Developing validating dissolution procedures

Dissolution is the primary pharmaceutical test that is designed to probe the performance of dosage forms.

From its beginnings in the middle of the twentieth century to address some serious issues with products on the market [1], the scope of application has grown to include use as a tool for formulation selection during product development and as a tool to enable waivers of bio-studies [2,3] under certain circumstances.

Naturally, a dissolution test should be well suited to its intended purpose, but the purpose may be different depending on the circumstances.

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delayed release products have a fairly specific dissolution protocol described in the United States Pharmacopeia).

Solubility is a key parameter for dissolution, so solubility should be determined empirically at several p H values across the physiological range (p H 1 to 7.5) ().

There are many ways to conduct this experiment; one useful method is to put excess drug into a 30 m L vial with compendial buffers over the p H range and store them at 37°C or room temperature for 24 hours, with gentle agitation such as a rocking shaker.

In an ideal world, a single dissolution test might be able to address all three of these needs, but this is probably not realistic from a practical perspective.

There is a growing interest on the part of regulators to see ‘clinically relevant dissolution specifications’ [5], that is, specifications that can be linked to the performance of the drug product , but we have a long way to go in this arena.

Starting with the QC dissolution test, the first order of business will be to collect information. Is it intended to be an immediate release, extended release or delayed release oral product, or something different?

This will help to identify the time scale for the dissolution test, and could influence other parameters of the test (e.g.

In order to successfully develop a dissolution test, we should first identify the Analytical Target Profile [4]: purpose of the test, expectations for the data generated, and how it will be decided if the test is meeting its intended purpose.

A typical ATP for a quality control dissolution test is shown in Subsequent steps typically include learning about the solubility of the drug, selecting the dissolution test conditions and developing an analytical procedure to measure the dissolved drug in solution.

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