In this interview, Prof Na Li explores the mysteries of the outcome of the particles and practical applications in real world scenarios.
Could you explain why solubility is such an important drug absorption factor?
Only dissolved drugs can be absorbed by the body. However, the poor solubility of many drugs – both on the market and in the ongoing ongoing – was a major challenge for the pharmaceutical industry.
As wording scientists, we aim to develop strategies that enhance the solubility of drugs to ensure effective absorption. Without these strategies, taking drugs for life would be different from eating a piece of brick-there would be no absorption and, consequently, no health benefit.
Is there a limit on how much can the drug break up in the solution?
Yes. While the strategies of improving solubility are strong, they do not allow infinite dissolution. Poor soluble drugs have a upper limit of concentration, which we call amorphous solubility. This is essentially the gap between the drug and the water. Even if we dissolve more medicines in the solution, any amount beyond this amorphous solubility will precipitate as a second phase, usually in the form of nanoparticles of amorphous drugs.
Did you discuss how amorphous nanoparticles are formed, but they contribute to drug absorption?
Based on the work of Dr. Sugano, we already know that forms of particles contribute to absorption. The main reason is that the unstable layer of water represents a significant obstacle to the absorption of poorly soluble drugs.
Think of drug absorption as a hiking trip – to reach our destination (absorption), we must cross the endless water layer. Even if there is a large population of molecules in bulk in bulk, only a few can of course diffuse through this barrier.
When there are small drug nanoparticles or bile miccons, they can act as vehicles, carrying large quantities of free drug during the unstable layer of water. These particles effectively eliminate the drug molecules just on the intestinal wall, allowing faster and more effective absorption. This was named as a result of drifting particles.
Credit Picture: Gorodenkoff/Shutterstock.com
Can you explain how you measured the advantages of absorption provided by these colloidal particles?
We used a two -phase diffusion setting to measure the flow and calculate the effective endless thickness of the water layer (inversely proportional to the flow). In this arrangement, we have a aqueous phase where we introduce the drug and particles and measure the appearance of the drug in the organic phase over time. To quantify the phenomenon of drifting particles, we used differential equations to draw an expression for the thickness of the unstable layer of water.
We evaluated the flow provided by amorphous drug nanoparticles and normalized the data against the flow of free drug. We analyzed our data by designing the effective permeability coefficient (which represents the absorption of drugs in the organic phase) against the solubility of the drug that synthesizes the nanoparticles. This revealed a strong linear correlation. According to the Whitney-Noyes equation, the rate of dissolution of a particle is proportional to the solubility of the drug that is the particle.
This suggests that “drifting particles The effect “is closely related to the rate of dissolution. The particles must first dissolve, release the drug on the surface of the membrane and then the free drug can be absorbed. For much slower drugs, such as soluble, dissolution, leading to a higher phenomenon.
How does the size of the particles affect the behavior of permeability of different drugs?
We created particles of different sizes to examine the effect of the size of the particles on two medicines, atazanavir and anacetrapib. For Atazanavir, we did not see any notable difference in permeability, regardless of the size of the particles.
However, for Anacetrapib, smaller particles have led to significantly faster penetration than the larger ones. This is expected, as smaller particles dissolve faster, while larger particles dissolve more slowly.
The difference we noticed in these two drugs is reduced to the mechanism of the effect of drifting particles, which includes two consecutive steps: dissolution and penetration. In the case of Anacetrapib, which is extremely insoluble, the dissolution is very slow and becomes the stage that determines the rate of the overall process. By modifying the size of the particles, we effectively coordinate the dissolution rate, which in turn affects the overall reaction rate.
Atazanavirre, which has higher solubility, is easier to dissolve. In this case, the second step-permigation-transfers the rhythm limitation factor. Even if we manipulate the size of the particles, the overall penetration rate remains unchanged because the dissolution is no longer congestion. Therefore, the size of the particles has a significant effect on anacetrapib but not on Atazanavir.
How does particle concentration affect the phenomenon of drifting particles?
We have noticed that the endless thickness of the water layer increases as the particle concentration increases. This means that although the higher concentration of particles leads to greater enhancement of permeability overall, normalized reinforcement per unit concentration is reduced. In other words, the penetration process slows down at higher particle concentrations.
To understand this, we re-examined the Whitney-Noyes equation. In addition to solubility, the bulk concentration in the unstable water layer plays a critical role. The rate of dissolution is maximized when the mass concentration is minimal, allowing effective release of the drug.
When more particles are introduced, the bulk concentration into the unstable water layer increases, leading to “non -water dissolution”. This gradual deceleration of dissolution at higher particle concentrations results in reduced permeability efficiency, which explains the trend we have observed in our data.
How do bile micelia and the phenomenon of the particles are affected?
Bile micelia, endogenous surfactants in the gastrointestinal tract (GI), play a key role in drug absorption and the effect of foods observed in poorly soluble drugs. We used sodium bullshit as a biliary system and examined its impact on the diffusion of drugs.
When we measured the endless thickness of the water layer in the presence of bile microuses, we found that for most drugs-Danazole, Efavirenz, estradiol and pelodipine-the drug associated with miccylum either had a similar or thinner unstable water layer. This suggests that biliary miccers can enhance the diffusion of the drug, sometimes even more effective than free drug.
The effect of the concentration of the Mycelia we have observed is the opposite of the drug nanoparticles. While increasing the concentration of particles has led to a thicker layer of water and slower penetration, the increase in the concentration of bile fungi reduced the endless thickness of the water layer.
This is probably due to the unique mechanism of the biliary Mycelia – they move in the unstoppable layer of water, separated to release free drug molecules and both free medicine and miccille can penetrate through the membrane. Since the miceller free is absorbed rapidly, it shifts the balance to the release of the drug to the unstable layer of water, enhancing the phenomenon of drifting particles. This explains why bile micconsies improve the absorption of the drug at higher concentrations and why the effect of food is important for poorly soluble drugs.
Pion Inc. It provides an excellent platform for exchanging cutting -edge research and promoting scientific discussions. It was my pleasure to present my work in collaboration with Pion and I appreciate their commitment to promoting pharmaceutical science through the exchange of knowledge.
About Professor Na Li 
Professor Na Li is an assistant professor in the Department of Pharmaceutical Sciences at the University of Connecticut (Uconn). She received her degree in Science and Food Engineering from the University of Technology in Southern China and Ph.D. In Food Chemistry by Purdue University, followed by postdoctoral education in an industrial and natural pharmacy in Purdue. Before joining Uconn, he worked at Crystal Pharmatech Inc., specializing in solid state chemistry and the selection of small -molecules crystals. Since its founding in 2019, her research has focused on understanding natural chemistry based on interactions between compositions and the environment in vivo.
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