Poor Solubility in Early Drug Development: Evaluating the Right Formulation Approach
Poor solubility in early drug development
Poor aqueous solubility remains a common challenge in drug development. Limited exposure and increased variability can make early pharmacokinetic (PK) results difficult to interpret, particularly when formulation performance is influencing what is observed.
For development teams, the question is therefore not simply whether a molecule is poorly soluble, but which formulation approach is most appropriate for that particular molecule, dose and stage of development.
Understanding the molecule first
At Codis, formulation development starts with understanding the characteristics of the API and the specific challenges those properties present.
Physicochemical characterisation, solubility assessment and an understanding of the intended dose and study requirements can all help inform which formulation technologies should be investigated.
Importantly, there is no single formulation strategy that is appropriate for every poorly soluble molecule.
Depending on the characteristics of the API and programme requirements, potential approaches can include:
Amorphous solid dispersions
Lipid-based formulations
Particle-size reduction
Cyclodextrin complexation
The challenge is determining which approach, or approaches, are worth progressing.
Turning formulation science into practical decisions
Codis brings formulation development, analytical capabilities and drug product expertise together to help development teams evaluate these options.
Rather than selecting a technology at the outset, relevant approaches can be assessed in parallel, allowing decisions to be based on the behaviour and requirements of the molecule.
The Codis white paper, Codis Rapid Screen: Transforming Poor Solubility into a Clear Development Strategy, explores this challenge in more detail, including the considerations involved in selecting and evaluating enabling formulation technologies for poorly soluble compounds.
From technical understanding to Rapid Screen
This scientific approach also underpins Codis Rapid Screen.
Rapid Screen provides a structured way to move from understanding the API to evaluating relevant formulation technologies and selecting an appropriate route for preclinical PK evaluation.
The programme follows four stages:
Study: Characterise the API and understand its physicochemical and solubility properties.
Screen: Evaluate relevant formulation technologies in parallel through targeted feasibility studies.
Select: Compare options based on performance and practical considerations, including stability, dose requirements and developability.
Supply: Provide agreed formulation prototypes for preclinical PK evaluation, supported by practical dosing and handling guidance.
The aim is to provide development teams with a clearer understanding of their formulation options before progressing to the next PK study.
Working with a poorly soluble candidate?
If poor solubility is presenting a challenge in your development programme, talk to the Codis team about your molecule and the formulation approaches available.