The lyophilization process consists of three main stages: freezing, primary drying, and secondary drying.
Freezing: During the freezing stage, the product is cooled to a temperature below its glass transition temperature (Tg) in order to freeze it and remove the water by sublimation. The rate and extent of freezing can be influenced by the temperature, humidity, and air flow conditions in the freeze dryer, as well as the product properties (e.g., concentration, viscosity, and Tg).
Primary drying: During the primary drying stage, the product is subjected to a drying process to remove the remaining water. This can be achieved by either decreasing the pressure in the freeze dryer (vacuum drying) or increasing the temperature (thermal drying). The primary drying stage is important for achieving a high degree of water removal and for forming a solid glass.
Secondary drying: During the secondary drying stage, the product is subjected to further drying in order to reduce the moisture content to the desired level. This can be achieved by either decreasing the pressure in the freeze dryer (vacuum drying) or increasing the temperature (thermal drying). The secondary drying stage is important for achieving the desired moisture content and for optimizing the stability and performance of the lyophilized product.
Overall, lyophilization cycle development involves the optimization of the freezing, primary drying, and secondary drying stages to produce high-quality lyophilized products that meet the needs of our clients.
Lyophilization Cycle Optimization
Lyophilization cycle optimization involves the design and optimization of the freeze-drying process to produce high-quality lyophilized products that meet the needs of our clients. There are several key parameters that can be optimized in the lyophilization cycle, including:
- Primary drying temperature: The primary drying temperature is the temperature at which the primary drying stage is carried out. It can influence the rate and extent of water removal and the stability of the product during storage.
- Primary drying pressure: The primary drying pressure is the pressure at which the primary drying stage is carried out. It can influence the rate and extent of water removal and the stability of the product during storage.
- Primary drying duration: The primary drying duration is the length of time that the primary drying stage is carried out. It can influence the rate and extent of water removal and the stability of the product during storage.
- Secondary drying temperature: The secondary drying temperature is the temperature at which the secondary drying stage is carried out. It can influence the moisture content of the product and the stability of the product during storage.
- Secondary drying pressure: The secondary drying pressure is the pressure at which the secondary drying stage is carried out. It can influence the moisture content of the product and the stability of the product during storage.
- Secondary drying duration: The secondary drying duration is the length of time that the secondary drying stage is carried out. It can influence the moisture content of the product and the stability of the product during storage.
- Freezing and sublimation rates: The freezing and sublimation rates are the rates at which the product is cooled and dried during the lyophilization process. They can influence the stability and performance of the product.
Lyophilization cycle optimization involves the optimization of these and other parameters to produce high-quality lyophilized products that meet the needs of our clients. Our team of protein scientists is skilled in the optimization of lyophilization cycles and is dedicated to providing high-quality services to our clients.
Excipients for lyo formulation development
Excipients are inactive ingredients that are used in lyophilized protein formulations to improve the stability, performance, and convenience of the product. Excipients can be classified into several categories, including bulking agents, stabilizers, and process aids.
Bulking agents are excipients that are used to increase the volume of the lyophilized cake and improve the flowability of the product. Examples of bulking agents include lactose, mannitol, and maltodextrin.
Stabilizers are excipients that are used to protect the protein from degradation and to improve its stability during storage. Examples of stabilizers include sugars (e.g., sucrose, trehalose), amino acids (e.g., arginine, histidine), and surfactants (e.g., polysorbates, lecithin).
Process aids are excipients that are used to facilitate the lyophilization process and improve the performance of the product. Examples of process aids include cryoprotectants (e.g., glycerol, polyethylene glycol), pH buffers (e.g., sodium phosphate, acetate), and osmolality adjusters (e.g., sodium chloride, mannitol).
Overall, excipients play an important role in the development of lyophilized protein formulations, and our team of protein scientists has extensive experience in the selection and optimization of excipients for specific applications.
Polysorbate is a type of surfactant that is often used as an excipient in lyophilized protein formulations. It is a non-ionic surfactant that can improve the stability and performance of proteins by reducing the surface tension of the solution and preventing protein aggregation. Polysorbate can also improve the flowability and wettability of the lyophilized cake and facilitate the reconstitution process.
Polysorbate is generally considered to be a safe and effective excipient, but it can potentially interfere with certain proteins or assays. It is important to carefully evaluate the suitability of polysorbate for a specific application and to optimize its concentration and use as needed.
Our team of protein scientists has experience in the use of polysorbate as an excipient in lyophilized protein formulations, and we can support the development and optimization of formulations that incorporate this surfactant.
Primary Glass Transition Temperature
At HTD, we use the primary glass transition temperature (Tg) as an important parameter in the development of lyophilization cycles. Tg is the temperature at which a solid transitions from a glassy to a rubbery state, and it is a key factor in the stability and performance of lyophilized products.
During the lyophilization process, the product is cooled to a temperature below its Tg in order to freeze it and remove the water. The product is then subjected to a drying process to remove the remaining water, and it is cooled again to a temperature below its Tg to form a solid glass.
The primary Tg is the Tg of the product in its frozen state, and it is important for understanding the stability and performance of the product during storage and reconstitution. A product with a low primary Tg is more prone to physical changes during storage, such as crystallization or amorphous aggregation, which can impact its stability and performance.
In our lyophilization cycle development services, we use a range of techniques, including DSC and spectroscopy, to determine the primary Tg of lyophilized products. We also use these techniques to optimize the lyophilization cycle and ensure the stability and performance of the lyophilized product.
Eutectic Temperature
The eutectic temperature is the temperature at which a mixture of two or more substances forms a solid solution, and it is a key parameter in the development of lyophilized products. The eutectic temperature is typically lower than the individual melting points of the component substances, and it is important for understanding the stability and performance of the product during storage and reconstitution.
In the context of lyophilization, the eutectic temperature can be used to optimize the freezing stage of the process. By cooling the product to a temperature below its eutectic temperature, it is possible to achieve a more rapid and complete freezing of the product, which can improve the efficiency and quality of the lyophilization process.
The eutectic temperature can be determined by measuring the melting point of the product mixture using techniques such as differential scanning calorimetry (DSC). It is important to carefully evaluate the eutectic temperature of the product mixture in order to optimize the lyophilization process and ensure the stability and performance of the lyophilized product.
