Dissolution Testing
The Food and Drug Administration (FDA) requires dissolution testing to ensure continuous drug product quality and performance of controlled-release and extended-release products. This testing is performed during product development, batch release, and stability studies to verify that the release rate of the active pharmaceutical ingredient meets established specifications. Variability in release rates between batches can pose a significant risk to patient safety and may result in inaccurate dosing, reduced drug efficacy, and adverse reactions.
Drug absorption is formulation-dependent and influenced by the active pharmaceutical ingredient's release profile. The FDA uses a biopharmaceutics classification system (BCS) to categorize drug substances based on their aqueous solubility and intestinal permeability, which includes:
- Class 1: High Solubility – High Permeability Drugs
- Class 2: Low Solubility – High Permeability Drugs
- Class 3: High Solubility – Low Permeability Drugs
- Class 4: Low Solubility – Low Permeability Drugs
The BCS framework sets dissolution expectations and can support biowaivers for oral drug products. However, the FDA does not set a universal dissolution standard for each drug class. Instead, dissolution specifications are generally derived from United States Pharmacopeia (USP) monographs, when available, or developed and validated based on specific drug products. If there is no existing standard for a certain drug profile, compounders can establish their own specifications. Validation of the dissolution test method is required to support specifications and acceptance criteria. The dissolution characteristics should be based on the pH, solubility, and pharmacokinetics of the drug to ensure bioequivalence for future batches while also adhering to acceptable dissolution limits.
According to the Center for Drug Evaluation and Research, once a dissolution specification is set, the drug product should comply with that specification throughout its shelf life.
Dissolution Test Methods
Dissolution testing uses various apparatus methods based on USP 711. The basket and paddle methods are among the most commonly used for testing a wide range of drug products. In these methods, the solid dosage form is placed into a dissolution instrument containing six vessels, all maintained at a specific temperature. The paddle rotation speed and duration are controlled to simulate gastric or absorption conditions. At predetermined time intervals, samples are drawn from each vessel.
These filtered samples are then analyzed to quantify the percentage of active pharmaceutical ingredient (API) released from the dosage form, using UV spectrophotometry or HPLC. This allows for a precise assessment of drug release profiles.
Overall, dissolution testing is a critical component of quality testing programs. This testing provides valuable insights into the absorption rates, helps predict the release behavior of active pharmaceutical ingredients, guides the selection of the most effective formulations for optimal therapeutic outcomes, and ensures consistency throughout the production process.
For more information on dissolution testing, contact ARL Bio Pharma at 800-393-1595 or info@arlok.com
Resources:
- USP 711 Dissolution
- FDA Guidance for Industry Dissolution Testing and Acceptance Criteria for Immediate-Release Solid Oral Dosage Form Products Containing High Solubility Drug Substances
- FDA CDER Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms