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A New Way to Improve Sustained-release Drugs is Here

2020-12-08
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When taking sustained-release drugs, the drugs will slowly be released into the blood and provide help within a certain period of time. Tragedy can occur when the drug dissolves too slowly or too quickly. For example, OxyContin, which contains Oxycodone (the opioid family), normally provides 12 hours of pain relief, but in some patients it dissolves faster, causing patients to take it more frequently, and ultimately lead to addiction.
However, assessing how drugs dissolve in the body is surprisingly tricky. Drug solubility must be measured under laboratory conditions, which should be as close as possible to mimic what happens in the body. In a recent paper published in Scientific Reports, researchers at the University of California, Riverside described a simple and inexpensive method to measure drug dissolution, which will help pharmaceutical companies develop better drug release products .

A new way to improve sustained-release drugs
A new way to improve sustained-release drugs is here, and it’s really easy this time!

Many factors can affect the dissolution of drugs in the body, including the pH value and chemical composition of gastrointestinal fluid, fluid dynamics caused by gastrointestinal contraction, the patient’s gender and metabolism, etc. For example, the manufacturer of OxyContin pointed out that taking the drug after a high-fat meal can increase the level of oxycodone in the patient’s blood by 25%.
Pharmaceutical companies usually test the drug by placing the drug in a container that simulates the gastrointestinal tract or the contents of the gastrointestinal tract, and then stirs the fluid to reconstruct the gastrointestinal dynamics. Regularly take a small amount of liquid samples, and use UV-visible spectroscopy or high performance liquid chromatography to measure the drug concentration that increases over time. The data from this test is used to construct a model of the expected behavior of the drug in the body.
Common test methods all have disadvantages. For example, a small difference in the placement of a tablet container can double the measured dissolution rate. You may also encounter equipment clogging, flow obstruction, and air bubbles, all of which affect the way the drug is dissolved. In addition, the measurement process is time consuming, laborious, usually non-repeatable, and involves expensive equipment. Existing methods only provide “snapshots” of dissolution taken at sampling points to provide limited information.

Professor William Grover
(Image source: Professor William Grover, the main leader of this research)

The study took a completely different approach. The researchers decided to measure the decrease in mass of solid particles as they dissolve, rather than the increase in drug concentration in the liquid. The team uses a glass tube that is bent like a tuning fork to maintain its resonance frequency vibrating through an electrical circuit, which is determined by the mass of the tube and its contents.
A brief change in frequency was observed when the test tube was filled with simulated stomach and intestinal contents, and over-the-counter drug delivery particles were passed through the test tube. When drawing, compare the peak of the resonance frequency with time to understand the buoyancy of the drug particles at this time. When the particles travel back and forth in the vibrating tube during dissolution, their weight during the entire dissolution process can be monitored and the dissolution curve of a single particle can be obtained.
The researchers said that the technology solves many shortcomings of the existing test methods, does not require additional analytical equipment, and is suitable for fast-dissolving and slow-dissolving formulas; the dissolution difference between individual particles in the drug can be easily seen; By providing the dissolution profile of a single particle, this method can capture changes in the dissolution behavior of particles that other methods cannot achieve; compared with traditional methods, this technique is cheaper and easier to implement.
Researchers expressed the hope that these data can increase existing dissolution methods and help drug developers and manufacturers to make better controlled-release drugs. Medicilon has a technology platform for high-end formulations such as sustained and controlled release drug delivery, and has rich R&D experience in the development of sustained and controlled release formulations. Medicilon will continue to pay attention to the progress of this research, hoping to help the development of sustained and controlled release drugs.

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