Lyophilization Stability Enhancement
In the pharmaceutical industry, operators use lyophilization to remove water from drug formulations, thereby increasing the stability and shelf life of various drug products. Many drugs, especially biologics, are often lyophilized before they are packaged as a dry powder and then reconstituted and injected into patients. Lyophilization transforms a drug product from a liquid to a stable solid by removing water or other solvents. This technique is gaining popularity in the formulation development process because it extends the shelf life of small and large molecule drugs. BOC Sciences is a leader in commercial aseptic manufacturing and aseptic lyophilization of complex drug products. Our commercial facilities feature sterile lyophilization, providing a seamless process from development through production.
What is lyophilization technology?
Lyophilization technology refers to a commercially proven method developed by pharmacologists to stabilize formulations and therapeutic molecules. The process relies on controlling the pressure and temperature in a lyophilizer to remove liquid from formulations consisting of heat-sensitive or hydrolytically unstable active pharmaceutical ingredients or formulation components. The resulting solid gains greater stability than the aqueous solution, and it can be stored at higher temperatures than liquid precursors for longer periods of time.
Figure 1. Spray freeze dry process. (Weissmueller, N. T.; Marsay, L. et al. 2017)
Advantages of lyophilization
- Lyophilized biologics do not require expensive, complex logistics such as strict cold-chain regulatory validation systems and continuous documentable refrigeration at the pharmacy level
- Enhanced product stability in a dry state
- Enhanced stability of dry powders
- Removal of water without excessive heating of the product
- Quickly and easily dissolves reconstituted products
- Support shelf life
- Retain long-term potency
- Enable storage in ambient conditions
- Simplify transportation & storage
- Refine preparation of the administrable dosage form
Our Services
To make it easier and better for researchers, BOC Sciences provides lyophilization stability enhancement service in a competitive fashion. We have provided a more efficient way to increase the number of new drugs, greatly shorten the R&D cycle, and reduce the development costs. A growing number of products have benefited from the lyophilization process. BOC Sciences provides the equipment, formulation and analytical expertise and experience in developing, scaling up and validating lyophilization cycles to ensure projects have a chance of success
Figure 2. Exemplary lyophilization cycle during sublimation tests. (Chamberlain, R.; Schlauersbach, J. et al. 2020)
An integrated approach to lyophilization
- Specialized knowledge
We develop lyophilization cycles for each product by comprehensively understanding the freezing and drying behavior of the formulation components, as well as investigating how the formulation strength or container affects the freeze-drying process. If the lyophilized product contains other complex formulation ingredients such as nanoparticles, microparticles or liposomes, we provide additional formulation development and knowledge
- Sterile lyophilization
At BOC Sciences, our facility contains ISO Class 5 filling equipment for clinical and commercial production. In addition to aseptic filling and lyophilization capabilities, we can conduct particle size reduction and complex formulation activities under aseptic conditions. We also support in-situ cleaning and in-situ steam. Our teams perform extensive validation and monitoring of cleaning procedures for any lyophilization operation
- High capital investment
BOC Sciences have the equipment and personnel to develop and scale up aseptic lyophilization processes
Lyophilization process
1) Freezing: In this step, the water or solvent in the product is gradually frozen by the cooled shelves
2) Primary drying (sublimation): In this step, water is converted directly from a solid to a gas by sublimation
3) Secondary drying (desorption): In this step, the shelf temperature in the lyophilizer is gradually raised under low pressure to drive off any residual water or solvent
Figure 3. Sublimation tests -lyophilization cycle. (Chamberlain, R.; Schlauersbach, J. et al. 2020)
Capabilities for lyophilization process development and clinical trial manufacturing
- Our team of formulation experts use the development of experiments (DoE) methodology and the SMART approach to design the lyophilization cycle. This process is carried out in an iterative manner in parallel with product formulation development
- We thoroughly characterize the drug substance and lyophilized material to remove the necessary solvent molecules without damaging or degrading the target species
- For different materials, our teams apply different temperatures, sublimation rates, and processing steps and times to determine the ideal range for moisture content to be maintained during storage to prevent degradation, especially for formulations without stabilizers
- We carefully evaluate the reconstitution of the drug product which is a key evaluation parameter: Evaluation of various reconstitution media, the speed and reproducibility of reconstitution
- The lyophilization process development also includes the selection of the appropriate vessel/closure system. In addition, we perform compatibility studies with the selected container/closure system(s) upon selection of final formulation and process parameters
- Seamless transfer of process and operational parameters: At BOC Sciences, the optimized freezing, annealing, primary drying and secondary drying process parameters and operational parameters are designed to be easily transferred to clinical trial manufacturing or commercial product manufacturing facilities
Why choose BOC Sciences?
Our dedicated CMC team has provided tailored solutions to our clients from engagement to launch. With many years of industry experience, we provide clients with the following:
- Comprehensive, integrated CMC services with a flexible service model that grows with your programs
- Knowledgeable industry experts who deliver scalable, actionable insights
- World-class facilities and equipment that remain at the forefront of the global pharmaceutical research, analytical and development standards
- Our comprehensive services support products at every stage of the product lifecycle, from early-stage discovery to full commercial cGMP manufacture
- A focus on risk management that is designed to ensure completion of your technical goals
BOC Sciences provides professional, rapid and high-quality services of lyophilization stability enhancement at competitive prices for global customers. Personalized and customized services of lyophilization stability enhancement can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
References
- Weissmueller, N. T.; Marsay, L. et al. Alternative vaccine administration by powder injection: Needle-free dermal delivery of the glycoconjugate meningococcal group Y vaccine. PLOS ONE. 2017.
- Chamberlain, R.; Schlauersbach, J. et al. Freeze-drying in protective bags: Characterization of heat and mass transfer. European Journal of Pharmaceutics and Biopharmaceutics. 2020. 154: 309-316
