Proteins & Peptides Liquid Formulation Development

The protein/peptide stabilization strategy is a key step in developing protein/peptide liquid formulations. As an expert in protein/peptide and formulation science, CD Formulation has the most advanced technology and industry knowledge and is committed to creating customized liquid formulation solutions for therapeutic proteins and peptides. Our team of experts uses various methods, such as adjusting pH, adding stabilizers and protective agents, and optimizing freeze-drying and reconstitution processes, to ensure that proteins/peptides maintain their original structure and function in liquid formulations.

About Proteins & Peptides Liquid Formulation

Clinically, therapeutic proteins/peptides are usually administered parenterally, which requires liquid formulations. Most liquid formulations have a simple composition, including buffer, tonicity adjuster, surfactant, and sometimes stabilizer and water. Liquid formulations of proteins/peptides usually use histidine or acetate as buffer, sucrose or trehalose as tonicity adjuster, polysorbate 20 or 80 as the surfactant, and pH 5.7 ± 0.4.

Explore Our Proteins & Peptides Liquid Formulation Development Services

A well-designed stable formulation strategy can improve bioavailability and enhance therapeutic efficacy. At CD Formulation, our experienced formulation scientists provide customized liquid formulation solutions for your protein and peptide active pharmaceutical ingredients (APIs).

The main problem in the development of liquid protein and peptide formulations is how to ensure that these active drug molecules remain stable in aqueous solution, as proteins and peptides are often damaged by chemical or physical degradation processes.

With a deep understanding of the structure, physicochemical properties, degradation pathways, and potential instability mechanisms of proteins/peptides, our scientists are good at stabilizing your proteins and peptides through the following strategies.

Protection Against Hydrolysis

• Optimize pH, which involves the use of buffers such as citrate buffer, aspartic acid buffer, phosphate buffer, acetate buffer, etc., to adjust the pH value of the protein/peptide solution to between 3–10. This is not absolute, our scientists will make reasonable adjustments to the specific pH based on the application route of your product, such as oral, injection, and ocular delivery.
• Use of Co-solvents, which involves the use of organic solvents, such as glycerol, propylene glycol, and ethanol, to reduce the dielectric constant of aqueous solutions, thereby significantly reducing the rate of protein/peptide isomerization and deamidation.
• Viscosity enhancement, which involves the use of stabilizing excipients, such as polyvinylpyrrolidone (PVP), Pluronic F68, and Poloxamer 407, to increase the viscosity of protein/peptide solutions, thereby slowing down their deamidation rate and enhancing stability.
• PEGylation, which is covalent attachment (PEGylation) of water-soluble polymers such as polyethylene glycol (PEG) to proteins/peptides to extend shelf life, and improve water solubility and stability under stress conditions.

Protection Against Oxidation

Our scientists mitigate this effect by adjusting pH, eliminating oxygen from solutions, modifying packaging to protect against light, and using antioxidants or metal chelators in formulations.

Inhibition of Aggregation, Dimerization and Precipitation

Aggregation and dimerization of proteins/peptides can occur through the formation of covalent bonds (e.g. disulfide bonds and tyrosine) or non-covalent interactions (e.g. hydrophobic forces). These aggregates can exist in soluble and insoluble forms. Our scientists stabilize protein/peptide aggregates in aqueous solutions by optimizing the pH and ionic strength of the solution, as well as using extremely soluble substances.

Hydrophobic Ion-pairing (HIP)

The technique involves the formation of an ion pair between a hydrophobic counterion and a positively charged amino acid residue (usually histidine, lysine, or arginine) in a protein/peptide. This interaction effectively shields the charged groups from the surrounding solvent, reducing their exposure to water and potential hydrolysis.

Protection Against Disulfide Exchange

Our scientists will replace the buffer system and adjust the pH value according to the characteristics of your protein/peptide to effectively protect the cleavage of disulfide bonds.

Fig. 1 Strategies that can be used individually or in combination to improve protein/peptide stability in liquid formulations. (CD Formulation)

In addition to conventional in-solution stability strategies, we have also established a unique nanoparticle platform to enhance the stability of proteins/peptides, which also serves as an excellent delivery system for protein and peptide drugs. This technology is most commonly used to develop oral protein/peptide liquid formulations. In a few cases, it is also used to develop sterile formulations for intravenous delivery of proteins/peptides.

Our Solutions for Proteins & Peptides Liquid Formulation Development

A key strategy in formulation development is the application of Quality by Design (QbD) principles and the use of statistically based screening methods. Thanks to a thorough understanding of the interaction of various stabilizing excipients in liquid protein/peptide formulations, our scientists perform careful screening of excipients and proportions by testing the effects of various stress conditions such as pH, temperature, freeze-thaw, drying, and purity, on the formulation to determine the most appropriate formulation conditions and processe.

Fig. 2 Proteins/peptides liquid formulation development. (CD Formulation)

Prototype Design and Analytical Testing

At this stage, we will conduct a comprehensive stability assessment of the protein/peptide APIs, including thermal stability, photostability, oxidative stability, etc. Based on the assessment, appropriate protective agents and cosolvents will be selected to prevent the degradation of proteins and peptides. At the same time, we will optimize the formulation pH and ionic strength to ensure that the structure and function of the active drug molecules are best protected.

Liquid Formulation Development

We will use appropriate formulation technologies such as microemulsification, gelation, and multiple emulsions to increase the solubility and stability of the drug. These technologies can improve the solubility of the drug in an aqueous solution and reduce the aggregation and precipitation of the drug, thereby improving bioavailability.

Stability Studies

We will conduct rigorous stability testing, such as accelerated stability testing, and long-term stability testing, as well as in vitro and in vivo evaluations to ensure the stability and efficacy of the formulation.

Lyophilized Formulation Conversion

If preliminary stability studies indicate that the conventional liquid formulation doesn't meet the expected product properties defined at the beginning of your project, freeze-dried product we will develop.

Process Scale-up and Technology Transfer

By managing the entire liquid formulation lifecycle in-house, we can efficiently develop an optimized platform that fits your protein/peptide formulation needs from early stage to market readiness.

Why Choose Us for Proteins & Peptides Liquid Formulation Development?

• We have extensive expertise and hundreds of successful projects in performing protein/peptide liquid formulation development.
• We have the most advanced strategies and technologies for stabilizing proteins/peptides.
• We offer comprehensive protein/peptide liquid formulation analysis and physical characterization solutions.
• We provide flexible and tailored solutions to meet our customers' specific needs and requirements.
• Fast and efficient services ensure that our customers' projects are delivered on time.

Publication

CD Formulation is always at the forefront of protein and peptide formulation development, dedicated to providing unparalleled protein/peptide liquid formulation development services to the pharmaceutical industry. Our formulation scientists use the latest protein and peptide science knowledge to create liquid formulations that optimize stability, appearance, and manufacturability. Please contact us today to get your exclusive solution if you are interested in our services.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.