Drug Dissolution Testing

I’ll be giving two talks on drug dissolution testing at the Informa Conference on Bioavailability / Bioequivalence, Dissolution and Biowaivers, 23 – 24 May 2012, Continental Zara Hotel, Budapest, Hungary.  http://www.informaglobalevents.com/event/beba12

If you are attending the conference, I will be very happy to discuss topics of your interest before or after the presentations. Please, let me know by sending an email to moderator@drug-dissolution-testing.com

Considering the flaws of poor hydrodynamics of the most commonly used apparatuses, paddle and basket, it is very well established that these apparatuses are not qualified and validated to provide relevant and reproducible dissolution results. Therefore, it is natural that people are seeking alternatives. The vessel based apparatuses using the crescent shape spindle provides such an alternative. The next obvious question would be, are such apparatuses qualified to be used as dissolution testers? Also, have these been standardized? The answer to both questions is yes, as explained below. please click here for complete article

The purpose of a dissolution tester is to test a tablet/capsule product for its potential dissolution characteristics in the human GI tract. In general, it is now well recognized that the currently used dissolution testers, in particular paddle and basket, do not provide such dissolution characteristics. In fact, they cannot provide dissolution characteristics because of the flaws of poor product/medium interaction within the apparatuses. Therefore, these apparatuses cannot be qualified and/or validated as dissolution testers and thus cannot be used for the development and evaluation of the products.

The practices of the past many years have been to keep using these apparatuses for product development and evaluation (isn’t this bizarre?) with a change/twist in the objective of dissolution testing by calling it a quality control test. However, how does one link the dissolution test to the quality of the product, when it will require its link to the dissolution characteristics in vivo, i.e., human GI tract? Oops, there is no link here, as stated in the paragraph above. Read the rest of this entry »

These apparatuses:

1. Lack scientific merit and support. Experimental studies have shown that they will provide highly variable and unpredictable results because of poor product/medium interaction.




2. Cannot be qualified/validated using commonly used industry wide practices of qualifications for analytical instruments. In particular, they do not meet the requirements of design qualification (not fit for intended use) and operation qualification (cannot be qualified using a reference product).




3. Require meeting undefined and unqualified requirements such as de-aeration of the medium and control of vibration in and around the equipment.




4. Require drug and/or product dependent experimental conditions. Therefore, it will not be possible to know whether dissolution characteristics are a reflection of the products or of the experimental conditions used.




5. Do not differentiate between IR and ER products. The analyst must first know what type of release/dissolution to expect from the product and then use the experimental conditions design to provide the presumed released/dissolution characteristics.




6. Are routinely used for evaluating drug products for human use (e.g. pharmacopeial testing). However, they have never been validated to demonstrate that they can provide bio- or physiologically relevant results.




7. Are often used for quality control, and to check lot-to-lot consistency, purposes. However, a link of these apparatuses, and associated experimental conditions, to the quality of a product, and consistency thereof, is unknown or undefined. The only criterion used for this purpose is that the dissolution results must meet some arbitrary standards/tolerances. If the criterion is not met, it is assumed that the products may be of substandard attributes.




8. Are expected to provide discriminatory tests which should be capable of showing formulation/manufacturing differences among products and/or batches. On the other hand, it is a well known fact that these apparatuses frequently provide discriminatory results lacking any physiological significance or consequence.




9. Do not simulate in vivo or physiological environment (stirring and mixing) thus one cannot develop bio-relevant tests.




10.   Require tolerances be set lower than potency and content uniformity values, thus, results will reflect inaccurate and inappropriate quality of perfectly acceptable products.

Considering the above mentioned deficiencies, results obtained using these apparatuses can easily be questioned/challenged for their validity and relevance.

It is a well established fact, and often a regulatory requirement, that one has to demonstrate that an apparatus is capable of providing the intended and expected outcome. A simple and common example of this requirement is calibration of a laboratory weighing scale or balance. Initially when a balance is purchased, and then occasionally thereafter, it must be calibrated against reference weights to show that the balance can provide accurate weights of the references. If the balance does not perform as expected then it has to be adjusted accordingly. please click here for complete article