Tablet Dissolution

Tools for Tablet Dissolution

Using rotating baskets for tablet dissolution was the first official method and was established in 1970. This method is now known as Apparatus 1 or Method 1. The metallic drive shaft of the apparatus is connected to the cylindrical basket. The basket is positioned inside a vessel made of glass or other inert, transparent material. To keep the vessel contents at a constant temperature, they are placed inside a water bath or heating jacket. The rotating basket smoothly stirs the solution in the vessel. Dissolution baskets should be perfectly round, not deformed, with the correct and verified mesh size. The USP Method 1 requires a 40-mesh screen unless otherwise specified in the monograph. Other meshes can be used to solve individual problems.

Dissolution Baskets

Mesh Openings

The clogging of the mesh openings by particles or excipients or the random release of particles through the mesh to the bottom of the vessel are one of the biggest problems associated with the basket method. Suppository Baskets are from plastic, these baskets have vertical slots instead of mesh. This facilitates dissolution and prevents blocking and/or clogging of the mesh opening, particularly when oil-based suppositories are used. Sintered Mesh stainless steel baskets have welded joins at all the wire overlaps and adds considerable strength and longevity to the basket. Sintering is a strengthening process that compresses and heats the mesh under high pressures and temperatures. Baskets with a wide variety of mesh openings are available and if the disaggregated particle size is consistent, a variation of mesh size may solve some difficult dissolution problems.

Care and maintenance

The mesh of the dissolution baskets is easily bent and so they should only be handled by the rim. This also prevents oily deposits from fingers left on the mesh. Care should be exercised to ensure that baskets are clean prior to use and to ensure there is no contamination between tests. Correct storage of the baskets can extend their life. Baskets can easily be stored in the supplier’s case or using a specially designed basket holder.

Basket Shafts

As a part of Apparatus 1 the basket shaft is a metallic drive shaft which is attached to the cylindrical basket. They are available in two different versions, the spring-clip style and the O-ring style:

• Spring Clips: the standard version of the dissolution basket is created so that the basket shaft is attached to it through the spring clips. As time passes, these clips can bend or corrode which can lead to excessive wobble of the dissolution basket on the shaft.
• O-Ring: the clipless basket is attached to the shaft using an O-ring instead of the spring clips. While it can be argued that this design reduces wobble and is easier to use, the USP still specifies the use of clips and proof of equivalence may be required if a clipless alternative is to be used.

Care and Maintenance

Proper storage of the shafts is extremely important - a bent or corroded shaft fails to comply with USP regulations, so it is crucial not to store shafts on a table or loose in a drawer where damage or corrosion can occur. The right way to store is e.g. in a basket shaft or paddle holder as it can prevent occuring damage.

Filters for Tablet Dissolution

In dissolution testing filters are essential to prevent particles of tablets from getting into the sample and thus affecting the spectrophotometer of HPLC results. The filters are designed to not adsorb any compounds of interest and are guaranteed chromium and heavy metal free to avoid interference with your analysis. Various filter types such as Cannula Filters, Filter Discs and Filter Tips are available.

QLA high-quality filters for Dissolution

Manufactured from Pure Quality material, QLA filters are fabricated in special moulds in clean-room conditions to ensure the best manufacturing practices. Samples from each batch are then tested for dimensional accuracy and then further tested for heavy metal content, inorganic interference and other possible contaminants.

Genuine QLA filters are guaranteed suitable for dissolution testing and CERTIFIED to be compliant with USP standards. So you can be certain that every batch of every filter will be consistent and the same as every other batch.

Cannula Filters

Cannula Filters are used when high levels of particulate are present. They generally have a large surface area and may affect the hydrodynamics in the vessel. However they have a good flow rate and may be used to prevent particulates blocking the sample probes. A large porosity range is available. There are some points to take into consideration when it comes to choosing the right cannula:

• Sampling Position: the correct position of the sampling is particularly important for tests with baskets as there can be a concentration profile between the stirring element and the bottom of the test vessel. There are different positions depending on wheter a test with 500ml or 900ml is performed.
• Cannula Length: considering the test volume, there are various lengths of the cannulae. A cannula with 120mm is used for 900ml, 197mm is used for 500ml and other lengths are normally used for "through the head sampling" whereby the cannula passes through the drive head of the dissolution bath.
• Cannula Material: the cannulae are usually made of stainless steel or PEEK - that way they don't adsorb or interfere with the active ingredient.
• Stoppers: the cannulae can be used with stoppers during the manual sampling to guarantee that the sample is taken from the same depth each time. Stoppers are connected to the cannulae and remain in a hole in the vessel cover. If these are to be used then it is crucial to ensure that the stopper and cannula match the vessel cover type.

Filter Discs

Filter Discs have a lower surface area than a cannula filter. In-Line Filter Discs (or filter frit) are recommended for use of low volume sample probes. These filter discs are designed to keep the filtration process outside the vessel but may suffer from blocking due to the lower surface area. To avoid blocking, go for the Hi-Cap cannula which uses standard cannula filters outside the vessel.

Filter Tips

Filter Tips are smaller than cannula filters. They fit on the end of larger diameter sample probes.

USP 232: Heavy Metals and Dissoulution

On 27th December 2013 the USP general chapter 232 was approved and becomes a requirement, with enforcement in 2015. Under this chapter, there is a requirement to show that pharmaceutical companies demonstrate that their compounds comply with strict limits for heavy metal and elemental levels determined by the USP. Previous testing for these is acknowledged to have been poor and this change is aimed to correct that anomaly.

In order to demonstrate that, it is necessary that no part of the dissolution system contributes any heavy metals into the system, and in particular the dissolution filters through which samples are taken.

From June1st 2013 all QLA dissolution filters are tested by ICP-MS and certified to be heavy metal free and therefore suitable for dissolution testing. To further re-enforce the quality of their filters, QLA are introducing their ‘Pure Quality’ label, and all filters labelled as such are traceable not to contain heavy metals. That coupled with their ISO9001 certification awarded by BSI ensure that QLA product remain at the highest quality level possible.

Calibration and Validation

Validation tools are essential in dissolution testing in order to control the many variables that may affect the consistency and reliability of the test results. There are some key variables such as specification (shaft wobble and verticality, basket wobble, temperature. etc.), ASTM (strict regulations concerning verticality, temperature, vibration, position) and the USP (again, regulations - but not as strict).

Key Variables

It is crucial to ensure that the dissolution bath is working as planned and giving precise and reproducible results. Hence it is very important that the bath meets the USP or ASTM regulations. The ASTM variables are stricter as they only on the physical measurement whereas the USP also requires a test using calibrator tablets.

Shaft wobble and basket wobble as well as vibration add to the key variables of controlling hardware variables. Other key variables on terms of hardware control are the rotation, vessel verticality and centering as well as the height of the paddle or basket.

To measure the stability of the paddle or basekt, it is mandatory to use a wobble meter. The wobble meter displays the deviation from the vertical when the shaft is rotated at a slow speed. It uses a special vessel cover that fits inside the top of the vessel. The gauge is attached firmly onto the cover and then places against the shaft or basket - said gauge functions with every dissolution bath where the vessel is accessible during the application.

The vibration meter allows you to quickly assess vibration levels and ensure that low levels are maintained when new equipment is introduced into the lab. Even though it uses digital electronics, it has an analogue needle display, which aids in getting a better feel for the nature of the vibrations - that's why a digital display would not be a good choice here. The vibration meter uses an accelerometer probe which is calibrated to the meter as a matched set. The end of the probe has a custom mounting block compatible with most dissolution instruments.

Further tools to control shaft verticality and vessel verticality, vessel centering, paddle/basket height, rotation and temperature are available also in kits. If you have any problems selecting a proper product or kit, feel free to contact us! Our expert team will be happy to advise you.

Spin Shaft Accessories

Available for Apparatus 1 & 2, the spin on/ spin off shafts offer a quick and easy change between paddle and basket methods without the need to readjust the shaft height. They can be used in any VanKel dissolution apparatus and some of the Distek 2100 and 2500 series.

As for proper usage, it is not necessary to remove the shaft when changing the apparatus as well as there is no need to reset the shaft height or the locking mechanism. The Spin On/Off shafts are manufactured to minimise the risk of cross-threading and guarantee a secure connection.

Concerning care and maintenance, there are similar storage regulations as there are for baskets or calibration tools - do not store the shafts on a desk or put them loosely in a drawer. By doing that, occuring damage such as bending or scratches can not be prevented.

Other Accessories

Furthermore there are various accessories for biodissolution and glassware. Under the category glass accessories you can find:

• volumetric flasks from 500ml to 1000ml
• cylinders such as 10ml tap density or 100ml to 250ml funnel top cylinders
• rotating bottle apparatus
• misc glass accessories such as 100ml to 300ml glass fleaker or 50ml tubes

As for biodissolution we offer the following products:

• caps & covers such as evaporation covers and lower & upper caps for glass vessels
• vessels & sampling tubes for the outer vessel and inner sampling tube