Lonza offers PBPK service
Physiologically based pharmacokinetic (PBPK) modelling is a tool that can have a huge impact in speeding up drug development. It simulates a range of physiological factors that have an effect on how an orally dosed drug behaves, flagging up any areas where performance might be expected to be sub-optimal. This allows them to be addressed at an early stage, rather than causing bigger problems later on that might hold up development while a solution is sought.
Solubility is a particular issue, with roughly two-thirds of all small molecule drugs currently in the development pipeline having poor aqueous solubility. If an otherwise promising molecule is to succeed in preclinical and clinical development, this will have to be fixed if it the formulated drug is to have acceptable bioavailability in vivo. The earlier a more soluble form is found that allows target pharmacokinetic profiles to be met, the less likely it is to have a negative impact on timelines and the cost of clinical trials.
While this is a significant example, there are multiple other areas in which PBPK modelling can have substantial benefits in drug development. It can assist in prioritising screening compound libraries for in vivo testing, and can be used in the prediction of starting doses for both animal and first-in-human testing, as well as predicting efficacious doses.
They can support both animal and human risk assessment studies, and even simulate steady state and dynamic drugdrug interactions for regulatory submissions. Insights into food effects can be gained, as can estimations of appropriate dose levels for different patient populations. It can even be used to conduct virtual population PK and PBPK studies and bioequivalence trials.
This is why Lonza is now offering a PBPK service to its clients, which combines ADMET Predictor and GastroPlus PBPK modelling software with a range of in vitro tools, both bespoke and off the shelf. Tools such as biopredictive dissolution testing evaluates how the interplay between a formulation and the properties of the gastrointestinal fluid impacts performance. Including important physiological factors such as GI transit and membrane permeation can overcome the shortcomings of traditional in vitro methods that typically use a single dissolution medium along with non-physiological volumes and dose concentrations.
It can assess a range of formulation problems, such as precipitation and crystallisation, a slow dissolution, and absorption that is limited by solubility and permeability. Armed with this information, techniques to optimise the solid form and the formulation can be applied to maximised its bioavailability.
By identifying potential issues and enabling them to be solved sooner, the effectiveness of the combination offers significant benefits throughout the drug development process. The ability to predict how a compound will behave in vivo is a powerful way to avoid delays, and help it progress into and through the development process more smoothly.
Biocytogen Co Ltd
Draupnir Bio ApS