it necessary to display the temperature of bath on the dissolution apparatus with regulatory as well as cGMP point of view?

[kgauger]

The temperature of the bath only needs to be sufficient to hold the temperature of the vessels to 37 +/- 0.5°C. The actual temperature of the water is not important as long as the vessel temperatures are within specifications.

My lab records the temperature of each vessel both before starting the test and then again at the end of the test to show that the temperature was set and maintained correctly. We usually set the water bath temp at around 37.4 °C to achieve a 37.0°C temp in the 6 vessels.

[Dr RHISHIKANT]

Kgauger,

You are setting the temperature 37.4 in order to achieve 37 in the vessel. Whether this setting and the actual display of bath temperature is essential on the instrument or instrument should
display only vessel temperature?

[kgauger]

DR. RHISHIKANT,

Ideally an instrument would display the temperature of each vessel rather than the temperature of the water bath. The problem with doing that is that you need to have probes in the actual vessels to display the readings and those probes could impact your dissolution test. Having the bath temp displayed on an instrument does at least alert the users that the recirculator had failed in the middle of a long run, but that is about the only value added.

[CHRIS]

Normally dissolution testers have an external probe that people inmerse in the waterbath. A good idea, if you have a dissolution tester with more than 6 vessels is to fill one vessel with the same amount of media and monitor the temperature of this "control vessel": you measure initially the temperature of all vessels and assume that if the control vessel is 37°± 0.5° during all the experiment, the rest of the vessels should be within.

This may not be absolutely true, but it seems to be quite elegant for showing vessels temperature compliance.

By the way, if you do so, remove the paddle from this vessel, otherwise you will destroy the temperature probe!!.

[ppscott]

Originally the temperature specified in the USP was for the bath and the medium. But over time the usp realized that every system is different, every vessel different, and every bath different. Later versions of the USP read 37.0C+-0.5C in the vessel and do not specify the water bath.

The real issue is what goes on in the vessel. I could have my baths at 41, but if this is what is required to keep my vessels at 37 (I work at the north pole), then it impacts nothing in the vessel.

I actually use a bathless system. Heat well above 37C is applied directly to key points along the vessels surface. There is no difference internally that I have seen. I get equivalent results on a bath system

[vjf]

We have a temperature probe in the bath only. Prior to starting the test the probe is used to measure the temperatures in the vessels. The probe is then returned to the bath.

Over the last 10 years, I have observed that if the bath temperature is 37.3 to 37.4 our vessel temperatures are 37.1 - 37.2 c. We don't normally start our tests until the vessel temperatures at the beginning of the test are at least 37.1. If the bath temperature during the test remains constant at 37.3 or 37.4 the vessel temperature also remains 37.1 or 37.2.

[sarvesh]

It doesn't matter what is temperature of your dissolution bath (obviously above 37.0°C) if the temperature of the vessels is maintained at 37°C +/- 0.5°C.

The important thing is that the temperature of the dissolution bath should remains constant throughout the experiment, therefore temperature of the vessels.
That's iwhy it's always better to show the temperature of the bath for it's maintaining the temperature of the vessels.

[shantanu]

dear rishi,

if temperature of bath is around 90degree, u can get the temperature of vessel as 37degree, but maintaining the temperature constant at 37degree would be difficult since your process will last for 2or3 hrs.

so, i think they dont mention the temperature of bath.


regards,
shantanu

[Dr Smart]

Normally any dissolution Instrument has the bath temp displayed. For measuring the temperature of the vessel, external probes are provided which when inserted in each vessel gives the temperature of the vessels.

[story teller]

Word of warning on using the probe for the bath to measure the temperature of the vessels. Some temperature control units for disso baths use the reading from the probe to control the heating unit. If you have a unit configured this way pulling the probe out of the bath causes a low temperature reading. This causes the controller to kick on and in turn can cause the temperature in the vessel to go above 37.5.

[syx]

When we calib the thermoprobe for the bath, we put the calibrator (standardized thermometer) in the vessel, not in the bath. When temp of vessels reach 37 degree, we input the result as 37 though it has higher temp in the bath.

Temp check should be performed before disso test to be run to ensure the temp is in permitted range.

[Sharma]

USP mentions that the vessel is partially immersed in a suitable water bath of any convenient size that permits holding the temperature inside the vessel at 37°± 0.5° during the test (temperature of vessel) but does not say anything about the temperature of bath.

Is it necessary to display the temperature of bath on the dissolution apparatus with regulatory as well as cGMP point of view?

USP says to maintan the temperature of the vessles and this is important. USP says to record the temp of all the vessles before dropping the tablets and during the run.

It is not possible to maintain the vessles temperature 37±0.5°C without keeping the water bath temperature slightly higher. ********** has mentioend in their manual to keep the bath temp at 37.7 to get 37 inside the vessels.

[vishalmodi]

Dear Shantnu,

You have to assure constant vessel temperature 37.0°c by keeping bath temperature constant it may be 41°c or any. If bath remains at constant temperature automaticall the vessel temperature will be remain constant. So U have to find at which Bath temperature your vessel get 37°c.
dear rishi,

if temperature of bath is around 90degree, u can get the temperature of vessel as 37degree, but maintaining the temperature constant at 37degree would be difficult since your process will last for 2or3 hrs.

so, i think they dont mention the temperature of bath.


regards,
shantanu

[GBC]

The most interesting that strikes me as I have read through the posts on maintaining temperature at 37.0 +/- 0.5 degrees in the vessel contained in a water bath is the fact that no one has mentioned the level of water in the water bath. For instance, if the bath temperature is kept at 37.3 degrees and the level of circulator water is above the level of medium in the vessel, proper temperature will be controlled. If the bath temperature is kept at 37.3 degrees and the level of circulator water has fallen to about two thirds of the height of medium in the vessel, proper temperature will not be maintained in fact, it will probably be below 36.0 degrees.The bath temperature offset is only effective when training and procedures are in place to maintain the circulator water at a height above the level of medium in the vessel. Lastly, all of this is in jeopardy if the vessel is not properly covered to guard against drafts which will also affect vessel temperature.

[oldbear]

We have over 50 disso App 1 and 2 baths. Each bath is different!!! As part of the 6 month PQ we map the individual vessels with the bath temperatue. We have found that the temperature controllers and baths (6 vs 8) positions are different in the temperature required to hold temp in the vessels. We test them for 24 hours using min/max thermometers running with paddles at 120 rpm, 900 mL water. The specification is 37 +/- 0.5 but we find we can do better and have an action limit of 37+/- 0.2. The bath temperature adjustment will change as the heater/recirculator gets older and/or the temperature probe changes. By mapping the vessels you can find hot or cold kettels and find problems in your system. By this method we determined that in certain 8 kettle baths all positons required a kettle to keep within our action limits. If not there then the we observed the vessel nearest the inlet was 0.4 C high and the two exit vessels were 0.3 low. This is too much of a spread and we could see this difference in one of our products. We map AS FOUND and AS LEFT and we will adjust the bath temperature to keep within our action limit. Make sure your analysts keep the water bath at the correct height. We measure bath temp before and after each test and we measure before and after temp in each vessel. With a good PQ one has a lot of confidence in the reliability of our disso work.

[rc_12321]

I think it is quiet important at this juncture to look at the temperatue coefficint of the material with which our vessels made of.I think the manufacturer provides you information on this.Though USP is not interested on your bath temperature, one should not set it at the temp as one likes.We do not know what kind of changes our meterial under goes at elevated temperatures. With my practical knowledge, i can say it is little diffficult to mantain required temp if your volme is 500 ml, but with volumes like 900 ml i did not see any difficulties even for 12 and 24 hour long runs.

[ashwanijoy]

Thought process behind displaying the temperature of bath is that temperature of vessel is maintained constant to match in-vivo consition.Regulatory bodies could be convinced if you r recording in greem sheet or labnotebook (initial temperature and final temperature ),after dissolution is complete.Display of temperature is for benefit of analyst handling the dissolution.
regards