Design and process parameter evaluation of bilayer capsule systems for targeted ileal drug delivery

Can Bilayer Capsules Unlock More Precise Ileal Drug Delivery?

Targeting the distal small intestine, specifically the terminal ileum, remains one of the greatest challenges in oral drug delivery.

The terminal ileum is a highly relevant therapeutic target and a key absorption region for certain drugs and emerging therapeutic modalities, including biologics and nucleic acid-based therapies. Targeted delivery to this region has the potential to enhance local efficacy while minimizing systemic exposure and off-target effects.  However, achieving reliable drug release in this region remains challenging due to its dynamic physiological environment and relatively short transit time.

In this newly published study, researchers evaluated a novel bilayer capsule system designed to delay drug release beyond the proximal small intestine and support targeted delivery to the distal ileum. The system combines an HPMC- and pullulan-based inner capsule layer with an outer ethylcellulose layer incorporating sodium alginate as a pore forming agent, creating a unique approach that integrates diffusion-controlled release with environmentally responsive functionality.

The study systematically evaluated how formulation composition and manufacturing parameters influence capsule performance, including gastric resistance, permeability, disintegration, and release behavior. Specific alginate concentrations and curing conditions were identified that produced delayed-release profiles consistent with the goal of distal ileum targeting.

In this publication, you'll learn:

·         Why ileal targeting remains a significant unmet need in oral drug delivery

·         How bilayer capsule architectures can combine multiple release-control mechanisms within a single dosage form

·         The impact of sodium alginate concentration on capsule permeability and release performance

·         How curing temperature and humidity influence capsule microstructure and functionality

·         Which prototype formulations demonstrated the most promising delayed-release characteristics for distal small intestine targeting

Access the full publication to explore the findings and implications for next-generation targeted oral drug delivery systems

Reference:

1.        Millet E, Vandenbroucke SST, O’Shea JP, Griffin BT, Jannin V. Design and process parameter evaluation of bilayer capsule systems for targeted ileal drug delivery. European Journal of Pharmaceutical Sciences 2026; 224:107601. doi:10.1016/j.ejps.2026.107601.
https://www.sciencedirect.com/science/article/pii/S0928098726001752?via%3Dihub

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