Upgrading Health: Using Supercritical CO2 to Increase Drug Efficacy

By Shreya Kanade, GCI member-at-large

An efficient way to administer pharmaceutical drugs to a patient is through a tablet. The drugs are measured and coated in a plastic that is broken down when the drugs are injected into the person, and the drug is absorbed into the bloodstream and transported to the tissue it acts upon. The traditional processes of packaging drugs in these plastics, however, often require the usage of high temperatures and solvents that can be harmful. For example, many volatile organic compounds like benzene and chloroform are used. There is the potential for some of the solvent to remain as a residual impurity after the manufacturing process and can be toxic to the patient or the environment. These materials also need specific management to prevent them from escaping into the atmosphere. Even more, the process of coating the drugs sometimes reduces the efficiency of the dose; for instance, high temperatures and volatile solvents can cause up to a 50% drop in efficacy (1).

At the University of Nottingham, Professor Steve Howdle and his team have used green chemistry techniques to design a plastic coating that does not decrease drug efficacy. The plastic degrades in the body at a controlled rate, releasing the drug into the patient over a specific period.

Professor Howdle uses supercritical fluids (Figure 1), specifically supercritical carbon dioxide (sc-CO2), instead of the conventional benzene and chloroform solvents typically used (1). A supercritical fluid has properties of both liquids and gases at a certain pressure and at around room temperature. Using sc-CO2, conventional solvents are not required and biodegradable plastics can be used to make polymers that coat the drugs before being administered to the individual. Furthermore, it has been demonstrated that using sc-CO2 allows for the plasticization of these polymers near room temperature, which means that the drug activity is unaffected. At room temperature, the plastics are solid but when exposed to high pressure (i.e. the critical pressure of sc-CO2), they liquify and allow for the drugs to be mixed in. Once in the blood, the polymers degrade slowly over days, allowing for a steady release of the drug into the patient. This maximizes the effect of the medicine and reduces the duration of the patient’s treatment regime. Polymers can degrade at different rates and the rate of degradation can be matched with the administered drug that best suits the patient’s needs.

Figure 1. The different phases of carbon dioxide with varying temperature and pressure (2).

              These techniques can allow patients to receive medications that were previously unavailable due to the drugs being too delicate or too reactive to withstand the traditional methods of coating. Because proteins are so sensitive, they are not able to withstand elevated temperatures or strong solvents; with Dr. Howdle’s techniques, however, patients will soon have access to these treatments. Furthermore, because these processes do not include volatile organic solvents, there are no residues that could potentially be harmful to the patients or the environment.

Works Cited

Green Chemistry Principle #10: Design for Degradation

By Shira Joudan, Chair of the Education Subcommittee for the GCI

10. Design for degradation: Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.

In video #10, Matt and I discuss designing chemicals that break down once their desired function is completed. Essentially, we want chemicals to degrade to molecules that are not harmful to humans, animals or the environment.

A lot of the chemicals we use in our day-to-day lives need to be stable to perform their function. For example, if your coffee mug dissolved when you poured your coffee into it, it wouldn’t be very helpful! Similarly, if lubricants degraded under high temperature and pressure, they may not work well in the engines of our cars or planes.

Once chemicals are done providing their main function, they might end up in a landfill or wastewater treatment plant where they can enter the waters, soil and air of our environment, or be taken up by animals or humans. The biggest challenge is making chemicals that are stable during usage, but don’t persist in the environment – or in other words, chemicals that can be degraded. Another important thing – we want the breakdown products to also be non-toxic and not persistent! It’s important to remember that there are different reasons a chemical can break down. It can be due to reactions with light (photodegradation), water (hydrolysis) or biological species, often with enzymes (biodegradation).

A common example that we hear about is biodegradation, especially with the well-known “biodegradable soaps.” We can use this as a good example about how we can design soaps, or detergents, to break down more easily in the environment.

Sodium dodecylbenzenesulfonate

Figure 1 Sodium dodecylbenzenesulfonate, an example of a linear alkylbenzene sulfonate (LAS) which is biodegradable.

Sodium dodecylbenzenesulfonate (Figure 1) is a common detergent, and is often referred to as LAS, for linear alkylbenzene sulfonates. Looking at its structure, you can see that it has a linear alkyl chain with a benzylsulfonate attached to it. It is useful as a detergent because it has a polar headgroup (sulfonate) and a non-polar alkyl group, making it a surfactant.

LAS is used in many things, especially laundry detergent. It degrades quickly in the environment under aerobic conditions, or when oxygen is present, because microbes are able to use to the linear alkyl chain as energy, via a process called β-oxidation, a process which breaks down the carbon chain. Once the long chain is degraded, the rest of the molecule can be degraded as well.

Branched alkylbenzene sulfonate.

Figure 2 A branched alkylbenezene sulfonate (does not biodegrade).

If you compare LAS to a branched version (Figure 2), you can immediately see that the alkyl chain looks very different. This molecule was also used as a detergent just like the linear version, but because of the location of the branches, microbes cannot perform β-oxidation since there are no good sites for that reaction to be initiated. Therefore, these branched detergents have been phased out in most developed countries because they are too persistent – they do not biodegrade.

The main way these molecules are degraded is through microbes, when oxygen is present. So if these soaps end up directly in water, like straight into a lake, they will not be broken down very quickly (even the linear version!). This is because there are fewer microbes in water as compared to in soil. Interestingly, the branched version is 4 times less toxic than the linear version, but can cause more damage because of its persistence. This is one of the reasons that it is very important to consider persistence, or a molecule’s resistance against degradation, and not only its toxicity.

You can see how designing chemicals to break down can be very challenging, but many researchers around the world are working on this right now. Some examples are biodegradable polymers that are used in plastics, like compostable cutlery.

Principle 10 is currently one of the largest challenges in green chemistry. If scientist designing new chemicals understand more about the mechanisms that can degrade them, we may be able to make chemicals that are reliable and stable during their intended use, but break down in the environment!