IVRT method development and test conducted at Zyleris are in full compliance with FDA
IVRT method development
IVRT method development process at Zyleris:
- Membrane selection - membrane binding test (static and diffusion test), compatibility and "wettability" of membrane by the formulation. Even both hydrophobic and hydrophilic membrane pass the binding test, the membrane must be compatible and wettable by the formulation in order to achieve efficient release of an API.
- Receptor medium selection - API release, and solubilization (thermodynamic and kinetic), API stability, back-diffusion of receptor ingredient(s), membrane stress test in the selected receptor medium.
More often than not, screening of API solubility alone is not enough in selecting a suitable receptor medium. API release from the formulation must be screened as well in order to achieve sufficient release.
- IVRT sensitivity - ability to detect concentration change.
- IVRT specificity - proportionality and linearity of API release.
- IVRT selectivity - ability to detect inequivalent product.
- IVRT discriminality and robustness.
Zyleris is highly experienced in development of IVRT methods for topical products. We have successfully developed IVRT methods for challenging formulations, such as, e.g., , formulations containing high API concentrations or having fast API release, ointments containing hydrophilic APIs, combination products, particularly when the API combination contains a lipophilic and hydrophilic API, and foam formulations.
In addition, Zyleris have also successfully developed IVRT method for ophthalmic suspensions.
- In our HT Franz Cell system, entire content of the receptor medium will be replaced with a fresh, pre-incubated batch at each time point. This unique sampling (shuttle-sampling) mechanism ensures that the required sink-condition can be always well-maintained. This makes selection of a receptor medium easier, which is particularly beneficial for IVRT method development of a "challenging" formulation. Since the receptor medium is only needed to solubilize the API accumulated in short time intervals (e.g., 1-2 hours), rather than throughout the entire experiment (e.g., 6-8 hours), this system allows greater freedom in selection of a receptor medium for IVRT method development.
- Our high-throughput Franz Cell platform makes it possible to simultaneously compare multiple prototype formulations to a reference listed drug (RLD) - accelerating your formulation and process development.
- We are capable of running multiple prototypes, or multiple batches of prototypes and RLDs simultaneously, minimizing inter-day data variation.