Quaternary ammonium compounds (Quats/QAC) for API or excipients
Quaternary Ammonium Compounds have a long history of use in the pharmaceutical industry, where their broad antimicrobial effect against bacteria, yeast, mould and enveloped viruses makes them a reliable excipient and active pharmaceutical ingredient (API) in a range of products.
Due to their antimicrobial activities, Quats are widely used as antiseptic actives and preservatives in medicinal ophthalmic, nasal, oral and skin preparations, where they prevent bacterial infections and contamination. CTAB is also used as a detergent in downstream vaccine purification, for protein removal and precipitation.
Quats are strong surface-active compounds, characterized by a fast, long-lasting effect against common gram+ and gram- bacteria, fungi, algae and enveloped viruses such as HIV, influenza, herpes and corona. Their antimicrobial activity derives from their ability to attach to the membrane of the microorganism and disrupt it.
The Quats’ alkyl (fatty) chains have a good affinity for cellular membranes, and the mechanism of action is the disruption of intermolecular interactions. Quats can cause dissociation of the lipid layers in the microbial cellular membrane, compromising cellular permeability controls and inducing leakage of cellular contents, resulting in cytolysis.
Quats are effective at all pH levels relevant for pharmaceutical formulations, although their effectivity increases when the pH increases. The higher the pH, the lower the concentration needed to obtain an antimicrobial effect. As opposed to bacteriostatic or fungistatic compounds which only prevent micro-organisms from dividing (growing), Quats are bactericidal and fungicidal, meaning they will kill micro-organisms whether they are in a growth phase or not.
Our Quats will not affect the odour or colour of your formulation, and their ability to mix well in both aqueous and oily phases, make them an ideal antimicrobial ingredient.
Quats are also very stable and can withstand many different temperature and humidity conditions. This is supported by our full ICH Q1A stability testing and stability risk assessments. They also have a long shelf life, giving you flexibility in supply chain planning.
Our Quats have been tested against several relevant microbial strains, and shown to be effective at low concentrations. As an excipient, Quats function as preservatives. Benzalkonium Chloride (BKC) is often used in fluidic formulations such as multi-dose eye drops and nasal sprays. Such formulations are exposed to air-borne particles and human body tissue multiple times over their shelf life, raising the risk of contamination and degradation.
Just a small amount of Benzalkonium Chloride (BKC) is needed to keep ophthalmic and nasal solutions safe for patients.
BKC has been in use as an antimicrobial preservative in eye drops since the early 1940s, and remains the preservative of choice in multidose formulations. Concentrations typically vary from 0.001% to 0.2%. Its concentration would typically be 0.001%-0.005% in ophthalmic formulations and slightly higher, 0.01%-0.05% in nasal sprays. This can be much more cost-effective than addressing the issue through specially designed packaging devices, or single-use packaging.
As an API, Quats function as the key ingredient in many antiseptic formulations, including topical creams, washes, wound care products, and oral formulations used to treat throat infections, cold sores, and gum pain. Concentrations often range from 0.1% to 1%.
Benzalkonium Chloride (BKC), Cetrimide and CTAB are often found in antiseptic creams for treating nappy rash, eczema, psoriasis, acne and other dermatoses at concentrations varying from 0.1 to 1%.
Read more about antiseptic agents.
Benzalkonium Chloride (BKC) for cleansing skin, mucous membranes, and wounds at a concentration of 0.01 to 0.1%. More dilute solutions are suitable for irrigation of deep wounds.
Read more about wound care.
Benzalkonium Chloride (BKC) is also often found in gels and creams at typical concentrations of 0,01 to 0,1%, to treat herpes and cold sores infections, or as an excipient in pain relieving gum gels. Antiseptic mouth sprays with Benzalkonium Chloride (BKC) are also common.
Read more about oral and dental formulations.
Standard concentrations of Benzalkonium Chloride (BKC) in hand sanitizers varies between 0.5% and 1.5%w/w.
Read more about antiseptic agents.
Benzalkonium Chloride (BKC) is often found in solution impregnated gauzes, wipes and plasters for skin and/or wound disinfection at typical concentrations of 0.01 to 0.1%. Aqueous solutions of 0.005 to 0.02% Benzalkonium Chloride (BKC) can be used for irrigation of the bladder and urethra and 0.0025 to 0.005% solutions for retention lavage of the bladder. Surgical glues (tissue adhesive) are other examples of devices containing Benzalkonium Chloride as an auxiliary.
Read more about medical devices.
Benzalkonium Chloride (BKC) is used as an API to treat superficial infections in the mouth and throat. CTAB is used to treat throat infections at typically 1.0 mg/lozenge.
Some Quats can also be used as processing aids for bacterial and viral vaccines. In particular, CTAB is recommended by the World Health Organisation (WHO) as a purification agent in the downstream vaccine processing of polysaccharide vaccines, and is also used in the manufacture of viral vaccines, for example against influenza.
Read more about CTAB in vaccines.
Novo Nordisk Pharmatech has more than 70 years of experience manufacturing Quats such as Benzalkonium Chloride (BKC), Cetrimide, and Cetrimonium Bromide (CTAB), and 30 years’ experience in GMP manufacturing. We are part of Novo Nordisk, a Danish healthcare company and world leader in diabetes care.
If uniform high quality is the key to your products, you should begin with ours. As the world’s leading supplier of quaternary ammonium compounds (Quats), we provide only the best and safest ingredients for the pharmaceutical and personal care industries. Our ingredients are produced according to the highest cGMP standards and backed by complete regulatory documentation. This combination of high-purity products and regulatory services has made us an approved supplier to many of the world’s leading pharmaceutical companies.
We are highly specialised in pharmaceutical grade Quats. The uniform quality of our finished products – and of yours – is ensured by our efficient quality control systems, fully validated processes and rigorous laboratory quality control. In-process samples, as well as finished products, are carefully analysed in our modern, well-equipped laboratory.
Novo Nordisk Pharmatech manufactures its pharmaceutical quats in accordance with the cGMP Guide ICH Q7 for Active Pharmaceutical Ingredients (APIs), the highest available quality standard in the industry. They are inspected by the FDA and the Danish Medicine Agency (DMA).
Read more about our company here.
Chemical-based disinfection is easily achieved by alcohol contact (ethanol or isopropanol) or other classic anti-viral and anti-bacterial compounds found in many commercial products. Alcohol offers momentary disinfection by contact and evaporation, while longer lasting effects that can be provided by less volatile active compounds such as Quats (BKC), remaining on surfaces. Alcohol-based hand sanitizers (ABHS) are less user-friendly on skin than Quats-based, non-alcohol hand sanitizers (NABHS). ABHS predominate in health care settings given their low cost, however they are more worrisome due to their flammability and abuse potential.
Our CTAB can be used during the purification steps of different types of vaccines.
CTAB stands for “Cetyl Trimethyl Ammonium Bromide” and can also be called Hexadecyl trimethyl ammonium bromide or Cetrimonium Bromide. It is a powerful cationic surfactant for use in vaccine downstream purification steps. It is recommended by the WHO for the precipitation of polysaccharide-based bacterial vaccines.
CTAB is also used as a purification agent of viral antigens, whether the vaccine is egg-based, cell-based or recombinant (DNA). Whether you are manufacturing bacterial or viral vaccines, you want to minimize risks in your process by only using the purest and safest ingredients and materials.
Utilizing cGMP manufactured, pharma grade ingredients and processing aids can help you secure your vaccine production and minimize your risks. Novo Nordisk Pharmatech’s CTAB is used by many of the world’s leading vaccine producers, as we are the only manufacturer offering CTAB in cGMP pharmaceutical grade for APIs, in full compliance with ICH Q7.
Read more about CTAB for vaccine production here.
Being cGMP certified, we ensure that every aspect of our manufacturing process is in control – from our own suppliers to the finished product. From the very beginning, we source the best raw ingredients, which are sampled to check they are in specification. Throughout manufacturing, we monitor the critical parameters for each process, such as temperature or PH level, to make sure the process is in control. When each batch is finished, we perform an analysis tailored to our customers’ requirements to deliver a Certificate of Analysis. Good manufacturing practices are embedded in everything we do, as we strive to keep all our operations completely uniform.
Tightly controlled processes require not only the combined efforts of our 70-strong manufacturing team. All of our activities and all of our teams are gathered on one site here at Køge – from Research and Development, to Quality Assurance, Quality Control and even Sales and Marketing. This brings us significant advantages in terms of agility.
If you are interested in hearing more about our Quats and our company, please explore our home page or contact us for more information. We have documentation available on demand, covering the topics mentioned above.