Expert Lyophilized Drug Formulation Development
Improve stability and long-term potency of your pharmaceutical product with our lyophilization formulation development. Our team helps prepare your drug formulation for reliable manufacturing, storage, handling, and administration. We focus on pairing your product with the most compatible excipients and ensuring your final drug product is prepared for an array of conditions.
Our Development Process
Numerous factors require consideration when developing a lyophilized drug product, including the choice of excipients, the freezing rate, the primary drying temperature and time, and the secondary drying temperature and time. Our formulation experts apply their extensive experience in developing lyophilized drug products to help you to select the appropriate formulation and process parameters suitable for your compound.
Lyophilization process development requires thorough drug substance and lyophilate characterization. Our team applies comprehensive experience to investigate critical aspects of your molecule and materials before lyophilization for optimal drug product stability. For example, we use differential scanning calorimetry and freeze-dry microscopy for liquid product thermal characterization. These analyses help determine the target product temperature during primary drying to prevent product collapse or melt.
After the primary drying cycle, our team leverages Karl Fischer titration and differential scanning calorimetry for information on the final product’s residual moisture and glass transition temperature, informing possible accelerated stability conditions. We also use secondary drying as an opportunity to pull vials with a sample thief to gauge stability across a range of residual moisture levels and set final product specifications.
Different excipients provide varying benefits to the stability of your product. Our team helps produce an elegant and shelf-stable drug product by striking the optimal balance between cryoprotectants, lyoprotectants, surfactants, and glass transition modifiers. This process requires an understanding of the molecule’s primary modes of degradation as well as the mechanism of protection provided by each formulation component.
Lyophilized Drug Product Formulation Factors
Formulation composition is a foundational aspect of your drug product that impacts product stability and the development of the lyophilization cycle. Your choice of materials provides varying mechanisms of protection and requires different temperatures and processing steps during lyophilization. We provide guidance to navigate these product development considerations and help determine the ideal range for moisture content to maintain during storage to prevent degradation.
As drug product reconstitution is a key evaluation parameter, we assess the speed and reproducibility of reconstitution throughout process development. Various reconstitution media may be evaluated.
Lyophilization process development includes the selection of the appropriate container/closure system. Based on the optimal pre-lyophilization concentration and target unit dose, an appropriately sized primary container is then chosen to allow for the most efficient cycle to minimize production time. Additionally, we conduct compatibility studies with the selected container/closure system(s) upon selection of final formulation and process parameters.
The developed lyophilization cycle parameters include freezing, annealing, primary drying, and secondary drying, which are tested for robustness and transfer seamlessly to clinical or commercial-scale manufacturing sites.
Diverse Molecular Support
Lipid nanoparticle (LNP) formulations are prone to aggregation and particle disruption during lyophilization. A comprehensive analytical package, including particle and payload characterization, allows for a thorough excipient screening to reach an optimal formulation for each unique lipid combination.