Drug Elution

Drug release/elution is a test that is needed for any solid oral dosage form (e.g. tablets and capsules) or for any controlled release product (e.g. an injectable containing liposomes), including combination products, such as drug-eluting stents. For immediate release products, it is necessary to demonstrate the most of the drug is released into solution in a relatively short time period, typically less than 1 hour, and that the product will do this reproducibly. For controlled-release or sustained-release product designed to release the drug over an extended period of time to achieve more uniform blood levels of the drug, to reduce the number of dosage units a patient has to take in a day, often resulting in better patient compliance and better clinical efficacy. Usually, USP (United States Phamacopeia) apparatus are used (found in USP monographs <711> and <724>). Apparatus 1 through 4 are described in USP <711> and apparatus 5 through 7 are described in USP <724>.

In the special case of elution of a drug from combination products, the elution may be over an extended period of time, days (antibiotics from hip/knee implants), weeks (drug-eluting stents), or even years (contraceptive devices). In these cases, the blood levels are so low that it is not practicle to measure these levels in order to determine an in-vivo release profile in humans. Often, representative elution media are used to achieve a suitable elution profile similar to that achieved in animal studies. This elution media may be biologically relevant, in the case of serum, or more likely in the case of accelerated methods will not have any biological relevance, using surfactants and possibly organic solvents. Typically, an accelerated method is needed due to the lack of stability of the drug in the media and the necessity to have a quality control method to be able to release the product. This method must be demonstrated to be discriminatory so that any product not having the proper elution charactistics will have a different elution profile and with specification limits appropriately set (more to come on setting appropriate specifications) will fail the specifications and not be released. As with all methods, this method must also be validated for specificity, accuracy, precision, linearity, ruggedness, and robustness. Stability of the drug in the media must also be demonstrated, as well as the solubility of the drug. The solubility is particularly important, since many drugs have very low solubility especially in aquious media. "Sink conditions" must be demonstrated, that is that the highest concentration of the drug in the media does not exceed approximately 1/3 the solubility of the drug in that media.