Dissolution testing is a standardized laboratory method in the pharmaceutical industry that measures the rate and extent a solid dosage form, such as a tablet or capsule, turns into a solution. The process is comparable to a sugar cube dissolving in tea, showing how quickly the solid breaks down. This analysis provides information on how a drug is released from its delivery system under controlled conditions.
The Purpose of Dissolution Testing
A primary function of dissolution testing is to ensure quality control in pharmaceutical manufacturing. The test assesses batch-to-batch consistency, verifying that each production run meets established release specifications to ensure predictable performance. If a manufacturing error produced a batch that dissolves slower than intended, it could impact the medication’s performance.
The test is also an indicator of a drug’s potential bioavailability, which is the rate and extent the active ingredient is absorbed by the body and becomes available at its intended site of action. The test is designed to predict how the drug will behave after ingestion. For these reasons, regulatory agencies like the U.S. Food and Drug Administration (FDA) require dissolution testing for many solid oral drugs.
The Dissolution Testing Process
The procedure for dissolution testing is standardized to ensure results are reproducible. It involves a laboratory apparatus, with several designs recognized by the United States Pharmacopeia (USP). The most frequently used are the basket apparatus and the paddle apparatus, each consisting of a vessel containing a specific volume of a liquid known as the dissolution medium.
This medium is a solution designed to simulate human bodily fluids, such as those in the stomach or intestine. The chemical composition, an acidic or phosphate buffer solution, can be adjusted to mimic different physiological pH levels. During the test, the medium is heated and maintained at 37°C (98.6°F) to replicate the human body’s internal temperature.
Once conditions are set, the tablet or capsule is placed in the apparatus. For the basket method, the dosage form is held in a small rotating wire mesh basket, which is useful for capsules or dosage forms that float. In the paddle method, a rotating paddle stirs the medium after the tablet has sunk to the bottom. The stirring speed is controlled throughout the test, and at predetermined intervals, small samples are withdrawn and analyzed to determine the concentration of the dissolved drug.
Interpreting Test Results
The data collected from periodic sampling is used to generate a dissolution profile. This profile is presented as a graph that plots the percentage of the drug dissolved against time. For immediate-release products, this graph shows a gradual increase that levels off as the drug fully dissolves, within 30 to 45 minutes.
For a drug batch to be considered acceptable, its dissolution profile must meet predefined specifications known as acceptance criteria. These criteria define the amount of drug that must be dissolved by a certain time point. A common specification is that 75% or 80% of the drug must be dissolved within a specified time, such as 45 minutes, based on batches that have demonstrated proper clinical performance.
Dissolution profiles are also used for the approval of generic drugs. A generic manufacturer can demonstrate its product is bioequivalent to a brand-name drug by showing their dissolution profiles are similar. If the generic version dissolves at a comparable rate and extent across various simulated conditions, it provides evidence that it will perform similarly in the body, which can reduce the need for extensive human clinical trials.