Pfanstiehl Solutions to Reduce Surfactant Degradation in Biologic Formulations

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.

Mechanisms of Surfactant Degradation Induced by Trace Metals

Catalytic Degradation by Reactive Oxygen Species:

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.

Metal-Surfactant Complex Formation:

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.

Impact of Trace Metals on Protein Stability and Therapeutic Efficacy

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):

Protein Fragmentation:

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.

Reduced Therapeutic Efficacy:

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.

Importance of Using the Purest Excipients

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:

Stability of Formulation:

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

Efficacy and Safety:

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.

Regulatory Compliance:

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.

Consistent Performance:

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.

What Can Pfanstiehl do to Help?

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:

Utilizing Metal Chelators:

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.

Pfanstiehl HPLE-LM^TM L-Methionine

Optimizing Buffer Systems:

Adjusting the buffer system’s pH and composition can enhance solubility and stability, crucial for high concentration formulations.

Pfanstiehl HPLE-LM^TM TRIS Base
Pfanstiehl HPLE-LM^TM Tris HCL
Pfanstiehl HPLE-LM^TM Sodium Gluconate

Utilizing Highest Purity Excipients and Stabilizing Agents:

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-LM^TM Sucrose
Pfanstiehl HPLE-LM^TM L-Histidine
Pfanstiehl HPLE-LM^TM 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.

Delivering on the Promise of Purity

Delivering on the Promise of Purity^TM