Bringing Antibiotic to the Counter: What Does It Take To Produce Antibiotics?

So far, we’ve talked a lot about antibiotics. But, how did they end up at your neighborhood pharmacy? Well, read further and you’ll learn about what it takes to produce the medication that helps you feel better when you’re not well.

The antibiotic production industry is definitely a lucrative one. Maybe that explains the 10,000+ antibiotics on the market today. Despite their abundance of variety, the production of them is not the simplest. A part of antibiotic productions involves a process called fermentation. However, the processes that occur differ depending on the type of desired antibiotics. It makes sense that there are different processes for antibiotic topical ointment and swallowable tablet antibiotics.

The first step in producing antibiotics is research and testing. This part of production is long-lasting and costly. This is because it requires thousands of organisms. Sometimes, the organism found to produce antibiotic compounds has already been discovered and its back to the drawing board. If the organism being tested produces an original antibiotic compound, a lot of clinical testing and federal regulation and approval is involved.

Fermentation

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But, how do we extract this antibiotic compound from the organism on an industrial scale? This is where the fermentation process becomes essential to the production of antibiotics. In sterile conditions, the organism is grown and the antibiotic agent it produces is isolated. Some raw materials are used to create what is referred to as the fermentation broth. This broth is like a bath for the antibiotic producing organisms to grow in. It is composed of some carbon-compound such as molasses or soy meal to act as nutrition for the organism. These compounds are especially significant because they contain both lactose and glucose. Additionally, ammonia is added in order for the organism’s metabolism to run more efficiently. To regulate organism growth, water soluble salts such as zinc, iron, sulfur, copper, phosphorus and magnesium are added. However, another issue arises as the broth is made. The fermentation broth begins to foam. To counteract the foam, compounds containing silicones or lard oil are used.

The figure above puts the entire process into a visual display of fermentation that provides a more coherent idea of the production of antibiotics.

 

Post-Fermentation

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After the fermentation process, the broth is allowed to settle for three to five days, as this is when there will be a maximum amount of antibiotics. From here, the broth must be isolated and purified, whether it be through ion-exchange methods for water-soluble antibiotics or solvent extraction methods for oil-soluble antibiotics. At the end of both purification methods, the antibiotic yielded is in a purified powder that can be further refined into different products. For example, they can be made into solutions for IV bags or syringes, solid form for capsules and pills, and even a ground powder for topical ointments.

 Preparation of Antibiotics from Purified Powder

To make the IV bag or syringe, the antibiotic is dissolved into a solution so that it can be administered directly through a vein in the body. Capsules can be created by filling the bottom half of a capsule with the powdered form and closing it off with the top half of the capsule for oral administration. Finally, for ointments and topical medicine, the antibiotic powder itself is mixed with the ointment, whether it be in cream, gel, or lotion. After this final manufacturing, the melting point and pH are tested throughout shipment to ensure quality control and purity.

Neosporin and pills are common forms of antibiotics made from purified powder to create topical ointment and capsules.

Kinetic Instability of Fermented Substances

Although the fermentation process is efficient, the isolation of the antibiotic itself from the chemical solution is very inefficient because the antibiotics are extremely unstable. In fact, the half-life of thienamycin, one of the most potent natural antibiotics known to man, at a pH of 6-8 is approximately 0.3 to 6 hours, varying on the conditions applied to the solution. Additionally, olivanic acids have a chemical degradation half-life ranging from 4 to 27 hours. This kinetic instability makes it quite difficult for this process to run efficiently, but research is being conducted on making this process more efficient and useful for human consumption and the antibiotic industry as a whole.

Future of Antibiotics

So now that we’ve taken a look at how antibiotics are produced today, let’s see what can be done in the future. This really cool journal explains how synthetic biology coupled with rational engineering can help pharmaceutical engineer go beyond the status quo.

Mutagenesis is a process in which organisms’ genetic information is altered to the point where the organism is still living. This alteration results in a mutation because of its exposure to mutagens. These mutations actually work to produce antibiotics more efficiently. No wonder they there are plans to bring back.

This figure shows how the process of industrial antibiotic manufacturing has evolved over time.

Still interested? Of course you are. For some more information on the processes of antibiotic manufacturing check out the following links:

The Synthesis of Antibiotics

Industrial Antibiotic Production (download)

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