Problem areas

Weaknesses of Paddle Method

 Problems with floating dosage units products.

 Use of spiral for holding capsules is subject to variability with operators.
 The phenomenon of cone formation that results from nondispersion of disintegrated tablets can lead
to nonreproducibility of test.

Weaknesses of Basket Method

 Poor mechanical stability.

 Hindered visual inspection.
 Disintegration-dissolution interaction (slower disintegration keeps the dosage unit in a site of higher
agitation, thus increasing dissolution).
 Poor homogeneity of the bulk fluid due to insufficient stirring or agitation.
 Sensitivity against external vibration, eccentricity, and the presence of baffles such as thermometer
or sampling tube.
 Inconvenience for cleaning the set-up after testing.

Drug Information Journal, Vol. 30, pp. 1045?1054, 1996 0092-8615/96

Calibration Troubleshooting Tips

There are many factors that will cause a dissolution analysis to give incorrect or errant results. Most
dissolution apparatus will not pass calibration unless all conditions are optimal in the apparatus, the
standards, the media, and the calibrator tablets. Therefore, it is possible to narrow down all possible causes of
failure to calibrate to only a few conditions.

 1. Deaeration of medium

Improper deaeration is the most common problem in dissolution analysis. Heat the media to 41C. Vacuum
filter through a 0.45-um filter into a 4 liter vacuum flask, stirring with a magnetic stirrer. Continue to draw a
vacuum and stir for an additional 5 minutes. When done properly, this process will eliminate almost all
dissolution problems. Media should be deaerated immediately before use. Gently transfer the medium
directly to the vessel. Do not introduce air into the medium. Reaeration occurs within 30 minutes. However,
excess air only occurs after 20-24 hours.

 2. Vibration and mechanical problems

Vibration of the system while appearing insignificant can affect such factors as shaft perpendicularity, head
coplanarity, and tension on the drive belt, centering and operation condition of the gear plates. To minimize
vibration effects, the dissolution equipment should be on a stable bench or table. Other mechanical
equipment using fans, pumps or other vibration sources should be removed from the area or isolated in some
other way. The Bulldozer effect has been shown to give higher results in prednisone. Trains, air conditioning,
pumps can cause vibration,

 3. Tablets----

The calibrator tablets should be stored in the original containers in a dry place. Avoid excess humidity. Use
the tablets immediately on removal from the container. Do not put the tablets out while waiting to start the
test.
4. Reference Standard

Use the current lot of USP reference standard and follow any drying instructions on the label.

 5. Filtering

Do not centrifuge sample. A separate clean dry filter should be use for each sample and the standard.

 Here are the results of some past variability studies done on excess in dissolution on calibrator tablets.

Variable Maximum Allowable* Effects of excess Method of control *Not all of these
are compendial
Wobble 1.0 mm (4-6%) replace shafts
requirements.
Vibration 0.1 mil. displacement @ vessel 5-10% Eliminate source Reference:
Alignment 1.5Degr. to perpendicular 2-25% Adjust alignment Hanson's
Centering 2mm (2-13%) Adjust centering Handbook of
Dissolution testing:
Agitation Rate 4% Linear belts, gears
2nd edition
Dissolved Gas Deaerated +/-50% deaerate media Pharmacopeial
Media pH varies (usually +/-0.05pH) 10% check buffers, pH meter Forum: Volume 20,
Evaporation none Linear use evaporation covers Number 6
Temperature +/-0.5C Linear Monitor temperature
 
Flow no interference ?  remove resident probes