Solubilization behavior of diclofenac sodium in polyethylene glycol 400/water mixtures: A solubility and thermodynamic study

Many medicines are designed to fight illness, but they face a simple physical hurdle before they can work: they must dissolve in the body's fluids. If a drug cannot dissolve easily, it cannot be absorbed into the bloodstream, and the patient receives little to no benefit. This is a common challenge for a widely used painkiller and anti-inflammatory drug called diclofenac sodium. While the drug is effective at reducing pain and fever, it does not mix well with water, which is the primary liquid in our bodies. To get around this, scientists often mix water with other liquids that can hold the drug more easily, a technique known as cosolvency. The goal is to find the perfect blend of water and another liquid that allows the maximum amount of medicine to dissolve, ensuring the drug can be delivered effectively.

In a recent study, researchers set out to explore a specific liquid mixture to see how well it could dissolve diclofenac sodium. They focused on combining water with polyethylene glycol 400, a clear, thick liquid often used in pharmaceuticals. The team, based at Tabriz University of Medical Sciences in Iran, wanted to understand exactly how much of the drug could dissolve in this mixture at different temperatures. They also aimed to map out the energy changes that happen when the drug dissolves, looking at whether the process absorbs heat or releases it, and whether the disorder of the molecules increases or decreases. By measuring these factors, they hoped to create reliable mathematical tools that could predict how the drug behaves in this environment without needing to run new experiments every time.

The researchers began by preparing small tubes containing different ratios of water and polyethylene glycol 400. They added more of the drug than could possibly dissolve, creating a saturated mixture where solid drug particles sat at the bottom. These tubes were shaken for three days in a temperature-controlled environment to ensure the drug and liquid reached a perfect balance. The team tested the mixtures at four specific temperatures, ranging from a cool 298.2 Kelvin to a warmer 313.2 Kelvin. After the shaking stopped, they separated the clear liquid from the solid particles and measured how much drug was dissolved using a light-based instrument. They repeated this process three times for each mixture to ensure their numbers were accurate.

The results revealed a clear pattern. In pure water, the drug had the hardest time dissolving. As the researchers added more of the polyethylene glycol 400, the amount of drug that could dissolve increased steadily. The highest solubility was found when the mixture contained 60% polyethylene glycol 400 by weight. At this specific ratio, the liquid held the most drug, and this capacity grew even larger as the temperature rose. The team observed that the drug dissolved best when the liquid environment could interact with both the water-loving parts and the oil-loving parts of the drug molecule. The mixture of water and polyethylene glycol 400 seemed to provide just the right balance to surround the drug molecules and keep them in solution.

To make sense of these findings, the scientists tested several mathematical models to see if they could predict the solubility data they had collected. They used equations that relate solubility to temperature and the composition of the liquid mixture. The models performed well, with the most accurate ones predicting the experimental results with very small errors. One model, which combined temperature and liquid composition, proved particularly useful for estimating solubility across the entire range of conditions they tested. This means that in the future, scientists could use these equations to estimate how much drug would dissolve in this mixture without having to measure it physically every single time.

The study also looked at the thermodynamics, or the energy story, behind the dissolving process. The researchers calculated the energy changes involved and found that the process required heat, meaning it was endothermic. In simpler terms, the drug absorbed energy from its surroundings to break apart and mix with the liquid. Despite positive ΔG° values suggesting the process is non-spontaneous at saturation, the substantial positive entropy values revealed a significant entropy-driven contribution. However, the data ultimately showed that the dissolution of diclofenac sodium in these specific mixtures was primarily an enthalpy-driven process. This balance of energy and disorder made the dissolution favorable in these specific mixtures.

Ultimately, this work provides a detailed map of how diclofenac sodium behaves when mixed with water and polyethylene glycol 400. The researchers confirmed that this mixture is highly effective at dissolving the drug, especially at higher temperatures and when the polyethylene glycol 400 makes up about 60% of the blend. By validating mathematical models against their experimental data, they have created tools that can help formulate better medicines. The findings suggest that this specific liquid combination could be a valuable option for improving how this painkiller is prepared and delivered, ensuring that more of the active drug reaches the body where it is needed.