IIT Hyderabad develops novel skin patch for constant drug release

Mudrika-Optimized
The amount of drug present in the patch can be increased so that the drug is at a therapeutically desirable dosage for a longer duration, say Mudrika Khandelwal (second from right) and Chandra Shekhar Sharma (left).

A novel drug-delivery system that releases drug at constant rate for extended periods has been developed by IIT Hyderabad researchers. The transdermal patch made of patterned nanofabric and loaded with a pain killer (diclofenac sodium) with half-life of just one-two hours has been made to release for 12 hours at a constant rate.

Researchers at the Indian Institute of Technology (IIT) Hyderabad have developed a novel drug-delivery system that releases a commonly used pain killer (diclofenac sodium) at the target site in a controlled fashion such that there is constant release of the drug for as long as 12 hours. The drug has low half-life of one-two hours and so constant release for up to 12 hours becomes particularly significant.

In normal circumstances, the drug gets metabolised very quickly, thereby requiring frequent dosing to maintain the desired therapeutic levels. The fluctuation of the drug plasma level is one reason why the medicine cases adverse effects.

To prevent burst or quick release of the drug, a team led by Dr. Mudrika Khandelwal from the Department of Materials Science and Metallurgical Engineering at IIT Hyderabad fabricated a transdermal patch containing the drug and made the patch highly hydrophobic (water repelling). The high hydrophobicity of the patch ensures that the highly water-soluble drug is released in a slow and sustained fashion. The results were published in the journal Applied Surface Science.

What makes the transdermal patch particularly significant is the freedom to increase the amount of drug present in the patch so that the drug is released constantly at a therapeutically desirable dosage for a longer duration.

Making of the transdermal patch

The patch was prepared by mixing the drug with cellulose acetate bio-polymer and electrospun in the form of a nanofabric. Ordinary nylon mesh with different pore sizes (50, 100 and 200 microns) was used at the site of the collector and this allowed the nanofibres to get deposited with micron-sized gaps in between.

“The non-wetting capillary action of the air pockets pushes the water away and this changes the water contact angle from about 30 degrees to 138 degrees and makes the nanofabric hydrophobic. There is higher non- wetting capillary action of the air pockets when the air gaps are smaller in size,” says Prof. Chandra Shekhar Sharma from the Department of Chemical Engineering at IIT Hyderabad and one of the authors of the paper. “Since the drug is released through a diffusion process, the increased water repelling nature (hydrophobicity) of the fabric reduces the effective area in contact resulting in reduced diffusion rate, which also reduces the drug release.”

Pore size determines drug release rate

“The drug, which is embedded in the transdermal patch, is released at a constant rate for up to 12 hours, when the pore size of the nanofabric is 50 microns. We achieved constant release for only three hours when the pore size was 100 microns. The drug without any micropatterning was released in just one hour,” says Dr. Khandelwal who is the corresponding author of the paper.

After 24 hours, the drug release profiles were the similar for fabrics with porosity of 50 and 100 microns. This is because with time, the air trapped in the air pockets is released and the hydrophobic nature is lost making the patch with different porosities to behave in a similar fashion.

“We tested transdermal release using a membrane that mimics the skin. The membrane separates the drug-loaded nanofabric from a solution that in turn mimics the body fluids,” says Dr. Khandelwal. “Different drugs can be loaded in the nanofibres to achieve constant release for a long time.”

“We embedded ciprofloxacin antibiotic in the patch and achieved similar results. The transdermal patch loaded with the pain killer [diclofenac sodium] can be used for treating local muscular pain. It may not be possible to treat deep-seated pain using this patch,” says Shivakalyani Adepu from the Department of Materials Science and Metallurgical Engineering at IIT Hyderabad and the first author of the paper.

The researchers plan to develop transdermal patch prototypes and test them on animals.

It is possible to simultaneously load two different drugs in the nanofibre and achieve even different diffusion rates for each drug as per the need. According to Prof. Sharma, it is also possible to develop nanofibres loaded with drugs for oral administration.

Published in The Hindu on November 11, 2017

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