Proteins & Peptides Buffer-free Lyophilized Formulation Development

Long reconstitution times for lyophilized high-concentration protein/peptide drug products can limit the practical usability of the product. As experts in protein/peptide formulation science, CD Formulation has been committed to exploring the development of buffer-free lyophilized protein/peptide formulation for decades, which have short reconstitution times, allowing the elimination of some analytical characterization studies and simplifying others. We use the most advanced buffer-free technology to effectively improve the solubility and reconstitution speed of proteins/peptides by precisely controlling the pH, temperature, and processing conditions of the formulation.

Potential Advantages of Proteins/peptides Buffer-free Lyophilized Formulations

Reconstitution time for protein and peptide lyophilized products can severely compromise the potency or usability of the lyophilized product due to the presence of buffer. Buffer-free lyophilized formulations offer a number of potential advantages over conventional lyophilized formulations:

• Using a buffer-free formulation eliminates the unknown variables of residual buffer capacity and protein stability due to the attachment of buffer salts to the antibody.
• Toxicology and regulatory issues caused by the presence of buffers are avoided.
• Degradation of some buffer excipients themselves, such as arginine or histidine, is avoided.
• Some buffer solutions, especially those containing phosphates or arginine, do not maintain pH during freezing. Phosphate buffers, in particular, selectively precipitate during freezing, increasing the acidity from pH 7 to pH 3.
• Other buffers, such as acetate, may sublime during primary drying. These issues do not occur with buffer-free lyophilized products.
• Buffers such as citrate and succinate lower the freezing point of the solution.
• Excipients such as citrate and phosphate, alone or in combination, may impede endotoxin recovery from drug products, masking the true level of residual endotoxin.
• As charged species, buffer salts interact with antibodies during membrane operations, affecting ultrafiltration/diafiltration (UF/DF) and similar fill and finish operations.

Explore Our Proteins & Peptides Buffer-free Lyophilized Formulation Development Services

Since protein solutions are inherently self-buffered and the buffering capacity of the system varies with protein concentration, our senior formulation scientists will develop buffer-free lyophilized formulations by exploring the stability of your therapeutic protein/peptide at different concentrations in order to design and screen the best formulation strategy.

During the entire design strategy development and screening process, stability and reconstitution time were selected as the most important factors. This is because the stability of the protein is critical to its activity and efficacy, while the reconstitution time directly affects the ease of use and patient compliance with the drug.

Our key studies of your buffer-free lyophilized formulation development program may include:

Lyophilized Formulation Development

Design and develop buffer-free and conventional buffered protein/peptide lyophilized formulations for stability studies, ranging from 20 to 160 mg/mL. Our scientists evaluate different concentrations, buffering schemes, pH values, and lyoprotectant additives to screen for the optimal formulation.

Buffering schemes that can be designed include:

• Fully formulated lyophilized formulations, formulations with conventional buffers and lyoprotectants.
• Buffer-free lyophilized formulations, formulations with only lyoprotectants.
• Excipient-free lyophilized formulations, formulations with neither buffers nor stabilizers added.

Stability Studies

Evaluate the feasibility of the lyophilized formulation without buffering components, monitoring factors include pH stability, protein integrity, and protein aggregation. Protein stability is assessed by visual inspection, subvisible particle analysis, protein monomer content, charge variant analysis, and hydrophobic interaction chromatography.

Our Expertise

CD Formulation has the most advanced knowledge and technology in formulation development to provide comprehensive support for your high-concentration lyophilized formulation development, including:

Process Analysis and Physicochemical Characterization of Lyophilizates

The development of a lyophilized protein/peptide drug product formulation should go hand in hand with the corresponding freeze-drying process. Our scientists thoroughly evaluate the quality of the drug product and the success of the freeze-drying process based on your expectations.

We use a wide range of process analytical tools (PAT), taking in-process samples and analyzing them using a suite of physicochemical characterization methods appropriate for lyophilizates. Using this precise procedure not only ensures the robustness of the freeze-drying process and is able to produce the highest quality lyophilized drug product, but also saves time overall.

Fig. 1 Freeze-drying process flow chart. (CD Formulation)

Freeze Drying Process Cycle Design and Optimization

Suitable shelf life, good cake appearance, and economical freeze-drying process are the main goals in developing lyophilized (bio)pharmaceutical products. Our scientists use a science-based approach to design and optimize freeze-drying cycles. The approach is based on the knowledge of critical product temperatures including collapse temperature (Tc) and glass transition temperature (Tg´) of the maximum freeze concentrated solution. Based on these temperatures, appropriate process parameters are selected to achieve a robust process, stable product, and economical run time.

Robustness Testing, Scale-up, and Transfer

Transferring a lyophilization cycle from CD Formulation to the manufacturing site is a critical step in the development process. We are committed to designing and developing robust and scalable lyophilization cycles that allow for smooth and efficient process transfer.

Why Choose Us for Buffer-Free Lyophilized Formulation Development Services?

• We have extensive expertise and hundreds of successful project experiences in executing protein/peptide liquid buffer-free lyophilized formulation development.
• We are equipped with state-of-the-art facilities and technologies, capable of processing a wide range of proteins and peptides, such as monoclonal antibodies, recombinant proteins, ADCs, etc.
• We provide seamless support from formulation research to market.
• 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 buffer-free lyophilized formulation services to the pharmaceutical industry. Our formulation scientists combine proven lyophilization technology with the latest protein and peptide science knowledge to create buffer-free lyophilized 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.