The main aim of biopharmaceutical formulation is to ensure safe and stable drugs. Protein stabilization can sometimes be difficult to attain, and in such instances, advanced solutions are required.
Human serum albumin has properties which allow it to stabilize proteins in solution, preventing aggregation, oxidation and adsorption. The capacity to stabilize has its basis in some of albumin’s functions in blood, such as the carrying of small hydrophobic entities, taking part in the control of pH and osmotic pressure and playing a major role in the antioxidant abilities found in blood.
Level of Need for Advanced Formulation Solutions
Drug formulation is an essential part of the drug development process in ensuring a viable product reaches the patient. Formulation studies involve developing a preparation of the drug which is both stable and acceptable to the patient. When formulation scientists plan their formulation studies, they often have a toolbox of excipients at their disposal to help them optimize their drug formulation. Some drugs can be easily formulated using standard excipients such as sugars, detergents, amino acids or surfactants however, between 5 and 15% of all formulations have a need for advanced formulation solutions. With biopharmaceuticals becoming more and more advanced, formulation challenges get more common and the need for these advanced formulation solutions increases.
Recombinant Human Albumin: A Multi-Functional Excipient
Recombinant human albumin holds a range of natural properties rendering it the perfect stabilizer for hard-to-stabilize biopharmaceuticals. Its properties offers a range of benefits making it a multi-functional excipient and powerful tool for a formulation scientist.
Surface Adsorption Prevention – Low Dose/High Potency Drugs
Recombumin® recombinant human albumin (rAlb) prevents non-specific adsorption of a range of biopharmaceuticals. Below graph shows how Recombumin® prevents non-specific adsorption of TGF-β3 to polypropylene surfaces.
How is this achieved?
Albumin boasts special qualities which allow it to effectively shield proteins and peptides against adsorption to surfaces. These properties include:
- Numerous points of binding
- Binding powerfully to both hydrophilic (via polar groups) and hydrophobic (via nonpolar groups) surfaces
- Effectively adsorbing to surfaces and binding to clear points
Aggregation: Mechanisms and Strategies for Inhibition
It is probable that a less than ideal performance would arise from the use of non-homogenous Human Serum Albumin (HSA) preparations that can have a variety of ligands attached to the albumin together with impurities of other serum derived proteins, which can both vary depending on batch and origin of the HSA. As Recombumin® is extremely pure, its capacity for stabilization can be modulated with greater ease and consistency.
Aggregation Inhibition via Binding to Non-Native States
Case example: Determir
Production of varied kinds of aggregates:
1) Freeze Thaw (FT): Frequently results in the creation of native-like aggregates due to numerous stresses, including pH changes, higher concentration and surface denaturation (ice).
Recombinant human albumin reduces detemir particle formation in FT cycles:
Mirco Flow Imaging results pre and post 3 freeze thaw cycles using different detemir:Recombumin® ratios.
2) Shaking: Potential role of the interfacial (air-water) adsorption and denaturation of proteins with subsequent aggregation of these partly folded structures.
Recombinant human albumin reduces detemir particle formation upon shaking:
Mirco Flow Imaging results using different detemir:Recombumin® ratios.
Aggregation Inhibition via Preferential Exclusion
Case examples: Bevacizumab and Ritximab
Bevacizumab and Rituximab were produced through the purification of commercial preparations and formulated using Tween®80 and arginine, both with and without Recombumin®. Each formulation was then lyophilized and reconstituted.
Reduction in particle content after lyophilisation
Results clearly shows how the inclusion of Recombumin® reduced number of particles
Recombumin®, Enhanced Performance through reproducible characteristics
Recombumin® contains low and controlled levels of endogenous ligands that ensures consistency between batches.
Recombumin® – Formulate with Confidence
Recombumin® boasts unrivalled cGMP quality, which meets USP-NF standards as well as offering steady, guaranteed long-term supply from dependable manufacturers. Its acceptability is clearly established with leading regulatory agencies, and it is backed up through skilful technical and regulatory support.
Recombumin® is a multifunctional excipient which offers stabilization through varied mechanisms. It allows for the inhibition of aggregation across numerous stress conditions, through a variety of mechanisms and shields proteins and peptides against surface adsorption.
About Albumedix Ltd.
Too many people battle with diseases that keep them from living a full life. Healthcare professionals work hard every day to provide these people with better therapies. Together with partners, Albumedix utilize its albumin-based drug enhancing products and technologies to enable the development of more effective treatments.
With more than 30 years of experience, we are proud to be recognized as the world leader in recombinant human albumin products and technologies.
As the highest quality recombinant human albumin products ever developed, Albumedix enables the effective formulation of otherwise hard-to-stabilize drugs, cell therapies, and vaccines.
Our albumin-based technologies offer new ways of optimizing drug dosing and enhancing therapeutic performance by increasing the half-life, payload capacity, and tissue specific delivery of active pharmaceutical agents. This results in simpler treatment regimens, better performance, and, ultimately, improved patient outcomes.
Albumedix is headquartered in Nottingham, UK, with both research and large-scale manufacturing facilities. We are all committed to improving patient quality of life and are just as passionate about albumin and albumin-enabled therapies today as we were when we started 30 years ago.
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