The single-stage biorelevant dissolution test is conducted using the USP 2 Apparatus with a paddle speed of 75 rpm and a temperature of 37 °C. For FaSSGF (fasted state simulated gastric fluid), a vessel volume of 250 mL is used, while FaSSIF (fasted state simulated intestinal fluid) and FeSSIF (fed state simulated intestinal fluid) require a volume of 500 mL.
Sampling occurs at specific time points: 5, 10, 20, and 30 minutes. If slow dissolution is evident, subsequent samples are taken every 30 minutes until a plateau is reached. In cases where a plateau is achieved within 10 minutes or less, additional early time points are recommended.
Dosing involves mimicking the human dose, potentially necessitating the addition of multiple dose units. In this context, a single capsule of the test product (no brand name specified) is used. To ensure robust results, a minimum of 3 replicates per experiment is performed, with many partners opting for 6 replicates.
Sampling and analysis follow a consistent methodology. Manual sampling using a 5 mL syringe is employed, with an approximate 0.5 mL analysis sample extracted. These samples are then subject to suitable analytical methods for the specific drug. A filter is used to separate undissolved particles from dissolved ones, with drug adsorption on the filter limited to 2%. If higher adsorption occurs, this is clearly reported. Filters with a pore size of 0.45 μm and a diameter of 25 mm (such as PTFE, GHP, or glass fiber filters) are common. Pre-filters are advised if excessive undissolved excipient or drug is present.
Furthermore, when utilizing a vessel volume of 250 mL within a standard 1 L dissolution setup, prudent caution should be exercised concerning the implementation of bathless dissolution vessels, primarily due to potential heating zone intricacies. It is noteworthy that the reduced volume configuration positions the paddles in close proximity to the medium's surface, introducing potential variability in sampling methodologies. Such considerations underscore the need for meticulous adherence to the prescribed protocol to ensure the fidelity of biorelevant dissolution testing outcomes.
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Resource Person: Prakash Amate
