Characterization of Lyophilized Drug Products
Determination of Solid-State Structures by differential scanning calorimetry (DSC)
At HTD, we use differential scanning calorimetry (DSC) as part of our solid-state characterization services to study the thermodynamic properties of solids. DSC measures the heat flow into or out of a sample as it is heated or cooled, and it is based on the principle that the heat flow is influenced by the changes in the physical, chemical, and biological properties of the sample.
Using DSC, we can determine the melting temperature and enthalpy of melting of solids, as well as their thermal stability and degradation behavior. This information is important for understanding the stability and performance of solids and for developing stable and consistent products.
Through our collaborators, we use DSC in combination with other techniques, such as X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), to provide a comprehensive understanding of the solid-state properties of a sample. This information is useful for optimizing the formulation and processing of solids and for identifying any potential issues that may arise during storage or use.
Overall, DSC is a valuable tool for the characterization of solids, and our team of scientists is skilled in its use and interpretation. We use DSC as part of our solid-state characterization services to support the development and optimization of solid forms of therapeutic agents.
Determination of Residual Moisture Content
Karl Fischer's coulometric moisture analysis is a technique that we use at HTD to accurately and precisely measure the moisture content of solids and liquids. The Karl Fischer method is based on the principle that water reacts with iodine to form hydriodic acid (HI), which can be quantitatively determined by measuring the amount of electricity required to generate the reaction.
The Karl Fischer method has several advantages over other moisture analysis techniques, including its accuracy, sensitivity, and wide dynamic range. It is capable of measuring moisture contents from as low as a few parts per million (ppm) to as high as 100% humidity, making it suitable for a wide range of applications.
We use Karl Fischer's coulometric moisture analysis as part of our solid state characterization and stability testing services to assess the moisture content of solids and liquids. This information is important for understanding the stability and storage conditions of the product and for identifying any potential issues that may arise during storage.
Determination of Reconstitution Time of Lyophilized cakes
At HTD, we use a range of techniques to determine the reconstitution time of lyophilized cakes, which is the time it takes for the cake to fully rehydrate after being reconstituted with a solvent. Reconstitution time is an important parameter in the development of lyophilized products, as it impacts the product's stability, ease of use, and convenience for patients.
One technique we use to determine the reconstitution time of lyophilized cakes is visual inspection. This involves observing the cake as it is reconstituted and noting the time at which it is fully rehydrated. Visual inspection is a simple and rapid method that can provide a rough estimate of the reconstitution time. Based on this information, our experts will adjust the lyophilization cycle to optimize the reconstitution time.
Lyophilized cake structure refers to the physical structure of the lyophilized product after it has been subjected to the freeze drying process. The structure of the lyophilized cake can have a significant impact on the stability, performance, and convenience of the product, and it is therefore an important consideration in the development of lyophilized products.
The structure of the lyophilized cake can be influenced by a number of factors, including the properties of the product (e.g., concentration, viscosity, and glass transition temperature), the lyophilization process (e.g., primary and secondary drying conditions), and the excipients used (e.g., bulking agents, stabilizers, and process aids).
There are several characteristics of the lyophilized cake structure that are commonly evaluated, including:
Pore size: The size and distribution of the pores in the lyophilized cake can influence the rate and extent of water uptake during reconstitution and the stability of the product during storage.
Porosity: The porosity of the lyophilized cake is a measure of the volume of voids in the cake and can impact the flowability and compressibility of the product.
Density: The density of the lyophilized cake is a measure of the mass per unit volume of the cake and can influence the flowability and reconstitution properties of the product.
Surface roughness: The surface roughness of the lyophilized cake can impact the wettability of the cake and the ease of reconstitution.
Overall, the structure of the lyophilized cake is an important aspect of the development of lyophilized products, and our team of protein scientists is skilled in the evaluation and optimization of lyophilized cake structure.
Visual Inspection of Lyophilized Cakes
Prevention of Collapse
Visual inspection of lyophilized cakes is a simple and rapid method for evaluating the appearance and physical properties of the product. It involves visually examining the lyophilized cake and noting any defects or abnormalities, such as cracks, pores, or surface roughness.
Visual inspection can provide valuable information on the quality and consistency of the lyophilized cake, and it is often used in combination with other techniques (e.g., gravimetry, spectroscopy) to provide a comprehensive understanding of the product.
One important aspect of visual inspection of lyophilized cakes is the prevention of collapse, which refers to the collapse or shrinkage of the cake during the lyophilization process or during storage. Collapse can be caused by a variety of factors, including insufficient drying, inadequate vial closure, or changes in temperature or humidity.
To prevent collapse, it is important to optimize the lyophilization process and the storage conditions of the product. This may involve using appropriate vial closure systems, controlling the temperature and humidity of the storage environment, and using stabilizers and other excipients to improve the stability of the product.