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The Drug-Drug Salt: A New Way to Treat Bacterial Infections

  • Photo: Siddharth Kankaria / Research Matters

Photo: Siddharth Kankaria / Research Matters

Bacteria are the cause of some of the most deadly and widespread diseases in human civilization. Bacterial infections, with complications of drug resistance from increased antibiotic use, have increased dramatically in recent years. Escherichia coli and Staphylococcus aureus are two of the most notorious bacteria that affect several body tissues and cause a variety of diseases such as complex urinary tract infection and respiratory and skin infections. Combinations of antibacterial and antimicrobial medications are generally used to treat these infections. Most of the marketed drugs are in the form of physical mixtures with their own flaws - the two medicines are different in their chemical and physical properties resulting in different efficacies. Hence, they may not always be good as a mixture and one may be needed in more quantity than the other. 

New research by scientists at the Indian Institute of Science, Bangalore, has offered a balanced approach to tackle this problem. Prof. Gautam R. Desiraju, Dr. S. P. Gopi and Dr. S. Ganguly, at the Solid State and Structural Chemistry Unit, have designed a new multicomponent solid which is a combination of the antibacterial norfloxacin and the antimicrobial sulfathiazole in the form of a salt.

“In most of the cases, salts/cocrystals exhibit improved physicochemical properties as compared to the native drugs or their physical mixtures. The problem with a physical mixture of norfloxacin and sulfathiazole is that norfloxacin is only slightly soluble and not permeable. Making a salt/cocrystal would ensure onset of action by the two original drugs more or less at the same rate and thus can be synergistic”, explains Prof. Desiraju on the effect of combining these drugs into a salt crystal. 

Solubility and permeability are two desirable properties in a drug. The molecules must dissolve and permeate into the cells to reach the targeted area. Generally, most of the oral drugs are usually absorbed into the bloodstream in the small intestine. Once these drugs are absorbed by the blood and transported to the target areas, they try to enter those cells that need to be acted on. In the present salt from, these drugs are found to diffuse faster and together. These improved characteristics increase the ease with which antibacterials enter bacteria. Once inside, they prevent the microbes from multiplying, thus restricting their numbers. With their population kept to a minimum, the body’s immune system is able to effectively fight and eliminate them. 

However, not all antibacterials are effective against all kinds of bacteria because of the differences in the bacterial targets. If the dosage of the medications is not strong enough, they can be overpowered by the bacteria causing a recurrence of the infection and development of resistance. These enhanced properties of the salt lead to greater bioavailability – the property of being utilized by the biological system. Thus, even a smaller amount of the salt is prescribed, the amount of drug entering the bacterial cells will be more than the usual dose.

In the current alarming scenario of drug resistance, the evolution of superbugs, and forced creation of newer generation of antimicrobials and antibacterials, new and innovative methods of drug delivery are being increasingly experimented with. The formulation of a salt crystal of two commonly employed antibacterial agents (often in combination) is one such novel attempt. The fusion of these two compounds is expected to result in safer and more beneficial therapeutic treatment as indicated by all the laboratory tests. This implies a quicker and stronger attack against many bacterial infections. This new drug formulation is hoped to become available in Indian markets in the near future.

Author and research information:

Prof. G. R. Desiraju is a Professor at Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore. He may be reached at gautam.desiraju@gmail.com. Dr. Shanmukha Prasad Gopi (shanmukhaprasad111@gmail.com) is postdoctoral researcher and Dr. Somnath Ganguly has co-authored this work.

This article is based on a research paper titled "A drug-drug salt hydrate of norfloxacin and sulfathiazole: Enhancement of in vitro biological properties via improved physicochemical properties" published online in the ACS journal ‘Molecular Pharmaceuticals’.