2013 RIGGTEK Dissolution Test Systems. RIGGTEK – Dissolution Test Systems 11/2013 Company Presentation 2 Content 2 Media Preparation – Regulatory Demands

2013 RIGGTEKDissolution Test Systems

RIGGTEK – Dissolution Test Systems 11/2013Company Presentation 2

Content

2

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


Media PreparationRegulatory Demands – why?

The correct and repeatable media preparation has significant influence on the reproducibilty of the dissolution test results

Following parameters are important:

1. precise and repeatable mixing of the media

2. precise dispensing of the media into the vessels

3. timesaving warming of the media

4. degassing of the media

5. documentation of the media preparation.


Media PreparationRegulatory 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.


Media PreparationRegulatory Demands – degassing

USP:

„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*.“

*Dissoution Technologies, May 1996

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 .


Media PreparationRegulatory 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


Media PreparationRegulatory 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).


Media PreparationUser Demands – easy handling, space saving

easy handling:

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.

1. xx2. yy3. ww4. ...


DissoPrep X8 / X15features (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



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.).



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.



Degassing Efficiency Investigation with DissoPrep X8© 2010www.riggtek.comDipl.- Ing. Hansjuergen Riggenmann

Oxymeter from WTW OXI 330DissoPrep X8 with Firmware 7.108

Method Parameter Test No. 1 2 3 4 5 6 (7)Temperature °C 36 45,2 22,1 36,7 45,5 36,9 37,1Temperature eff. °C/10 360 452 221 367 455 369 371min. Pressure (vacuum) mbar 450 450 90 90 90 90 90Volume mL 1x 5000 1x 5000 1x 5000 1x 5000 1x 5000 6x 1000 6x 1000add. Degas Time sec 120 120 120 120 240 120 120

start Oxygen ppm O2 8,54 8,47 8,36 8,24 8,55 8,1 8,55

end Oxygen ppm O2 6,26 5,64 5,62 3,59 3,09 3,66 3,18DPX8 routine application(time saving method without add. Degas Time)

YES YES YES

0

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3

4

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6

7

0

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1 2 3 4 5 6 (7)

end

Oxy

gen

(pp

m)

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ssu

re (m

bar

) /

Tem

p. (

°C)

Test no.

Temperature

Pressure

end Oxygen

degassing:



1313

Not degassed Degassed degassing:



dispensing:

The vessels in the dissolution tester are filled directly with a Dispense Tube.

The highly precise dosage (<1% at 500 - 8.000g / 15.000g, 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 / 15.000g (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.


DissoPrep X8 /X15features (7)

DISPENSE PROTOCOLNo: 14for the media dosagewith DosaPrep X8Serial Number : 22020999Firmware Version: 6.000General Data:Nominal filter capacity [l]: 5000Remaining filter capacity [l]: 4827Volume throughput up to now : 173Method: 0Standard Media 0,1N HCLResult of the dosages [g]: MEDIUM ADDTV RATIO DEV%Fill Nominal: 5400 0.0 0.000Fill Actual : 5504 0.0 0.000 +0.0 MEDIUM DEV% ADDTV DEV%Vessel No. 6: 899 -0.1 0.0 +0.0Vessel No. 5: 901 +0.1 0.0 +0.0Vessel No. 4: 900 +0.1 0.0 +0.0Vessel No. 3: 900 -0.0 0.0 +0.0Vessel No. 2: 900 +0.0 0.0 +0.0Vessel No. 1: 900 -0.0 0.0 +0.0Temperature (average): 37.1 CMAX.VACUUM at 144 mbar absolute pressure *Date, Time: ............................Name: ............................Signature: ............................

documentation:



MANUAL CALIBRATION PROTOCOLNo: 7for the media dosagewith DOSAPREP X8Serial Number : 20100056Firmware Version: 4.25General Data:Nominal filter capacity [l]: 5000Remaining filter capacity [l]: 4950Volume throughput up to now : 50Result of the quantity measurings [g] INTERN EXTERN DEV% No. 8: 1003 1005 -0.2 No. 7: 1004 1004 +0.0 No. 6: 1004 1005 -0.1 No. 5: 1004 1003 +0.1 No. 4: 1003 1003 +0.0 No. 3: 1004 1003 +0.1 No. 2: 1004 1005 -0.1 No. 1: 1003 1002 +0.1Result (average): 1004 1004 -0.0Result of the temperature measurings[C] INTERN EXTERN DEV No. 8: 36.2 36.2 +0.0 No. 7: 36.3 36.3 +0.0 No. 6: 36.2 36.2 +0.0 No. 5: 36.2 36.2 +0.0 No. 4: 36.3 36.3 +0.0 No. 3: 36.3 36.3 +0.0 No. 2: 36.3 36.3 +0.0 No. 1: 36.3 36.3 +0.0Result (average): 36.2 36.2 +0.0Date, Time: ............................Name: ............................Signature: ............................ 2000-10-03 21:21:21 (UTC)

documentation:



documentation:


DissoPrep X8 / X15advantages (1)

easy handling:

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”.


DissoPrep X8 / X15advantages (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


Media PreparationRegulatory Demands – why?

The correct and always repeatable media preparation has significant influence on the reproducibilty of the dissolution test results

Following parameters are important:

1. precise and repeatable mixing of the media

2. precise dispensing of the media into the vessels

3. timesaving warming of the media

4. degassing of the media

5. documentation of the media preparation

with DissoPrep:

to remember...

1. xx2. yy3. ww4. ...


DissoPrep X8 / X15options / 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



Water-Interface

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



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


Autosampler „Sampilio X8“The result of your requests

easy to operate

first-in, first-out

reproducable

prepared for future tasks

reliable

expansible

easy to upgrade

easy to service

fast


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


Sampilio X8features (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).


Sampilio X8features 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.


Sampilio X8features 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.



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



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).



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.).



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.



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



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.



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.



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


Sampilio X8options / accessories (1)

DUAL

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



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



Sample Probes

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


easyDISS TX6 / TX8features 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.


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

easyDISS TX6 / TX8features and advantages (2)


Laser numbering and certification

for shafts, paddles, baskets, vessles, etc.

Teflon coated baskets and paddles

for aggressive media

rotating cylinders

for transdermal patches

easyDISS TX6 / TX8options and accessories (1)

diffrent vessels and vessel covers

vessels with clear glass or amber

EMC Ultra Precision Vessels low evaporation covers


Intrinsic Kit

easy to remove and clean with: built in drain drop round edges no leaks


Automatic Tablet Drop for simultanous drop of

dosage forms at all vessels

paddle over disk vessels with clear glass or

amber low evaporation covers


Immersion Cell

for testing semisolids


Small Volume Conversion Kit

for special dosage forms with lower concentrations

sampling accessories

for all kinds of automatic or manual sampling


calibration equipment

for calibration issues

accessories

we support you finding the correct dissolution accessories


https://www.dissolutionaccessories.com/dissolutionaccessories/product-database/psfil001-ca-a-1-micron-poroplast-filters-pack-100-/2303


Demo, Questions and Discussionplease feel free to ask all questions

Thank you for your attention

Any questions?

Documents

2013 RIGGTEK Dissolution Test Systems. RIGGTEK – Dissolution Test Systems 11/2013 Company Presentation 2 Content 2 Media Preparation – Regulatory Demands