The intrinsic dissolution rate is defined as the dissolution rate of pure substances under the condition of constant surface area, agitation-stirring speed, pH and ionic-strength of the dissolution medium.
The knowledge of intrinsic dissolution rate is vital in screening new drug candidates as it can help optimize the physiological effectiveness of new dosage forms. Distek has improved the performance and reliability of the rotating cylinder or “wood apparatus” with the paddle over stationary disk intrinsic apparatus. This is available in two configurations; standard for use with 1L vessel and mini for use with 100/200 ml vessels. The Distek design avoids the formation of air bubbles on the surface of the product and eliminates the potential of product “slippage” as can be the case with the wood apparatus.
The Distek standard and mini intrinsic apparatus consists of steel punch, die, and base plate (fig. A).
Test material is placed in the 0.8 cm diameter die cavity (optional cavity sizes are available) and the punch is inserted. The punch, die and press plate are placed in a laboratory press and kept under 2000 psi for 4-5 minutes. The press plate is disconnected from the die to expose a compact pellet of .5 cm2 surface area.
A Viton gasket is placed around the threaded shoulder of the die and a polypropylene plastic cap is screwed onto the threads. The assembly is then immersed, pellet side up, in the bottom of a flat dissolution vessel containing 900ml of dissolution medium at 37C. The paddle blade is positioned 6mm above the surface of the pellet and rotated at 50 rpm.
See USP 30-NF 25 General Chapter <1087> page 531 for more details.
Raise the dissolution drive head or individual shaft out of the vessel and attach the Distek Center-Chek™ to the stirring shaft per the below requirement.
When the shaft is properly inserted in the vessel the attached Center-Chek™ should be positioned no more than 2cm below the vessel flange.
FDA/ASTM Mechanical Calibration:
When the shaft is properly inserted in the vessel the attached Center-Cheks™ should be positioned so that the bottom centering tool is positioned 2mm above the top of the paddle blade or basket. The 2nd centering tool should be positioned 80mm above the paddle blade or 60mm above the top of the basket.
To install the Center-Chek™ onto the stirring shaft squeeze the legs gently together and attach to the shaft. Push inwards on the plastic tip of the Center-Chek™ while lowering the shaft into the vessel.
Caution: If the tip of Center-Chek™ is not pushed in as it is lowered into the vessel, it may snap off damaging the tool.
When the shaft axis and vessel axis are aligned correctly, as in Fig. A, the Center-Chek™ pointer should not exceed a total sweep of 4mm as it rotates 360° within the vessel.
Figure B corresponds to the maximum offset tolerance of 2mm from the center axis as described in USP 23. The Center-Chek™ pointer is allowed to sweep 2mm left and 2mm right during a 360° rotation, for a total deflection of 4mm.
The proper calculation for centering is the total measured sweep divided by 2.
Tip: If a vessel is slightly out of round, it may be possible to correct an offset condition by rotating the vessel in its mounting hole. An index mark should be made on the underside of the vessel flange and vessel plate. This allows easy restoration of correct alignment after the vessel is removed and replaced. The vessel should also be marked for identification, and be returned to the same vessel position on the same dissolution system. The Distek Premiere vessel includes an index mark and serial number for this purpose.
Fig. A: Shaft Centered in Vessel
Fig. B: Shaft Offset by 2mm
The embedded temperature sensor inside each of the hollow stirring shafts allow the EVOLUTION Series to continuously control, monitor, and record the temperatures of each individual vessel throughout the entire Dissolution test. Located inside and at the bottom most position of the shaft (red arrow below), the temperature sensors are able to continuously monitor the temperature of the media. Without the use of an external thermometer it eliminates any associated hydrodynamic effects. The EVO 6100 and EVO 6300 are the only dissolution systems on the market with this capability.
The shafts of the EVO 6100 and EVO 6300 are designed for 100% assurance that the medium temperature is maintained throughout the entire test. Also, it eliminates the need to remove the shaft when changing between apparatus 1 (baskets) and apparatus 2 (paddles) thanks to the use of detachable stirring elements and the height adjustment block.
Cipher instrument control software is a Windows based application designed and developed by Distek to remotely access and control our dissolution equipment.*
Cipher can be installed locally or networked providing full access to any Distek dissolution bath and autosampler from any appropriately connected PC running the application. Cipher allows the user to create and run methods, monitor instrument status, generate reports, and control users and manager logins. Cipher also offers the flexibility to set the level of security appropriate for your laboratory. When enabling all the security features and combined with the appropriate internally developed policies, Cipher will meet 21 CFR part 11 compliance.
* Cipher currently controls the Model 2100C, EVO 6100, 6300, and 4300
Procedure for priming your TCS 0200C Thermocirculator. Failure to properly prime the TCS will result in damage to the heater and/or pump.
1. Fill bath midway between the top of the bath inlet fitting and the lower outlet fitting, (dotted line in figure 2).
2. Attach a 3ft (1m) long x 5/8″ (16mm) ID drain tubing to drain valve.
3. Raise drain tubing to the vertical position (figure 1). The drain valve should be tilted up.
4. Open the drain valve to allow pump inlet tubing to fill with water for 5-10 seconds.
5. Slowly lower drain tubing to allow the tubing to fill with water (figure 2). Fill the tubing with as much water as possible.
6. Close the drain valve.
7. Lift drain tubing vertically and open the drain valve allowing the water to flow through the pump. Water should be observed exiting the TCS through the bath water inlet tubing and port.
8. Repeat steps 4-7 as necessary.
9. Close the drain valve.
10. Remove and empty the priming tubing from the drain valve.
11. Turn on the TCS power.
12. If water does not immediately begin to circulate turn off the TCS power and repeat the priming procedure.
Distek’s 2100C water bath-based dissolution system (pictured below) is known for being durable and user-friendly. However, your clients may not be aware of the versatility and customization that the 2100C offers. When configured at the time of the order, the Distek 2100C has the ability to support up to eight 2L vessels or four 4L vessels. Also, with the quad stir (pictured below) or the single station small volume kit the 2100C can support 6 to 24 positions at 100ml or 200ml.
Please note that an existing system cannot be upgraded to 2L/4L capabilities
The Distek ezfill 4500 is a compact, transportable, easy-to-use and surfactant capable media preparation station. Now dissolution media containing up to 2% surfactants can be degassed. The ezfill is equipped with a surfactant mode, SLS, which greatly reduces foaming issues seen in other media preparation systems.
When degassing surfactant based dissolution media, many laboratories add surfactants after the media has been degassed. Stirring surfactant into the media after degassing reintroduces gas back into the media.
SLS mode can be activated in advanced setup mode:
1) Simultaneously push the SETUP and UP arrow keys (pictured below).*
2) Press and hold the SETUP key until one of the following messages flashes: SLS ON or SLS OFF.
3) If necessary, use the UP or DOWN arrow key to switch to SLS ON.
4) Hold the SETUP key for 3 seconds to exit advanced setup mode.
*Do not hold the SETUP and DOWN arrow keys simultaneously.