In a recent publication from USP it is concluded that,

“Apparatus 1 results are stable over time. Those in Apparatus 2 show a decrease over time in the geometric mean but show no trend in variability”.

If all things being equal for testing except differences in apparatuses used, then is it not obvious that instability in results would reflect the instability of Apparatus 2? The conclusion from the USP supports the observation/results reported in the literature regarding poor performance of Apparatus 2. This poor performance in testing is a reflection of poor hydrodynamic environment within dissolution vessels as described extensively in literature. Thus, the use of Apparatus 2 would require caution.

 USP calendar shows an entry of a planed webinar to address the problems in the dissolution testing area. USP is requesting submission of questions so that issues and concerns may be addressed in this regard. The following are some suggested questions/concerns which USP may consider addressing during the webinar or later.

1. USP usually recommends the use of Paddle and Basket apparatuses for drug dissolution testing as a first choice. Are there any documented reasons (evidence) for these choices showing their superiority compared to other apparatuses? How have these apparatuses been validated as appropriate dissolution apparatuses to evaluate pharmaceutical products for human use?
2. Commonly, as a general practice, USP suggests experimental conditions for individual products (monographs) to establish their drug dissolution characteristics. This aspect is also described in more detail in the chapter <1092>. The practice Continue reading →

It is important to note that the emphasis is on the “practice” and not the drug dissolution testing itself. A drug dissolution test is an important and extremely useful test and is required for the development and evaluation of pharmaceutical products, in particular tablet and capsule. However, how the test is conducted, which is referred here as the “practice”, is very different from dissolution testing itself. One should keep this difference in mind.  Continue reading →

Hello Vivian:

As suggested, I am posting your response to the above mentioned post, along with an Editorial note from myself. Regards. Saeed

Editorial Note:

To address this response, I would like to make it clear that in my post I was referring to a potentially diminished role in the future. Also, I assume that your comments are reflective of your personal views and not those of the USP or the new Expert Advisory Committee.

Response:

Dear Saeed, I feel I have to respond your recent posting on your website about Changes at USP. Please be sure you have seen the article in the August issue of Dissolution Technologies that gives the make up of the new USP committee. This information in is the USP update with Tom Foster achieving the Beal award. In that article the new members of the new committee are listed. There are five members of the BPC committee that are now on this new committee. They are Mario Gonzalez, Johannes Kramer, Tom Foster, Alan Parr and I. These people were very much involved with the PVT and I can assure you that the work will continue in the new committee and at the USP labs. The USP has published many articles in Pharmacopeial Forum (PF) about the PVT and evaluations of variables using the Prednisone Standard Tablets. Also if you look in Dissolution Technologies (DT), www.dissolutiontech.com back issue there are a plethora of articles on the dissolution variables and the USP Prednisone Tablets. Also in DT we have reprinted many of the PF articles about the PVT and the new criteria. So the “absence of clear information” is not accurate. If you go to the USP website there are many places for information on the subject including the USP Tool Kit on mechanical calibration. As a point of interest, the PF will be available on line for free in 2011.

I was hoping that I could respond on your website but the comments are closed. Please consider posting my reply to you in this public forum.

Best regards, Vivian

9 Yorkridge Trail
Hockessin, DE 19707 USA
Tel. 302-235-0621
Fax 443-946-1264

vagray@rcn.com
www.vagrayconsulting.net
www.dissolutiontech.com (now searchable, check it out)

Provided are links to two recent articles, written by Dr. L.T. Grady who was Vice President and Director of USP Division of Standard Developments (1980-2000), from the website of Dr. T. Layloff, who later himself was Vice President and Director of USP Division of Standard Development. 

The titles of the articles are “Letter on the Adequacy of Dissolution Testing” and “Perspective on the History of Dissolution Testing”.

The contents of the articles are quite revealing, indicating that the high variability in dissolution results and their poor link to the product quality were well known within USP.

Current practices of drug dissolution testing require that the experimental conditions, such as medium and its volume and apparatus and its associated stirrer rotation speed, be established for each test product to achieve certain ‘expected’ dissolution characteristics or results. In reality, however, the purpose of dissolution testing should be to determine potentially unknown dissolution results reflective of a test product based on its formulation and/or manufacturing attributes. For appropriate testing, in particular for comparative purposes, the experimental conditions must be the same or consistent from product to product i.e. product independent. This article describes a newly developed spindle, known as crescent-shaped, which can easily be installed in the vessel-based dissolution apparatuses (basket and paddle) to provide a product-independent dissolution testing approach for improved drug dissolution assessments. The new spindle provides an improved stirring and mixing environment, leading to better characterization of pharmaceutical products. The use of the crescent-shaped spindles offers additional significant advantages over the current practices, such as: (1) allows analyses using a single method, compared to hundreds as currently required, for both immediate and extended-released products having the same or different active ingredients; (2) provides improved dissolution characteristics of products by avoiding false slow release properties for fast release type products; (3) simplifies testing by avoiding the necessity of developing separate QC and bio-relevant dissolution methods; (4) provides a rugged testing environment free from common sensitivities, in particular to de-aeration and vibration effects. (Link to the article).

The upcoming 1-day course will cover this topic in further detail.