Solving the drug solubility problem with silica nanoparticles

Researchers at Harvard University and Hong Kong China University have developed methods that increase the solubility of drug molecules up to three orders of magnitude. This could be a breakthrough in drug formulations and delivery.

Over 60% of drug candidates suffer from poor water solubility, limiting bioavailability and treatment survival. Traditional techniques such as particle size reduction, solid dispersion, lipid-based systems, and mesoporous confinement often have drug-specific limitations, are expensive to implement, and are prone to stability issues.

The newly developed approach addresses these issues by exploiting competitive adsorption mechanisms of drug molecules and water on the designed silica surface. It is possible to avoid chemical modification of the drug molecule or to achieve solubility using additional lytic agents, replacing multiple drug delivery techniques.

In “Improved drug solubility through competitive adsorption on silica nanosurfaces with ultra-higher silanol density,” published in the minutes of the National Academy of Sciences, researchers explained the nanosurfaces adsorbed in dry states, and once introduced into water. This article explains nanosurfaces.

Silica nanoparticles ranging from 7 to 22 nm were used as raw materials. These nanoparticles were characterized by high urinary band convex surfaces and formed a porous template that could aggregate through controlled evaporation to adsorb drug molecules. Competitive adsorption between water and drug molecules on these engineered surfaces promotes drug dissolution by two to three orders of magnitude.

The US Food and Drug Administration classifies silica that are generally recognized as safe. The silanol density on traditional silica surfaces is 4-6 OH/nm², insufficient for strong interactions with drug molecules or water.

The researchers increased this density to a maximum of 20 OH/nm² to create a hyperaffinity surface. This strengthening allows the surface to adsorb drug molecules anhydrously, and when exposed to water, the water molecule undergoes a competitive adsorption process in which the water molecules replace the drug molecules, enhancing rapid desorption and dissolution.

Ibuprofen was used as a model drug for in vitro and in vivo testing. Dissolution studies showed that 90% of the drug was released within 1 hour, compared to less than 20% from crystalline ibuprofen over 6 hours.

In vivo studies using mice showed almost twice the peak plasma concentration and 1.5 times the drug exposure compared to commercially available products.

The team also tested the formulation methods of 15 soluble active pharmaceutical ingredients, including ketoprofen, docetaxel and fenofibrate. For all test drugs, solubility increased from 10 to 2,000 times compared to the crystalline form.

A two-year stability test showed no significant degradation in solubility performance.

Computational analysis using the sensory theory of density supports experimental observations and shows that water molecules favorably replace adsorbing agents due to the high binding affinity of the highly populated silanol surface.

Researchers believe they have found a solution to the solubility problem of drug delivery that is cost-effective and scalable for mass production, yet applicable to a wide range of drugs. When research results are converted into real-world results in clinical research, it can have a significant impact on drug development, manufacturing costs, amounts required, and drug availability.

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