Under Particle Sciences' Analytics Services, we provide a complete suite of drug release assays for a variety of dosage forms ranging from simple tablets to transdermal formulations to implantable devices to nano-particle based formulations. Particle Sciences' cGMP/cGLP Analytic Services facilities are equipped with a wide range of state-of-the-art instrumentation and experienced technical staff to assist you in method development, characterization, and routine and specialized testing. Our facility offers exceptional capabilities in physical property characterization. We are registered with the FDA and DEA licensed for all scheduled substances. Our staff has extensive industry experience to help you in data interpretation and analysis.
In-vitro drug release testing, a measure of release of the active pharmaceutical ingredient (API) from the drug product matrix in controlled laboratory environment, is a key evaluation in drug development and quality control. It involves subjecting the dosage form to a set of conditions that will induce drug release and quantitating the amount of drug released under those conditions. In development, it is an essential test in assessing differences between prototypes, predicting the timeframe of API release, and modeling in vivo behavior. During this phase, in vitro conditions are generally selected to simulate in vivo conditions. In quality control it is used to assess conformance of a batch to pre-determined criteria at time of manufacture and to assess the long-term API release stability. In this use, in-vitro test conditions are chosen to be discriminatory, meaning that they are capable of reflecting a change in API release profile that is related to a change in the drug product. It is an important tool in evaluating drug product performance for most dosage forms and is known as dissolution testing, in vitro release testing, and elution testing.
In vitro dissolution testing of oral dosage forms measures the dissolution rate of an amount of drug substance going from the solid state into solution per unit time under standardized conditions. The goals of a dissolution test include prediction of bioavailability (a surrogate parameter of the therapeutic efficacy), indication of the robustness of the dosage form (drug product safety) and implication of variations in the manufacturing process (which may have a critical influence on performance). USP <711>711> describes the apparatus types and procedural recommendations for testing immediate-, extended- and delayed-release dosage forms. Nomenclature for compendial apparatus for dissolution testing includes USP 1 baskets, USP 2 paddles, USP 3 reciprocating cylinders, USP 4 flow through cell, USP 5 paddle over disk, USP 6 cylinders and USP 7 reciprocating holders. In an attempt to mimic in vivo conditions, the choice of apparatus and method parameters such as medium composition, pH and sampling frequency vary depending on the dosage form and overall purpose of the test. Dissolution is commonly applied to tablets, capsules, suspensions, ointments, creams, suppositories, transdermals, implants, drug eluting stents, medicated gums, and has potential applicability with alternative formulations such as oral and injectable nanosuspensions.
In vitro release of API from topical and transdermal products, and subsequent permeation through a membrane, can be tested in a vertical diffusion cell (i.e. Franz diffusion cell). In this apparatus, formulation is applied or put in contact with a membrane that is in contact with a receiving medium. The receiving medium is sampled as a function of time and API is quantitated to determine a permeation/flux profile. Membrane materials include synthetic polymer, cadaver or animal skin, and tissue constructs. The choice of membrane is driven by the purpose of the test (i.e. development vs. quality control) and robustness of the model. This technique is applicable not only to externally applied topical formulations, but also to products that deliver via the vaginal, rectal, buccal, or nasal routes.
The release of a drug from an implantable device can be assessed in -by subjecting the device to soaking or stirring in a suitable medium, usually with episodic medium exchange. Medium is sampled periodically for quantitation to establish an elution profile. Elution testing can be performed with set periodic medium exchanges (i.e. daily) or with medium circulating around/through the device (i.e. flow-through apparatus). The choice of medium, test volumes, and exchange frequency depend on the nature of the device. The conditions used for elution are driven by the purpose of the test, with simulant conditions being used primarily during development and more robust sink conditions being used as quality control tests.