A New Crescent-shaped Spindle for Drug Dissolution Testing—But Why a New Spindle? (Link).

Crescent-shape spindle: Facts sheet (Link)

Advantages of using the crescent shape spindles for drug dissolution testing (Link)

The following links are for the short video clips demonstrating comparative operations of the paddle and the crescent-shape spindles.

Using a disintegrating tablet: Paddle and Crescent-shape spindle

Using a non-disintegrating tablet: Paddle and Crescent-shape spindle

Note: Dimensions may appear slightly distorted

On-site training/demonstration can be arranged. Post-graduate/doctoral fellows who are interested in using the crescent-shaped spindles for their on-going research projects may request samples.

For further information and purchase inquiries please contact by sending an email to (sales@pharmacomechanics.com) or call at: 1-613-797-9815.

Commonly pharmaceutical products are evaluated and developed based on four “quality” parameters/measurements: (1) Identity, to show that a product contains the expected drug; (2) assay, to show that a product contains expected amount of drug (dose); (3) Content Uniformity (CU), to establish that the dose or drug content in each unit varies within an expected range; (4) Dissolution/release, to show that the drug will be released from the product in an expected manner. All these tests are simple chemical tests based on solvent extractions, i.e. the drug is extracted from the product and measured using any of the quantitative techniques such as spectrophotometeric or chromatographic.  For complete article, click here.

Certainly, current practices of drug dissolution testing appear so. Let me explain …

For any analytical technique, there are two basic requirements which it must meet to be considered as an appropriate technique. (1) The technique must be able to provide relevant results and, (2) the technique must be able to provide reproducible results with acceptable variance. In terms of both requirements, dissolution testing would not meet the criteria of an appropriate analytical technique.

For a technique to provide relevant results, it must clearly be linked to a useful and measurable property of the sample. At present, dissolution testing is not linked to a property of the sample (drug product). Currently, it is quite often described as a tool for monitoring the “quality” of drug products, which is similar in concept to monitoring the “quality” of a person, a vague and undefined objective. Therefore, if the objective is vague and undefined then it is not possible to obtain relevant results. Thus, the outcome becomes testing for the sake of testing.

With regard to reproducibility, again, dissolution testing does not meet appropriate requirements. In response to the negative concerns often expressed in literature about the observed excessive variability of testing, suggestions are often made to tighten specifications and/or other controls, e.g. vessel diameter/curvature, removal of all sources of vibration, de-aeration, training of the analysts, and many more. The question would still remain, what should be the acceptable variations of the test and on what basis? Should the %RSD be 1% or 35% or in between and which value should be considered correct and acceptable? The only way to answer this is through multi-lab performance verification tests, such as USP conducts. Unfortunately, USP does not accept the results from its own studies which show lack of acceptable reproducibility of the test. Other regulatory bodies stopped using such a performance test as it does not SHOW acceptable reproducibility. However, there is continued acceptance of the results from the tests based on the assumption that the technique/test provides an acceptable level of reproducibility. It is not clear how, and on what basis that an acceptable level of reproducibility of the test/technique is assumed? Therefore, how would an analyst determine the reproducibility of the test and be able to differentiate it from the variability of his/her product or results. Thus, until and unless, the variability of the underlying test/technique is not known and established, dissolution testing will remain testing for the sake of testing.

It should, therefore, be kept in mind that if an analyst is expected to use dissolution testing, in particular using the paddle/basket apparatus, it is highly likely that the dissolution results will neither be relevant nor reproducible.

Drug dissolution test as a quality control test: In simple terms, at present a dissolution test as a QC test means conducting a dissolution test as described in a pharmacopeia, in particular USP. If the test meets the pharmacopeial (Tolerances) requirements then the product may be considered a “Quality” product. It is, however, not clear what “quality” the test refers to or to what product property the test is linked to? Therefore, to overcome this lack of objectivity/relevancy, pharmacopeial tests are described as “consistency” tests. Again, it is not clear the “consistency” of which property or parameter the test is refers to?

Dissolution testing during product development: One of the main uses of dissolution testing is to facilitate product development. This use is based on the principle that the tests should be able to provide potential in vivo drug release behavior information. However, this is a commonly recognized fact that currently used dissolution tests generally do not provide in vivo relevant product characteristics. Thus, current practices of dissolution testing at the product development stage appear to lack relevancy and objectivity.    

Practices of methods development: For developing a method one requires a well established and accepted reference (product or parameter). In this case, a reference product should be available with known drug dissolution results which are established independently. As there is no reference product with known dissolution results Continue reading →

Product development stage: What this really means in simple terminology is the stage where a product (formulation + manufacturing process) is developed to show that it is capable of releasing (dissolution) the drug and providing desired drug levels in humans. The drug release characteristics of the product are usually established based on human studies which are commonly known as bioavailability/bioequivalence (BA/BE) studies. However, one requires a simpler in vitro method to screen test products (especially multiple combinations of formulations) to select some (usually one or two) for BA/BE studies.
 Drug dissolution test: This is the in vitro test which is used for this purpose i.e., to evaluate potential release characteristics of different products (or formulations). It is, therefore, very important to note that at this stage a formulator must have access to a dissolution method which is capable of reflecting potential in vivo drug release (dissolution) characteristics in humans. This method must already be developed and validated using other well characterized product(s) for human use. In the literature, it is often described that a specific dissolution method be developed at this stage for the particular test drug/product. However, such a practice is scientifically invalid, as a method can only be developed using a product with well established dissolution characteristics. At the product development stage a dissolution test is applied not developed. This is a very important concept, often over looked and should, therefore, be kept in mind. Continue reading →

For clinically relevant tolerances, perhaps the most important consideration is that the tolerance should reflect consistent and reproducible delivery of an expected dose (amount of the drug) to the patient. Commonly, dosage or strength of a tablet/capsule reflects the expected amount of drug to be released or delivered.  Therefore, for clinical relevance, the amount of drug to be released is fixed, i.e. 100% (at least on average). The only variable which needs to be determined is the time, i.e., how long would it take for the drug to be released. For IR products, this duration of drug release is usually an hour or less. However, in exceptional cases, based on experimental evidence, this time duration may be adjusted as required.

The setting of tolerances, therefore, should be based on the duration of time required for the release of all drug present in the product.

It is to be noted that at present, tolerances are set (e.g. see USP) based on two parameters (values) i.e. amount of drug released at a certain time.

The amount (%age of drug) released is often referred to as the Q-value. Although, the Q-value is set based on the product behavior at the product development stage, it is still chosen arbitrarily rather than based on any scientific/clinical relevance. It is not clear why this Q-value is chosen arbitrarily and set at less than 100%, usually 80% or lower, when it should be 100%. The practice of setting tolerances at 80% or less may not be clinically relevant and require reconsideration.

In short, clinically relevant tolerances should only be based on the time duration, i.e., how long would it take for 100% of the drug to be released from a product.