Does the ezfill 4500 comply with the USP media volume specification?
Yes. Chapter <711> specifies a volume accuracy of ±1%. The ezfill 4500 dispensing accuracy specification is “The Greater of 1% of Set Volume or ±5 mL”, guaranteeing that it is compliant for any volume ≥ 500 mL.
Doesn’t the USP specify a deaeration method that a media prep instrument must use?
No. The USP discusses deaeration with respect to dissolution media in two chapters: Chapter <711> and Chapter <1092>. Together they state:
- The listed “USP example method” of deaeration is merely “One method of deaeration”
- “Other validated deaeration techniques for removal of dissolved gases may be used.”
- “Other methods of deaeration are available and are in routine use throughout the industry”
- “Oxygen concentration below 6 mg/L has been found effective as a marker for adequate deaeration of water for the Performance Verification Test with USP Prednisone Tablets RS”.
There is no specified, required USP Method of deaeration to which media preparation instruments must adhere. The example method listed is only a suggestion, and as long as dissolved gases are sufficiently removed the instrument meets the USP recommendation.
Is the deaeration method used in the ezfill 4500 a “validated deaeration technique”?
Yes. The ezfill 4500 utilizes a slightly modified version of the “USP method” – filtering, heating the medium, and drawing a vacuum. Most importantly, it will reduce the dissolved oxygen to below the 6 mg/L level* determined to be adequate for the PVT test. “Comparison of the Effectiveness of Various Deaeration Techniques” by Degenhardt, et al ( Dissolution Technologies February 2004) shows this method to be just as effective as the “USP method”:
While the “USP method” yields slightly lower dissolved oxygen levels than the ezfill 4500 method immediately after degassing, the difference virtually disappears by the time the media has been transferred to the vessel and equilibrated, and certainly by the end of a 45 minute dissolution run. (*Note that the ezfill 4500 reduces the level of dissolved gases in the media by up to 3.0 ppm, to a level not less than 5.0 ppm.)
There is no measurement of vacuum levels verified during the Operational Qualification of the ezfill 4500. Why is this test not required?
The USP guidance does not require a specific vacuum value. (The only USP reference to a vacuum level is not in a guidance, only in the USP Dissolution Toolkit.) The only requirement for degassing is to reduce the dissolved oxygen to less than 6 mg/L to perform the PVT test, which is verified during the OQ.
The USP deaeration example method calls for filtering using 0.45μm filter, whereas the ezfill 4500 uses a 20μm filter. Why was this coarser filter chosen?
The USP method was specifically developed and optimized for performing the PVT. The PVT uses pure water, and therefore large volumes of media can be easily filtered using a 0.45μm filter. On the other hand, the ezfill 4500 is designed to work with a whole range of media, including more viscous and complex media such as FaSSIF/FeSSIF biorelevant media or those including surfactants. Filtering the entire range of media used in dissolution testing using a 0.45μm filter is impossible. Hence the reason for the use of a coarser filter in the ezfill. As an important side benefit, the frit-style filter employed in the ezfill 4500 can be easily flushed clean, making reuse possible with minimal cleaning and no carryover.
USP Chapter <711> specifies that the media used in dissolution testing must be 37°C ± 0.5°C, unless otherwise specified in the method. Doesn’t this mean this needs to be the specification of the heating of the ezfill 4500?
No. The reason is that what Chapter <711> specifies is the media temperature in the vessel in the beginning and for the duration of the dissolution test. Media temperature in the vessel depends on many things beyond the original temperature at which the media is delivered. Even if we dispense media precisely at 37°C ± 0.5°C, there is no guarantee that this will be the temperature at the start of the test. If the dissolution apparatus has not reached the appropriate temperature, or the vessel interior is at a cooler temperature due to heat loss to the ambient air, regardless of the dispensing temperature, the media can be at the wrong temperature at the time of the test. This is why the temperature of the media must still be manually or automatically verified just prior to the dosage form being introduced, exactly as with manual dispensing. This is further demonstrated by the example degassing method given in Chapter <711>, which only specifies the media temperature as precisely as “about 41°C”. (Note that the elevated temperature is recommended in anticipation of heat dissipation during the filling process, not to mention that the elevated temperature aids in the removal of dissolved gases in the media.)
Does Distek offer or recommend an algaecide for preventing water bath algae growth?
Although Distek does not sell this product directly we recommend using an algaecide designed specifically for use in water baths, incubators, circulators, and other similar temperature controlled lab equipment. Available products are Polyclean or Bath Brite which can be purchased through VWR.
What is the recommended method for cleaning dissolution baskets after a dissolution test is performed?
The baskets are made of 316 SS so they are resistant to many cleaning agents as long as the exposure is not for an extended duration. Most customers will use a MeOH rinse while the basket is still attached to the shaft allowing the waste stream to go into the dissolution vessel followed by a DI water rinse at the sink. Others will soak the baskets in a soap solution followed by a DI water rinse. So as you can see there is no one right answer but knowing the solubility and “stickiness” of your product will help determine the best cleaning approach. We suggest starting with a MeOH rinse followed by a DI water wash.
Is bathless dissolution heating USP compliant?
Yes. The use of bathless heating is fully compliant per USP General Chapter <711> which states, the vessel is partially immersed in a suitable water bath of any convenient size or heated by a suitable device such as a heating jacket. The water bath or heating device permits holding the temperature inside the vessel at 37° ±0.5°.
How do I level a Model 2500 Series dissolution system correctly?
- First make sure the surface where the dissolution system is placed is level and stable.
- Locate the 3 leveling feet of the instrument and loosen the nuts on the front feet using an open wrench. Loosen the two stabilizer feet located between the three leveling feet so that they don’t touch the surface of the table or bench.
- Place a minimum of 6 inch digital or carpenter’s level across the front of the base plate for the side to side measurement. Using the same level, measure the level on the left and right sides for the back to front level measurements. Adjust the leveling feet accordingly.
- Once the instrument meets the specification for level, tighten the locking nut on each foot with a wrench. Lower the stabilizer feet so that they barely touch the table or bench.
What information does Distek Support require when reporting a repair?
When reporting a repair, please provide the following information if available:
- Instrument make & model
- Instrument serial number
- Firmware version if known (Especially important for electronic problems)
- Contact person and location of instrument
- Describe any recent repairs or troubleshooting, if known
- Describe the exact problem (Include support images if available)