Impurities in drug formulations can of course affect efficacy and are a key element which needs to be addressed during manufacture. Avantor offers products to help manafacturers meet these challenges
Pharmaceutical manufacturers have always been concerned with impurities in drug formulations. The reason is simple: Impurities in pharmaceutical and biopharmaceutical manufacturing materials can reduce the efficacy of active pharmaceutical ingredients (APIs). This is an issue of even greater concern to pharmaceutical manufacturers when they develop and work with new APIs that, while making better treatment options possible, are increasingly prone to stability issues and more sensitive to impurities.
Avantor Performance Materials provides high-purity products to help manufacturers meet the challenges of manufacturing complexity and lack of tolerance for impurities in formulations. Over the years, we’ve brought to market products that are consistent, more advanced and higher in purity – from solvents to sugars, buffering salts, chromatographic media, to denaturants and surfactants.
Among the products we’ve offered to the pharmaceutical industry are several types of polysorbate excipients. These materials often are used by formulators in parenteral dosage applications. They also can be used in solid and liquid dosage form pharmaceutical and biopharmaceutical products.
Composed of fatty acid esters of polyoxyethylene sorbitan, polysorbates are surfactants which are amphiphilic and non-ionic. The surface activity of polysorbates serves to prevent surface adsorption and to stabilise proteins, by reducing the alteration or aggregation of proteins during manufacturing, distribution and storage. The largest fatty acid component dictates the general type of polysorbate— for example, polysorbate 20 is based on lauric acid - a saturated straight chain hydrocarbon - while polysorbate 80 is based on oleic acid - an unsaturated double bond- containing hydrocarbon. These structures provide appropriate hydrophilic-lipophilic balance (HLB) numbers and low critical micelle concentration (CMC) values, the factors responsible for their common use in drug formulations. Since surface active impurities can impact the CMC values, it is critical to control such impurities to maintain effectiveness of polysorbates.
When formulated with poorly soluble drugs, polysorbates provide improvements in solubilisation, and emulsions with polysorbates are widely recognised among formulators for enhanced stability and improved shelf life of the formulation. (The choice between polysorbate types depends on their specific interaction with APIs or other excipients.)
Avantor’s JT Baker brand Polysorbate 20 and Polysorbate 80 products have been used to address stability and API effectiveness issues for several years. Formulators of biopharmaceuticals are becoming increasingly concerned with further reducing levels of endotoxins, peroxides and other impurities in excipient materials. In response to these concerns, we have introduced new versions of these polysorbate products which offer higher purity levels.
The Super Refined versions of Polysorbate 20 and Polysorbate 80 are created via a proprietary flash chromatographic process. The process serves to reduce polar and oxidative impurities (such as peroxides and aldehydes) down to levels not previously achieved with traditionally produced polysorbates. The decreased level of impurities helps maintain API integrity and stability in formulations like parenteral drugs involving monoclonal antibodies or recombinant proteins (such as certain cancer drugs), and other formulations in suspension or emulsion dosage form.
As manufacturers look more closely at the issue of impurities in their formulations, they are demanding that suppliers match their own emphasis on purity and quality of materials through rigorous quality assurance. Customers increasingly are choosing suppliers that can offer features such as cGMP manufacturing and subdivision capabilities, FDA-inspected and ISO-certified facilities, and rigorous multi-compendial requirements.
Increasingly, customers are looking to work with companies that see themselves more as partners than suppliers. We make it possible for customers to match the right level of purity to their specific API needs. It’s an example of the type of collaboration between manufacturers and suppliers that will be needed to develop the excipient technologies necessary to support more effective