2. Content Media Preparation – Regulatory Demands
Media Preparation – User Demands
DissoPrep X8/15 – features, advantages, options
Sampilio X8 – features, advantages, options
easyDISS TX6 / TX8 – features, advantages, options 2

3. Media Preparation Regulatory Demands – why?
The correct and repeatable media preparation has significant influence on the reproducibilty of the dissolution test results
Following parameters are important:
precise and repeatable mixing of the media
precise dispensing of the media into the vessels
timesaving warming of the media
degassing of the media
documentation of the media preparation. 3 3 3

4. Media Preparation Regulatory Demands – mixing, heating, dispensing
USP:
„Place the stated volume of the dissolution medium with an ...
... accuracy of 1% in the vessels ...
... and equilibrate it to 37 +/- 0,5 °C...“
„Standard Conditions“ for filling the vessels:
reference temperature according USP is 25°C:
1 Litre of Water weighs 998,3g
Standard Conditions according EP is 20°C and 1bar:
1 Litre of Water weighs 997,1g
Conclusion:
The „Stated Volumes“ – when mixing of all components of the media - must be filled cold at „Standard Conditions“ into the vessels and then heated up.
In accordance with the USP e.g. 900ml dispensed into a vessel weigh 897,4g. Only the weight of a liquid is not changing when warming it! Density and volume are changing!
It would be wrong to measure warm media in a volumetric flask or device calibrated at 20°C.
It would be wrong to use the specific weight (density) for gravimetric volume measuring of the media at e.g. 37°C. 4 4 4

5. Media Preparation Regulatory Demands – degassing USP: FDA:
„The USP recognizes that dissolved gases in the dissolution media may affect dissolution test results and ...
... recommends that gases be removed by filtering, warming and stirring under vacuum before the test is performed*.“
FDA:
The FDA targeted the degassing more than ever as an area of concern. The recommended method* refers to parameters of the USP recommendation „filtering, warming, stirring, vacuum and process time“. Stirring is realized by feeding air bubbles in the media bin. Additionally feeding air bubbles causes an Avalanche-Effect .
*Dissoution Technologies, May 1996 5 5 5

6. Media Preparation Regulatory Demands – degassing Experiences:
there were not published many and clear experience reports on the consequences of various degassing methods till now *. Usually, internal company experiences are not pubished.
a high theoretical degassing efficiency of an arbitrary degasing method is reduced by fast resaturation of dissolved air in the media. The re-aeration takes place during intermediate storage, during filling, during waiting periods and in the initial phase of the dissolution test.
under dissolution test conditions with degased media at least the dissolved air in the media may not be oversaturated, i.e. no formation of bubbles may arise.
In case of water with a temperature of 20°C and an ambient air pressure of 1bar, there are 9,08ppm oxygen and air components dissolved. In case of 37°C there are 6,72ppm. If the temperature is increased to 100°C and / or the air pressure is reduced against 0 bar (full vacuum), no more air can be solved.
Conclusion:
The degassing is necessary at least to avoid oversaturation.
The media can be dagassed either with the parameter „temperature“ or „vacuum“.
The results of different degassing methods must be compared after dosage into the vessel or at the start of the dissolution test.
*Dissoution Technologies, May 1996 / Dissoution Technologies, Feb 2004 / Dissoution Technologies, Aug 2008 6 6 6

7. Media Preparation Regulatory Demands – documentation GLP / GMP:
The GLP / GMP rules demand a prescribed handling method SOP for the production of the media and ...
... the documentation of all working steps has to be done (traceability). 7 7 7

8. Media Preparation User Demands – easy handling, space saving
The handling must be simple and convenient. Efficiency is increased only in connection with the...
... full acceptance of the equipment by the laboratory staff.
space saving:
Nowhere in the labs is enough space available...
... such a unit must be compact.
time and cost saving:
Media filtering, heating, mixing, and degassing must be performed without user intervention in a reasonable time...
... for increasing throughput, avoiding manual media handling and waiting for warming the media before the start of the dissolution test. The compliance of the regulations and standards saves a lot of operational and administrative work.
USP, EP, FDA, GLP/GMP comformity:
There are many different requirements from regulations and standards, generating a lot of additional work...
... such a unit has to comply all requirements and has to save all associated operational and administrative work. xx yy ww
... 8 8 8

9. DissoPrep X8 / X15 features (1)
The Dissoprep X8 / X15 is the original media preparation system which is working according the gravimetrical principle for more than 14 years and so fulfills the USP, FDA, EP, GLP / GMP.
GRAVIMETRICAL PRINCIPLE (lockout spec)
NO FLUDIC PUMP (lockout spec)
mixing of acid or buffer
high dispensing accuracy
complete printout / documentation
high degassing efficiency
8 or 15 liter tank
fast economic amortisation 9 9 9

10. DissoPrep X8 / X15 features (2)
The Dissoprep X8 / X15 is filtering, mixing, warming, degassing and dispensing the media according the USP, FDA, EP, GLP / GMP.
filtering:
by an easily exchangeable Filter Cartridge, the remaining filter capacity is checked automatically, when necessary the system prompts the user to change the filter. The Flow Through Principle prevents bacterial growth.
warming:
A special continous-flow heater warms the media before degassing. This generates an enhanced degassing and saves considerable time when heating in the dissolution tester.
Mixing:
For the precise addition of concentrated hydrochloric acid, buffer or surfactant (SLS) a second inlet channel is provided.
The composition of additive and water is controlled gravimetricly by a Precision Load Cell.
An electronic stirrer mixes the components in the storage tank and ensures a homogenous mixture concentration (functionally monitored).
The precision of the composition is very high (deviation lower than 0,2% typ.). 10 10 10

11. DissoPrep X8 / X15 features (3) degassing:
The media is exposed to a high vacuum during sucking in the raw media.
The interaction of heating, mixing and degassing generates an effective de-aeration of the medium e.g. for water with typically 3-5ppm O2 (after filling into the vessel).
The USP does not specify degassing in figures because the dissolved oxygen measurement is not robust and no traceable standards for the calibration of oxygen meters are available.
Only the physical effect paramaters temperature, vacuum and duration of media exposure can be measured reliably. 11 11 11

12. DissoPrep X8 / X15
features (4)
degassing: 12 12 12

13. DissoPrep X8 / X15 Not degassed Degassed features (5) degassing: 13 13

14. DissoPrep X8 / X15 features (6) dispensing:
The vessels in the dissolution tester are filled directly with a Dispense Tube.
The highly precise dosage (<1% at g / g, typ. 2g) of 900mL needs approximately 25 seconds and is controlled by the Precision Load Cell.
The target volume can be selected between 150g and 8.000g / g (weight equivalents of mL).
documentation:
All internal dosage processes are accurately controlled and monitored by a Precision Load Cell.
The individual dosage processes are documented and can be printed on an external printer or administrated with PC (Option: RC Software).
After each DISPENSE cycle the DissoPrep provides a DISPENSE Protocol containing the weights, the mixing ratio, the vacuum and the temperature.
Also a CALIBRATION Protocol is provided. The DissoPrep can be calibrated trough a software guided procedure easily. 14 14 14

15. DissoPrep X8 /X15 features (7) documentation: 15 DISPENSE PROTOCOL
No: 14
for the media dosage
with DosaPrep X8
Serial Number :
Firmware Version:
General Data:
Nominal filter capacity [l]:
Remaining filter capacity [l]:
Volume throughput up to now :
Method: 0
Standard Media 0,1N HCL
Result of the dosages [g]:
MEDIUM ADDTV RATIO DEV%
Fill Nominal:
Fill Actual :
MEDIUM DEV% ADDTV DEV%
Vessel No. 6:
Vessel No. 5:
Vessel No. 4:
Vessel No. 3:
Vessel No. 2:
Vessel No. 1:
Temperature (average): 37.1 C
MAX.VACUUM at 144 mbar absolute pressure *
Date, Time:
Name:
Signature: 15 15 15

16. DissoPrep X8 / X15 features (8) documentation: 16 16 16
MANUAL CALIBRATION PROTOCOL
No: 7
for the media dosage
with DOSAPREP X8
Serial Number :
Firmware Version:
General Data:
Nominal filter capacity [l]:
Remaining filter capacity [l]:
Volume throughput up to now :
Result of the quantity measurings [g]
INTERN EXTERN DEV%
No. 8:
No. 7:
No. 6:
No. 5:
No. 4:
No. 3:
No. 2:
No. 1:
Result (average):
Result of the temperature measurings[C]
INTERN EXTERN DEV
No. 8:
No. 7:
No. 6:
No. 5:
No. 4:
No. 3:
No. 2:
No. 1:
Date, Time:
Name:
Signature:
:21:21 (UTC)
documentation: 16 16 16

17. DissoPrep X8 / X15
features (9)
documentation: 17 17 17

18. DissoPrep X8 / X15 advantages (1) easy handling: space saving:
The user-interface of the DissoPrep is quite simple with only a few buttons.
The Remote Control Nozzle simplify the dispensing into the vessels.
space saving:
The dimensions of the DissoPrep X8 / X15 are W 30cm x H 66cm x D 59cm quite compact to fit in every lab.
USP, EP, FDA, GLP/GMP comformity:
DissoPrep fulfills all requirements of the media preparation according to the demanded rules of the USP and EP, as well as according to the recommendations of the FDA and of the GLP/GMP.
Safety in the Laboratory:
By automating the process - particularly the acid preparation and media dispensing - the risk to laboratory personnel is minimized.
Reproducibility of the results:
Reproducibility of the test results is independently of the operators
(a result of the automation of the media preparation).
Simplification of administrative documentation:
With the optional available Remote Control Software all methods can be administrated and all protocols which are generated with the DissoPrep can be transmitted in a PC network “21CFR Part 11 compliant”. 18 18 18

19. DissoPrep X8 / X15 advantages (2)
time and cost saving:
The saving of time is considerable. E.g. the DissoPrep X8 prepares up to 8L of dissolution media automated in less than 15 minutes (12 minutes with prepared media). The fast and precise dosage by a tube into the individual vessels (~25 seconds for 900ml) saves time-consuming handling steps. The preheated media saves up to 45 minutes for media heating with a conventional water bath dissolution tester.
If you calculate with:
180€ full costs of a manual test and
30€ costs of a test with the DissoPrep X8,
the ROI will already be reached after 90 tests 19 19 19

20. Media Preparation Regulatory Demands – why?
to remember...
The correct and always repeatable media preparation has significant influence on the reproducibilty of the dissolution test results
Following parameters are important:
precise and repeatable mixing of the media
precise dispensing of the media into the vessels
timesaving warming of the media
degassing of the media
documentation of the media preparation
with DissoPrep: xx yy ww
... 20 20 20

21. DissoPrep X8 / X15 options / accessories (1) DissoPrep X8 or X15
X8 with 8 liter tank
X15 with 15l tank (gross)
same housing dimensions
same working principle
RC-Nozzle
comfortable remote-controled dispensing with buttons at handle bar at tubing´s end
especially if 3m distance (tubings length) is used
RC-Software
Remote-Control-Software for easy method configuration and
easy protocol and certification administration 21 21 21

22. DissoPrep X8 / X15 options / accessories (2) Water-Interface LabCart
for continous, pressureless contection to DI-water tap
installation has to be done from house technicans of customer
shut-off valve should be installed
LabCart
comfortable use of DissoPrep at different places
place for different reservoirs (available at RIGGTEK), printer and vessel-rack
has to be connected to power-supply during whole media preparation and dispensing
UPS (uninterruptable power supply) not available at the moment (in work)
Vessel-Rack
safe transportation of vessels to dissolution tester
isolation keeps vessels warm
available for 6 or 8 vessels 22 22 22

23. DissoPrep X8 / X15 options / accessories (3) printers
for immediate protocol / certification printout
suitable parallel-printers in DINA4- or bon-paper-size
measuring equipment
all necessary measuring equipment for qualification of the DissoPrep is available at RIGGTEK
special balance with automatic communication to DissoPrep for easy and comfortable qualification 23 23 23

24. prepared for future tasks
Autosampler „Sampilio X8“
The result of your requests
reproducable
fast
reliable
prepared for future tasks
expansible
easy to service
first-in, first-out
easy to upgrade
easy to operate 24 24 24

25. Autosampler „Sampilio X8“
We heard the problems with autosampling
Do your customers have the following problems with their existing Autosamplers?
The pumps are not reliable
The samples taken with your autosampler are not comparable with the manual sampling
The cross-contamination between samples is too big
The possible intervals are not short enough for your desired sampling times
The autosampler is not easily to connect to different types of dissolution baths
The overall handling with the autosampler is complex, the operating is complicated
The cleaning and maintenance of the autosampler is time-consuming
Your autosampler is not equipped for future tasks such as cooling / heating and direct offline / online transfer to UV / HPLC .
We have solved these problems with the Sampilio X8 25 25 25

26. Sampilio X8
features (1)
The Sampilio X8 is the new generation of dissolution autosamplers
reliable with SMALL VOLUME DIAPHRAGM PUMPS (lockout spec)
compareable to manual sampling – FIFO delivery principle
lowest cross contamination
extremly short interval times
easy conntection to other dissolution testers
easy handling and operation
easy cleaning and maintenance
flexible for the future (Connectivity (in development), Cooling-Option (in development), Transfer-Module-Option (to be customized). 26 26 26

27. Sampilio X8 features and advantages (2)
Reliable with small diaphragm pumps
The small volume bidirectional diaphragm pumps (unique feature) for each line allow a simple functional principle without the need of additional valves, fittings etc.
and so guarantee less components which could be getting defect
The diaphragm pumps do not produce wrapped-off parts such as syringe pumps do, so you will not find any particle of seals, etc. in your samples. 27 27 27

28. Sampilio X8 features and advantages(3)
Compareable results as manual sampling
The small volume diaphragm pumps (unique feature) for each line allow with their lowest dead volume FIFO delivery principle
together with the lowest tubing volume – because of the working principle – the sampling is compareable with the manual sampling with syringe
The diaphragm pumps do not produce wrapped-off parts such as syringe pumps do, so you will not find any particle of seals, etc. in your samples. 28 28 28

29. Sampilio X8 features and advantages (4) Lowest cross contamination
The functional principle of the Sampilio X8 with small tubing length and small dead volume of the diaphragm pumps allow
together with the test tubes in the first row of the racks lowest cross contamination. Additional a cleaning of an „waste bin“ is not necessary.
200cm
40cm 29 29 29

30. Sampilio X8 features and advantages (5) Extremly short interval times
The functional principle of the Sampilio X8 with small tubing length, small dead volume of the pumps and so total small total dead volume allow fast flushing, sampling and recycling.
This results in the possiblility of extremly short interval times between the sampling steps (typ. < 2min). 30 30 30

31. Sampilio X8 features and advantages (6)
Easy connection to dissolution baths
Easy connection: For each line there is a 3m long tubing coming out of the Sampilio X8. The UNF ¼” -28 screw head fittings used at the tubings end are a standard for easy connection to sample probes, syringe filters or luer adapters.
There are different sample probes and stoppers available to fit all kinds of dissolution baths (DISTEK, Erweka, Sotax, etc.). 31 31 31

32. Sampilio X8 features and advantages (7) Easy operation and handling
Easy operation: Turn on the Sampilio X8. With only 5 keys and a easy menu structure you operate the Sampilio quickly and intuitively.
Easy handling: With only 6 tubes (one for each vessel) there are no unnecessary tubings between pumps and collectors, etc. . Open the door of the Sampilio X8 and insert rack filled with HPLC-Vials or Test Tubes on the rack carriage and close the door again - the Sampilio is ready for your sampling method. 32 32 32

33. serial configruration
Sampilio X8
features and advantages (8)
Easy cleaning and maintenance
The housing of the Sampilio X8 is completely closed and therefore easy to clean
For the flush volume so called "Waste tubes" are used. These are commercially available "Test Tubes / sample tubes“, that are placed in the first row of the rack and after a sample method they can be easily replaced / thrown away. A cleaning of any tank is not necessary.
Since the tubings and diaphragm pumps are installed in series without any valves in between, they can be cleaned with an automatic cleaning program easily and efficiently.
The mechanism is kept simple and robust and does not require expensive maintenance.
row for „Waste Tubes“
serial configruration 33 33 33

34. Sampilio X8 features and advantages (9)
Flexible for the future - Connectivity (in development)
The Sampilio X8 has different interfaces to communicate with different units and softwares (Media Preparation Systems, dissolution baths, UV´s, HPLC´s, Data-Software)
A software will collect and summarize all datas for a complete dissolution test. 34 34 34

35. Sampilio X8 features and advantages (6)
Flexible for the future - Cooling option (in development)
A Peltier Element will allow together with the closed housing a cooling of the collected samples and so reduces additional effort to take each collected sample to a refrigerator
For drying the inside of the Sampilio X8, a heating will be possible as well. 35 35 35

36. Sampilio X8 features and advantages (7)
Flexible for the future – Transfer Module-Option (to be customized)
The Transfer Module-Option will allow in combination with one pump for each line a flexible configuration of the Sampilio X8
So the transfer of a single sample, a sample row as well as media replacement or transfer to UV (or HPLC) in online- or offline-configuration will be possible 36 36 36

37. Sampilio X8 options / accessories (1) DUAL Additional Lines Racks
as DUAL-configuration two Sampilio´s are connected via USB (max. 2m distance) to allow an autosampling at a simultanoues dual dissolution test with max. 16 positions
special price for the DUAL-configuration
The Slave-Unit does not work independently
Additional Lines
as standard, the Sampilio X8 has 6 sample lines
up to two additional lines can be added
Racks
as standard the Sampilio X8 is delivered with one Test-Tube-Rack and one HPLC-Rack
for a possible rack-change additional racks are available 37 37 37

38. Transfer-Module-Option
Sampilio X8
options / accessories (2)
Cooling-Option
(in work)
will allow cooling to safe taking collected samples to a refrigerator after each sampling step
heating will possilbe for drying the inside of the Sampilio X8
Transfer-Module-Option
(in work)
the Transfer-Modul will allow single offline transfer of samples to an UV
or will allow replacement of media
RC-Software
(in work)
as standard the Sampilio X8 is delivered with one Test-Tube-Rack and one HPLC-Rack
for a possible rack-change additional racks are available 38 38 38

39. Sampilio X8 options / accessories (3) Sample Probes Filters
diffrent sample probes are available for a correct connection to a dissolution tester (e.g. Sotax, Distek)
Filters
different filters – disc, canuales, syringe -are available
luer adapters
diffrent kinds of luer adapters are available for optimal connection of the tubings 39 39 39

40. easyDISS TX6 / TX8 features and advantages (1)
The easyDISS TX6 / TX8 is all you really need at a dissolution tester
Rugged, compact and easy-to-use
Conforms to all current Ph.Eur. And USP specifications
Available with 6 (TX6) and 8 positions (TX8)
Screw-in baskets/paddles allow method changes in seconds
Individual clutches allow each shaft to be raised, lowered and engeged independent of the drive head
Uncluttered design allows maximum access to working area
316 stainless steel teflon coated vessel support plate
„Easy-Centre“ vessel centring system
One piece PETG water bath with built- in drain tap: no leaks; easy to remove and clean
Independent digital heater/circulator with over-temperature cut-out and indicator.
Full printed test report on completion of the run
RS232 bi-directional interface and USB/parallel printer port
Menu guided calibration procedure (with print-out)
Various options and accessories available. 40 40 40

41. Interchangeable Baskets/Paddles
easyDISS TX6 / TX8
features and advantages (2)
Interchangeable Baskets/Paddles
for method changes in seconds
„Easy-Centre“
Vessel Location
ensures that the vessels are perfectly centred very time
vessel easy to remove and locate
one piece wather bath
easy to remove and clean with:
built in drain drop
round edges
no leaks 41 41 41

42. easyDISS TX6 / TX8 options and accessories (1)
Laser numbering and certification
for shafts, paddles, baskets, vessles, etc.
diffrent vessels and vessel covers
vessels with clear glass or amber
EMC Ultra Precision Vessels
low evaporation covers
rotating cylinders
for transdermal patches
Teflon coated baskets and paddles
for aggressive media 42 42 42

43. easyDISS TX6 / TX8 options and accessories (2) paddle over disk
vessels with clear glass or amber
low evaporation covers
Automatic Tablet Drop
for simultanous drop of dosage forms at all vessels
Intrinsic Kit
easy to remove and clean with:
built in drain drop
round edges
no leaks 43 43 43

44. Small Volume Conversion Kit
easyDISS TX6 / TX8
options and accessories (3)
sampling accessories
for all kinds of automatic or manual sampling
Small Volume Conversion Kit
for special dosage forms with lower concentrations
Immersion Cell
for testing semisolids 44 44 44

45. calibration equipment
easyDISS TX6 / TX8
options and accessories (4)
calibration equipment
for calibration issues
accessories
we support you finding the correct dissolution accessories 45 45 45

46. Thank you for your attention
Demo, Questions and Discussion
please feel free to ask all questions
Thank you for your attention
Any questions? 46 46 46