Case Study
Improving Oral Bioavailability of a
Poorly Soluble Molecule
A BCS Class II compound with promising efficacy was limited by low and variable exposure. We applied predictive modelling and formulation engineering to enable clinically viable performance.
Development pathway
The Challenge
A molecule constrained by its
own delivery limitations
The molecule demonstrated strong pharmacological potential but was constrained by poor aqueous solubility and inconsistent oral exposure.
Preclinical studies revealed significant challenges that threatened the programme’s clinical viability.
- High variability in gastrointestinal absorption
- Suboptimal systemic exposure relative to efficacious targets
- Lack of correlation between dose and pharmacokinetic response
Clinical implications
Why Conventional Approaches Were Insufficient
Standard strategies
fell short
Standard formulation strategies — including micronisation and conventional solid dispersions — failed to deliver consistent improvements in bioavailability.
Our Approach
An integrated, prediction-led
development strategy
We implemented a structured approach combining mechanistic modelling with formulation design — anchored to clinical exposure targets from the outset.
Data Integration
Aggregation of physicochemical, preclinical PK, and permeability data. Identification of critical determinants of oral absorption.
Predictive Modelling
Development of a PBPK model to simulate human exposure. Scenario testing across candidate formulation strategies.
Formulation Strategy Design
Selection of a lipid-based delivery system. Optimisation for solubilisation capacity and absorption window alignment.
Iterative Validation
Alignment of in vitro and in vivo performance. Refinement guided by model-informed insights rather than empirical iteration.
Process at a glance
Solution Implemented
A nano-enabled lipid-based
formulation platform
A lipid-based nano-enabled formulation was developed to enhance solubilisation and stabilise the drug in the gastrointestinal environment.
Improved dissolution rate under physiologically relevant conditions
Reduced precipitation risk within the gastrointestinal tract
Enhanced permeability and absorption consistency across subjects
The engineering rationale
Lipid-based systems create a solubilised drug environment that persists through the gastrointestinal transit window. By engineering droplet architecture and excipient interactions, we stabilised drug concentration at the absorptive surface — translating directly into improved and reproducible systemic exposure.
Outcomes
Measurable improvements in
translational performance
What Made the Difference
Integration over
iteration
Four principles that distinguished this programme from conventional development approaches.
Early integration of predictive modelling with formulation design — before bench work began, not after.
Focus on clinical exposure targets from the outset — not just in vitro optimisation as an end in itself.
Iterative, data-driven decision-making framework that reduced reliance on empirical trial-and-error cycles.
Alignment across preclinical, formulation, and clinical objectives to ensure decisions were commercially viable.
Where This Approach Applies
Built for complex molecules
and high-risk assets
This methodology is directly applicable to a broad range of development challenges — wherever solubility, variability, or exposure limitations are constraining clinical progression.
Development Process
From data to
clinical readiness
Data aggregation
Predictive modelling
Formulation strategy
Validation & optimisation
Clinical readiness
Details have been generalised to preserve client confidentiality whilst accurately representing the scientific and strategic approach applied throughout this programme.
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