Lyophilized Formulation Development

BOC Sciences specializes in providing best-in-class lyophilized (freeze-drying) formulation development services to meet the specific needs of the industry.

What is lyophilization?

Drug lyophilization refers to the process of stable substance drying, in which the drug solution crystallizes, forms relevant structures, and then, through further analysis, reduces the amount of the solution to the point where it cannot sustain biological growth or chemical reactions. The freeze-drying process for drugs can retain the original physical and chemical properties, physiological activities, and reduce the loss of active ingredients of drugs, and lyophilized formulation usually have a porous and loose structure, which can make drugs quickly recover their activity and water. The freeze-drying preparation contains a low amount of water, which is conducive to long-term preservation, so the drug freeze-drying process is an effective method of drug drying. The following conditions need to be met during the use of drug freeze-drying: First, the temperature of the drug curing should be within the allowable range of the equipment; Second, the drug disintegration temperature also needs to be within the allowable range of the equipment; Third, the crystallinity of water should be higher than 0.5.

Our lyophilized formulation development service

Lyophilized formulation development

Excipients screening: expanding agent, freeze-protective agent, freeze-drying protective agent, stabilizer selection, to ensure the stability of the preparation in the freeze-drying process.

Buffer selection and optimization: Buffer systems are customized to maintain the pH and stability of a protein or peptide drug.

Lyophilization process optimization

• Drug preparation process

Drug preparation is the key to the pharmaceutical process, taking into account the biological activity of the liquid, the co-solution point and the solid-liquid ratio to ensure efficacy and reduce interference. The selection of the liquid preparation process must be combined with the chemical stability of the compound (such as temperature sensitivity, pH sensitivity, etc.) information to design, not for the purpose of examining the sequence of transitional studies. The reason for the study of this process is that the liquid dispensing process and the liquid-solid transformation process need to be carried out in a considerable time or have an impact on the relevant substances, which are indicators of product safety.

• Liquid medicine pre-freezing process

Pre-freezing is the core of drug freeze-drying technology, which aims to solidify the free water and bound water in the drug solution to ensure the structural integrity, stability and long-lasting activity of the drug. Pre-freezing failure will lead to different sizes and shapes of ice crystals, affect subsequent sublimation and analytical drying, and ultimately affect the quality of drugs. The pre-freezing technology includes global supercooled crystallization and directional crystallization, where the directional crystallization is faster but the operation requirements are higher.

• Sublimation drying

Sublimation drying is to remove the free water formed in the pre-freezing process. It is necessary to start the vacuum pump in the freeze-drying box to provide the appropriate vacuum degree and temperature to sublimate the ice crystal of the drug material. The vacuum degree is too high or too low will affect the sublimation efficiency, which should be controlled at 10~30 Pa, the heating plate temperature is controlled between -10 ℃ and 10 ℃, and the temperature of the water refill is lower than -4 ℃.

• Desorption drying

Desorption drying is used to remove residual moisture after sublimation, including structural water and physicochemical combined water. It is necessary to increase the temperature of the heating plate and control the vacuum degree of the box, so that it is maintained at 2~3 pa until the analysis is completed.

• Sealed storage

After the freeze-drying is completed, the plug parting operation is carried out. This process also needs to determine whether the negative pressure environment or inert environment is required in the container according to the product characteristics.

Analysis and characterization services

Physical characteristics: Assess the appearance (e.g., cake structure, color), reconstitution time, and completeness.

Titer and purity testing: Titer analysis, high performance liquid chromatography, UV-VIS spectrophotometry and other relevant analyses to ensure product integrity.

Residual moisture analysis: Techniques such as Karl Fischer titration are used to measure the moisture content in the final product.

Accelerated stability testing: Perform accelerated stability studies to predict long-term stability.

Real-time stability testing: Long-term stability studies are conducted according to ICH guidelines to verify the shelf life of the product.

Scale-up and lyophilization technology transfer

Pilot scale production: Establish and optimize the pilot scale freeze-drying process based on the results of the laboratory scale.

Technology transfer: Seamlessly transfer expanded processes to commercial production facilities, ensuring consistency and compliance.

Advanced technology and equipment

• Freeze dryer
• Differential scanning calorimetry (DSC)
• Freeze-drying microscope (FDM)
• Karl Fischer titration
• Near infrared spectroscopy (NIRS)
• Analytical balance and automatic pipetting system
• High performance liquid chromatography
• Particle size analyzer

Our service advantage

Innovation: Our R&D team continues to explore the boundaries of freeze-drying technology, combining the latest scientific research results to provide customers with cutting-edge solutions.

Flexibility: Whether it is a small molecule drug or a large molecule biologics, we can provide tailor-made services to meet the diverse needs of our customers.

Fast response: Efficient internal processes and strong research and development strength ensure timely delivery of projects and help customers seize market opportunities.

Quality assurance: Strictly follow GMP and GLP specifications to ensure that each preparation meets international standards to ensure patient safety.

Full support: From concept design to commercial production, we provide one-stop services, includingpre-formulation studies, formulation development and regulatory support, to accompany customers every step of growth.

FAQ

1. Why is lyophilization important in pharmaceuticals?

Lyophilization is crucial in pharmaceuticals because it stabilizes drugs, biologics, and other sensitive products by removing water without exposing them to high temperatures. This helps in maintaining the product's potency, efficacy, and shelf life.

2. What services does your company offer for lyophilized formulation development?

• Pre-formulation studies
• Formulation development
• Cycle development and optimization
• Scale-up and technology transfer
• Analytical method development and validation
• Regulatory support

3. How do you optimize the lyophilization cycle?

• Determining the optimal freezing conditions
• Optimizing primary and secondary drying phases
• Conducting thermal analysis to identify critical temperatures and parameters

4. What technologies and equipment do you use for lyophilized formulation development?

• Laboratory-scale, pilot-scale, and GMP-compliant production lyophilizers
• Differential scanning calorimetry
• Karl Fischer titration
• Freeze-drying microscopy
• Stability chambers

5. How do you ensure the scalability of the formulation?

• Developing pilot-scale batches to validate the formulation and process
• Scaling up to GMP production levels
• Providing technology transfer support to commercial manufacturing sites

6. What analytical methods do you develop and validate?

• Quantifying APIs and excipients (assay development)
• Conducting stability studies
• Measuring residual moisture content

7. Can you handle both small and large-scale projects?

Yes, we can handle projects of various scales, from initial laboratory-scale development to pilot-scale production and full GMP-scale manufacturing.

8. What information do I need to provide to start a project?

To start a project, provide us with details about your product, including the API, desired excipients, intended use, and any specific requirements or challenges you anticipate. This information will help us tailor our services to meet your specific needs.