Dissolution

So-called dissolving profiles are also possible. For this purpose, the active substance content in the dissolution medium is determined at several time points and displayed as a function of time.

The results obtained can be used to indicate batch-to-batch consistency and consistent efficacy of the product. In addition, batch homogeneity, compliance and stability can be tested.

The dissolution rate is usually measured for the following dosage forms:

• Solid dosage forms (e. g. capsules, tablets, medicated chewing gums)
• Pure solid susbstances / active substances in preparations presented as powders or granules (apparent dissolution rate)
• Lipophilic dosage forms (e. g. suppositories, soft capsules)
• Transdermal patches

The GBA Group is experienced in testing all of the following dosage forms.

Requirements of the pharmacopoeias

The requirements from the following regulations are harmonized:

• USP <711>
• Ph. Eur. 2.9.3
• Ph. Eur. 2.9.42
• Ph. Eur. 2.9.43
• ICH Q4B Annex 7R2

Further requirements:

• Ph. Eur. 2.9.4
• Ph. Eur. 2.9.25

Dissolution testing is described in the pharmacopoeias and various FDA guidelines.

Analytical principles of the dissolution test

The dissolution test can be roughly divided into two sections. On the one hand, sample preparation via the release tester and, on the other, the analytical method for content determination. During development and validation, both sections are finely adjusted to each other in order to achieve optimum results.

Dissolution Part

Like product formulations, the equipment used to dissolve them is highly variable.

The active ingredient is typically released from 6 units in parallel using dissolution equipment. The drug is dissolved under controlled conditions. The basket (Apparatus 1), the paddle (Apparatus 2) and the flow cell (Apparatus 4) are the most commonly used test devices. The solution is withdrawn from the 6-pot apparatus at fixed times followed by determination of the content. By using semi-automatic dissolution systems, sampling can be automated and thus carried out efficiently.

The following instrumentation is available at GBA Group:

• Basket (Apparatus 1)
• Paddle (Apparatus 2)
• Reciprocating cylinder (Apparatus 4)
• Flow-through cell (Apparatus 5)

The instruments used at GBA Group are regularly qualified in accordance with pharmacopoeia requirements and measurements are performed in accordance with (c)GMP quality standards. The instrument pool in the dissolution testing area is very large and there are many redundant systems. This gives you the certainty that there is always an instrument available for your measurements at any time. A total of 10 instruments are available for the basket and paddle method and 2 instruments for the flow cell dissolution tester. By using semi-automatic dissolution systems, sampling can be automated and thus carried out efficiently.

Furthermore, we have experience with complex dissolution tests where, for example, the dissolution is carried out over days and a change of media is required (gastric juice resistant tablets).

Determination of content

The active ingredient content in the dissolution medium can be quantified using different methods depending on the particular task:

• Photometric approaches (UV/VIS)
• Chromatographic approaches (HPLC, UHPLC)
• Rarely ICP-MS, AAS

The GBA Group has redundant systems and a very high level of expertise in the field of content determination. The specialists have many years of experience in the development and testing of analytical methods for content determination.

Dissolution of highly active substances

As a special feature, we offer the service of dissolution tests for highly active substances. The tests are carried out in the laboratory with increased safety levels.

Determination of the similarity factor f2

Would you like to evaluate the similarity of two dissolution profiles? This is no problem. We have experience in this area and can determine e. g. the similarity factor f2 for you.

Validation of the analytical procedure

If you plan to use the measurement results for batch release of the medicinal product, validation of the analytical method is essential. The methods of active ingredient dissolution and content determination, which are finely adjusted to each other during development, are put through their paces in order to achieve trustworthy, correct and accurate results in routine use.

We are happy to carry out the validation of the analytical method. If preferred, we will work with you to plan the necessary tests and send you a draft version of the validation plan and report. This means that you have direct control over the tests carried out at all times and receive regular updates so that you have a continuous overview of the progress of the project.