XenoGesis can develop basic formulations in-house and also offer a state-of-the-art dosage technology and product forms service with one of our recommended CDMO partners.
Pre-formulation screening by Contract Development and Manufacturing Organisations (CDMOs) focuses on the physicochemical characteristics of an active pharmaceutical ingredient (API), such as particle size analysis, solubility screening, pH-based stability and amorphous content. There is a strong focus on the screening of excipients ahead of generating either simple solutions/suspensions or more complex formulations. The evaluation may also include stability and forced degradation studies.
These screens do not review the biological characteristics of the compound. If the compound has serious DMPK liabilities, such as a high gastrointestinal or liver clearance, then formulation strategies may not be sufficient to overcome these limitations and it may not be possible to achieve the human exposure required for efficacy.
It is not uncommon for clients to commit to a complex formulation strategy in order to enhance oral bioavailability, be disappointed in the performance of the formulations and only then consider whether the biological attributes of the compound might contribute to poor exposure, after much time and money has already been spent.
XenoGesis provides a ‘pre-formulation (exposure) health check’ to determine whether the API possesses any intrinsic biological liabilities prior to starting a formulation project. This service includes:
- review of DMPK data package
- identification of any data gaps
- provision of next step recommendations where gaps exist
- backfilling/data generation to fill gaps
- review of the initial or predicted bioavailability
- physiologically based pharmacokinetic (PBPK) modelling and prediction of absorption using GastroPlus®
- recommendations for formulation strategy
Generation of formulations
XenoGesis works with carefully selected CDMOs who can provide a range of formulations for evaluation. These include:
- amorphous solid dispersions (e.g. spray drying, hot melt extrusion)
- API particle size reduction (e.g. micronisation, nanomilling)
- lipid/surfactant systems (e.g. SEDDS, SMEDDS)
XenoGesis can evaluate formulations provided from your CDMO partner of choice.
Evaluation of formulations
Upon receiving the formulations, XenoGesis will:
- determine the IV parameters of each formulation in pre-clinical species
- determine the bioavailability of each formulation (relative or absolute if IV data is obtained)
- undertake PBPK modelling
- undertake pre-clinical modelling to assist clients to choose the most appropriate formulation for human studies
- provide an estimate of efficacious dose and dosing regime
CDMO partners and consultants
XenoGesis works with carefully selected trusted CDMO partners and consultants who can provide a range of formulations for evaluation.