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Surfactants are critical components in pharmaceutical formulations, particularly in emulsions, suspensions, and certain solid dosage forms. They reduce surface tension between different phases, aiding in the solubilization, stabilization, and dispersion of active pharmaceutical ingredients (APIs). However, the presence of trace metals can significantly impact the stability and degradation of surfactants, thereby affecting the overall stability and efficacy of the pharmaceutical product.
Trace metals such as iron (Fe), copper (Cu), and manganese (Mn) can catalyze the formation of reactive oxygen species (ROS), including hydroxyl radicals (•OH) and superoxide anions (O2•−). These ROS are highly reactive and can initiate oxidative degradation of surfactants. For example, iron ions can participate in Fenton-like reactions to generate hydroxyl radicals:
Fe2++H2O2→Fe3++⋅OH+OH−Fe2++H2O2→Fe3++⋅OH+OH−
Reactive hydroxyl radicals lead to oxidation-induced degradation of surfactants like polysorbate 80 (PS80), compromising their functionality and stability.
Trace metals can bind directly to surfactant molecules, forming complexes that alter their physical and chemical properties, such as solubility and surface activity. This binding can reduce the surfactant’s efficiency in lowering surface tension and stabilizing emulsions or suspensions.
The presence of trace metals not only affects surfactants but also has significant implications for protein stability and therapeutic efficacy in drug substances (DS) and drug products (DP):
Iron (Fe), in particular, can induce protein fragmentation through oxidative mechanisms. The generated ROS can attack protein molecules, leading to fragmentation and degradation. This can dramatically affect the stability and therapeutic efficacy of protein-based drugs.
The degradation of surfactants and fragmentation of proteins compromise the stability and integrity of pharmaceutical formulations. This can lead to reduced therapeutic efficacy and potential safety concerns, as the degraded components may exhibit altered or diminished biological activity.
Given the potential adverse effects of trace metals on surfactants and proteins, it is crucial to use excipients (inactive ingredients) of the highest purity in biologics formulations:
Pure excipients minimize the risk of trace metal-induced degradation, ensuring the long-term stability of the formulation. This is particularly important for products with extended shelf lives or those exposed to varying environmental conditions
Impurities in excipients, including trace metals, can interact with APIs, affecting the therapeutic efficacy and safety of the product. High-purity excipients help maintain the intended performance and safety profile of the drug.
Pharmaceutical products must meet stringent regulatory standards for quality and purity. Using high-purity excipients helps in meeting these standards and avoiding costly recalls or rejections due to stability issues or contamination.
Ensuring the purity of excipients leads to more consistent manufacturing outcomes and product performance. Variations in trace metal levels can result in batch-to-batch variability, affecting the reliability of the pharmaceutical product.
Pfanstiehl’s industry-leading, proprietary processes allow us to produce cell culture ingredients and cGMP parenteral excipients with exceptionally low levels of Trace Metal impurities. By reducing impurities to single-digit ppb level – 100 to 1000 times lower than traditional industry standards – Pfanstiehl’s products provide a new benchmark for purity in therapeutic biologic production.
These ultralow levels of impurities bring a host of critical advantages:
Higher Protein Yields: Lower impurities in cell culture ingredients lead to healthier cells, reduced oxidative stress, and higher yields of biologically active proteins.
Improved Consistency and Quality: The reduction of elemental impurities ensures more consistent product quality, reducing batch-to-batch variability and ensuring higher levels of regulatory compliance.
Minimized Risks in Final Formulation: By using excipients with minimal impurities, manufacturers reduce the likelihood of protein degradation, aggregation, or immunogenicity in the final drug product, improving overall therapeutic efficacy and safety.
Pfanstiehl’s Technical Sales Scientists can discuss with you to understand your challenges and provide guidance based on experience and literature reviews to reduce surfactant degradation and stabilize the structure and biologic activity of your protein therapeutic.
Let us help put together some ideas for:
in combination with other high purity excipients, Pfanstiehl high purity low metal amino acids like Pfanstiehl L-Methionine, in low concentrations, can act as chelators and sequester trace metals and thereby reducing risk for surfactant degradation.
Adjusting the buffer system’s pH and composition can enhance solubility and stability, crucial for high concentration formulations.
Pfanstiehl HPLE-LMTM TRIS Base
Pfanstiehl HPLE-LMTM Tris HCL
Pfanstiehl HPLE-LM™ Sodium Succinate Hexahydrate
Incorporating the combination of the highest purity & lowest metals excipients such as Pfanstiehl Sucrose and Pfanstiehl L-Histidine, can greatly reduce the risk of surfactant degradation.
Pfanstiehl HPLE-LMTM Sucrose
Pfanstiehl HPLE-LMTM L-Histidine
Pfanstiehl HPLE-LMTM L-Histidine HCL
For over 100 years, Pfanstiehl has made cGMP Injectable grade excipients, stabilizers, and buffer components that are guaranteed high purity, low endotoxin, and low in transition metals.
Pfanstiehl components are used in the majority of the world’s top selling biopharmaceuticals and we continue to grow every year.
Our customers know that the combination of Pfanstiehl’s award winning technical support and high purity low endotoxin low metals cGMP excipients, amino acids, and buffer salts, will help ensure better consistency from batch to batch and reduce the risk of manufacturing batch failure for your therapeutic.
If you have a protein biologic or vaccine that requires a surfactant in the final formulation, please contact us and we will be happy to discuss how we can work together to greatly reduce the risk of surfactant degradation.