With many classes of antimicrobial agents on the market, it can be difficult to choose the right one for a new formulation. From alcohols to quaternary ammonium compounds, each type of agent has a unique mode of action, with varying degrees of efficacy.
Antimicrobial agents can be used both as active pharmaceutical ingredient (API) and as excipients. As an API, they are commonly seen in antiseptic creams for skin conditions like eczema and psoriasis or in antiseptic solutions, and in oral products for treating throat infections, gum pain, and cold sores.
When choosing an antimicrobial API, it is very likely that local regulations will demand a cGMP ingredient. In addition, several pieces of documentation will be required to support the API qualification, e.g. pharmacopeial compliance. Full compliance to both monographs and general notices and chapters is recommended.
When used as an excipient, on the other hand, antimicrobial agents help to preserve formulations. It is important that preservatives do not compromise the quality or performance of a formulation or product but simply protect it against microbial proliferation throughout the entirety of the product’s manufacture, shelf life, and usage. According to the American Pharmaceutical Review, the most effective preservatives offer a wide spectrum of antimicrobial activity, ideally at low inclusion levels.
The selection process for an antimicrobial agent intended for use as an excipient should not differ too far from the guidelines for antimicrobial API selection. The main difference is that, when it comes to excipients, not all countries will require cGMP guidelines to be followed. However, based on a risk assessment of the product, it remains preferable to source a cGMP ingredient where available. Aside from this important point, most manufacturers will look for an ingredient that is simple, robust, and cost effective.
There are many other aspects to take into consideration. On a recent webinar about antimicrobial ingredients and their selection, Chantale Julien, product manager for quaternary ammonium compounds at Novo Nordisk Pharmatech, explains: “If we look first of all at the ingredient itself, of course you want it to be efficacious. You will have to evaluate if you are looking for a broad spectrum antimicrobial, or if you want to focus on specific microorganisms, for use as an API, for example.”
Other important points to consider include safety and quality. It is also essential to evaluate the reliability of the company supplying the ingredient: do they provide sufficient communication and documentation? Will they ensure you are notified about any change to the product?
Finally, concerning the finished drug product, the route of administration and type of delivery system can also affect the decision.
Is Benzalkonium Chloride a good choice?
One antimicrobial agent that pharmaceutical companies have turned to time and time again is Benzalkonium Chloride (BKC) – a well-known quaternary ammonium compound that has supported pharmaceutical formulations as far back as the 1940s.
As a cationic (positively charged) surfactant, the Benzalkonium Chloride molecule attaches itself strongly to negatively charged microbial membranes. Its ability to then permeate and destabilise the structure of the membrane is the main mechanism behind BKC’s ability to deactivate microbial organisms and enveloped viruses.
“Its antimicrobial effect is very well documented in several scientific papers,” says Julien. “It is a very stable molecule; it is very resistant to several temperature and humidity conditions.”
Another reason Benzalkonium Chloride could be a suitable choice is its ability to work across a wide pH range, including levels as low as 4 and high as 11. It has proved to be most effective at high pH.
Later in the webinar, she also shares the results of a recent study investigating the efficacy of BKC against gram positive and gram negative bacteria and yeast. There are many other reasons to consider Benzalkonium Chloride. To learn more about how to choose an appropriate antimicrobial agent for a new pharmaceutical product and whether Benzalkonium Chloride could be a good choice for your next formulation, download the short webinar below.
