Vibration and Dissolution

Dissolution is a highly-controlled sample preparation technique for pharmaceuticals.  It is designed to determine the rate of release of drug from a formulation, and should not be biased based upon the dissolution unit being used.  Alignment of the dissolution unit is one critical element of ensuring that the dissolution unit is creating an appropriate environment for consistent drug release, but there are other factors which can impact the dissolution.  The three most critical issues not related to alignment are vessel geometry, media deaeration, and vibration.  Of these three, vibration is the least understood and has no tolerance associated with it.

Vibration can have very significant impacts to dissolution results.  Usually, disintegration will lead to higher and more variable results - especially with Apparatus 2 paddles.  Vibration, at times, can lead to lower results in Apparatus 1 baskets by shaking drug powder out of the basket and letting it drop to the bottom of the vessel which is relatively unstirred.

If you review requirements pertaining to vibration in the USP, FDA, ASTM, and other dissolution guidances you will find that the dissolution unit should have "no significant vibration".  This is, unfortunately, not very helpful. 

Why isn't there a limit set for vibration?  The reason is that vibration is a very complex measurement - it is made up of displacement, frequency, velocity, and acceleration.  Vibration occurs in the x, y, and z dimensions as well.  Vibration can be steady, or intermittent.  Vibration can be higher in one place than another on the dissolution unit.  The number of variables involved in vibration makes it very difficult to determine which measurement(s) and location(s) to measure.

What should a dissolution lab do in regards to vibration?  The most important thing is to ensure that there is "no significant vibration" prior to beginning each dissolution test.  This could be done with a vibration sensor such as the one on the Agilent 280-DS...or it can be done simply by placing a couple fingers on the dissolution vessel plate and lab bench.  You should feel very little vibration like a mechanical hum.  If you feel anything beyond this, it would be a good idea to investigate the potential source of the vibration and deal with it.  Listening to the dissolution unit can also be helpful to determine potential sources of vibration such as a worn out heater, skipping drive belt, etc.

Vibration come come from several sources - the dissolution unit itself, heater/circulator, other equipment in the lab, or something else in the environment.  If you feel vibration, determine which is/are the sources leading to the issue.

Dissolution unit - misaligned or worn drive belt, heater circulator, under-filled water bath, worn spindles, etc. are all potential causes of vibration on the dissolution unit

Other equipment in the lab - Shakers, tappers, stereos, sonicators, and other equipment such as in the header photo are all potential sources of vibration and shouldn't be near the dissolution unit.

Lab environment - Inadequate lab benches, heavy traffic, slamming carboys, etc.

In addition to checking vibration with each run, I would also recommend taking periodic measurements of the vibration of a dissolution unit and trending vibration results over time.  The Agilent 280-DS software has a built-in trending tool able to look at such trends.  If you find that a dissolution unit has had an increasing level of vibration between measurement intervals, this is usually an early indicator that a belt, spindle, heater, etc. may need service/attention in the future - and you can perform maintenance or repairs before the unit leads to a failure.

Vibration is a major topic of interest in the dissolution community, and one of major importance.  A plan for measuring and minimizing vibration in the dissolution lab is very important for performing meaningful and reproducible dissolution runs.