Scientists have increased the solubility of drugs using supercritical technologies

Modern solid-formed drugs can be more efficient if their solubility increases. The international team of researches verified supercritical technology that are applied in pharmaceutic for solubility enhancement of poorly soluble drugs and revealed ways which can be used for design of preparation of nanomedicines at industrial scale. The research was published in the highly ranked journal “Nature Scientific Reports”(Q1).

In the pharmaceutical industry, approximately 70% of drugs are produced in solid form or solid suspension form. The major issue of it is low solubility: more than 60% of drugs are not soluble enough in water, and as a result high dosage must be taken to provide efficient therapeutic effects. However, high dosage of drugs will have adverse side effects for patients. For instance, non-steroidal anti-inflammatory drugs can enhance the risk of cardiovascular diseases.

Nanomedicine can be a method of solving this problem; nano size drugs have higher efficiency, and lower dosage is required to be taken, so the side effects can be minimized.

In recent research that was made by scientists from Iran, Vietnam, Ireland and Russia attention was paid to Tolmetin drug taken for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis. The researchers studied the effectiveness of supercritical technology using the example of a drug. They measured the solubility of Tolmetin in supercritical solvent and the effect of pressure and temperature of the solubility. There were used the theoretical models to simulate and predict the solubility values.

If a drug introduces a low solubility in water, it can be subjected to a micronization process to reduce its size to a value below 10 microns since particle size reduction can substantially enhance the drug bioavailability of poorly soluble substances. The solubility data vary in different processing conditions, i.e. temperature and pressure. In current research we obtained several semi-empirical correlations for Tolmetin which can be used for design of preparation of nanomedicines at industrial scale, and also to predict the performance of drug at wide range of operations.” Saeed Shirazian, a senior researcher of Computer-Aided Drug Design Laboratory (South Ural State University) says.

Image: Saeed Shirazian

Supercritical technology helps for solubility enhancement of poorly soluble drugs, so the main application of the research results would be actual for pharmaceutical industry and can help them exploit the green supercritical technology to manufacture drugs with high efficacy. Indeed, supercritical carbon dioxide is considered as green solvent, and the developed new process can be classified as green technology for preparation of nanomedicines, because no harmful organic solvent in used in preparation of the medicines.

The researchers are planning pertaining to future research to implement the relevant PAT (Process Analytical Technology has been defined for pharmaceutical manufacturing processes) tools to online control the process and the progress of drug solubility at different times. Also, the temperature and pressure need to be controlled to obtain highly reproducible data.

Daria Tsymbaliuk, photo:, archive of Saeed Shirazian
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