New CBD Formulation Achieved Higher Blood Levels Than Epidiolex in Rats | Research

The takeaway

A biodegradable self-emulsifying CBD formulation outperformed the FDA-approved Epidiolex in oral bioavailability and peak plasma concentrations in animal testing.

Pharmaceutical scientists, CBD product developers, and those interested in drug delivery technology.

What the researchers found

Polyglycerol-based self-emulsifying drug delivery systems (SEDDS) achieved 3.8% absolute oral bioavailability for CBD compared to 3.4% for Epidiolex, with peak plasma concentrations of 30.6-35.8 ng/mL versus 25.0 ng/mL for Epidiolex.

Why it matters

CBD has notoriously poor oral bioavailability, meaning most of what you swallow never reaches your bloodstream. Better formulations could make oral CBD more predictable and effective, which matters for both pharmaceutical and consumer products.

The numbers in context

CBD payload: 20% w/w. CBD retention in lipid core: 92.95-93.54%. PG-based SEDDS bioavailability: 3.8% vs. Epidiolex 3.4%. Peak plasma CBD: 30.6-35.8 ng/mL (SEDDS) vs. 25.0 ng/mL (Epidiolex).

How the study worked

Three SEDDS formulations using different emulsifier types were developed and characterized through in vitro testing (surface properties, lipolysis, mucus permeation) and in vivo pharmacokinetic comparison with Epidiolex in rats.

What this study cannot tell us

Animal pharmacokinetics do not directly translate to humans. The bioavailability improvement over Epidiolex was modest. Long-term stability and real-world performance of the formulations were not assessed. Only single-dose PK was measured.

How to read the evidence

Well-characterized in vitro and in vivo work with appropriate comparator (Epidiolex), but animal data only and modest improvement in the primary outcome.

When this study was published

Published 2025.

The bigger picture

While the bioavailability improvement over Epidiolex is modest, the use of PEG-free, biodegradable emulsifiers could address growing concerns about PEG-based ingredients. This line of research points toward CBD formulations that are both more effective and potentially safer for long-term oral use.

Questions still open

Whether the PG-based SEDDS bioavailability advantage holds up in human trials
How the formulation performs with repeated dosing over weeks or months

Common questions

Why is CBD bioavailability so low?

CBD is highly fat-soluble and undergoes extensive first-pass metabolism in the liver, meaning most oral CBD is broken down before reaching the bloodstream. Even the best formulations achieve single-digit bioavailability.

Is 3.8% vs. 3.4% bioavailability a meaningful difference?

On its own, the difference is small. The more notable finding is the higher peak plasma concentrations (up to 43% higher than Epidiolex), which could translate to better therapeutic effects at the same dose.

Read the original research

Oral formulations for cannabidiol: Improved absolute oral bioavailability of biodegradable cannabidiol self-emulsifying drug delivery systems.

Colloids and surfaces. B, Biointerfaces, 255, 114879

View on PubMed ↗Publisher’s paper ↗

Citation

Sandmeier, Matthias; Wong, Ee Tsin; Nikolajsen, Gitte Nykjær; Purwanti, Asef; Lindner, Sera; Bernkop-Schnürch, Andreas; Xia, Wenhao; Hoeng, Julia; Kjær, Kathrine; Bruun, Heidi Ziegler; Jensen, Sanne Skov. (2025). Oral formulations for cannabidiol: Improved absolute oral bioavailability of biodegradable cannabidiol self-emulsifying drug delivery systems.. Colloids and surfaces. B, Biointerfaces, 255, 114879. https://doi.org/10.1016/j.colsurfb.2025.114879