Original title: Hydrodynamically decoupled nanoprecipitation (HDNP): A multi-stage strategy for supersaturation, controlled delayed nucleation, and stabilization of low LogP poorly-water soluble drugs
Luis Castillo-Henríquez, Clélia Mathieu, Rabah Gahoual, Dhanang Edy Pratama +4 · August 2026
Many modern medicines do not dissolve well in water, which makes them hard for the human body to absorb. Older methods create tiny drug particles by rapid mixing, but they only work for highly oily drugs. Researchers developed Hydrodynamically Decoupled Nanoprecipitation, or HDNP, to handle less oily drugs. The process works by separating three critical stages: making the solution highly concentrated, starting particle formation, and coating the particles so they do not clump. By pulsing liquid through special flow conditions, researchers controlled when and where particles form. They tested this on the drug dexamethasone. HDNP successfully created stable, mostly non-crystalline nanoparticles. These tiny particles dissolved better than the standard powdered drug and stayed stable for at least two weeks. The team also tested another drug, prednisolone, showing this platform can help process other poorly water-soluble medicines with low oil solubility.
Imagine trying to make snow in a jar by mixing water vapor and cold air. If you mix them too fast, you get a fog of tiny droplets that quickly melt. If you mix them too slowly, no snow forms at all. The trick is to control the mixing so that the vapor first becomes supersaturated, then slowly forms snowflakes, and finally stabilizes them. In this paper, the researchers control the flow of the drug solution and water in a similar way, using a special pulsating flow to separate the steps of making the solution supersaturated, forming particles, and stabilizing them.
Many potential drugs fail because they dissolve too slowly in the body. This method turns such drugs into stable nanoparticles that dissolve faster and more reliably. It could make more medicines effective, especially for drugs that were previously too water-friendly for existing nanoparticle techniques.
The method has only been demonstrated on two corticosteroid drugs. Long-term stability beyond two weeks was not reported. The approach may need adjustment for other drug compounds. In vivo performance and scalability are not addressed.
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Hydrodynamically decoupled nanoprecipitation (HDNP): A multi-stage strategy for supersaturation, controlled delayed nucleation, and stabilization of low LogP poorly-water soluble drugs — Luis Castillo-Henríquez, Clélia Mathieu, Rabah Gahoual et al. — International journal of pharmaceutics: X — doi:10.1016/j.ijpx.2026.100656
Abstract licence: CC BY
Explanation generated by Synthesis from the abstract — it is not the original paper.