Long-term stability in aqueous matrix, due to hydrolysis and other mechanisms of degradation, is not always optimal and can be difficult to maintain. Final dosage forms are frequently lyophilized to improve the stability, the shelf life, long-term potency, and may enable storage at ambient conditions to simplify transportation, storage, and preparation of the administrable dosage form.
Development of the lyophilization process requires a thorough characterization of the drug substance (small molecule or biologic) and lyophilates in order to remove the necessary solvent molecules without disrupting or degrading the target species. Our team of formulation experts design lyophilization cycles using both the DOE approach and SMART technology and it is performed in an iterative manner in parallel with product formulation development.
The formulation composition impacts the development of the lyophilization cycle in that different materials require different temperatures, sublimation rates, and processing steps and duration. The ideal range for moisture content must be determined and maintained during storage to prevent degradation, particularly for formulations without stabilizers. As reconstitution of the drug product is a key evaluation parameter, the speed and reproducibility of reconstitution will be assessed throughout process development. Various reconstitution media may be evaluated. Lyophilization process development also includes the selection of the appropriate container/closure system. We conduct compatibility studies with the selected container/closure system(s) on selection of final formulation and process parameters.
The optimized, the freezing, annealing, primary drying and secondary drying process parameters and operational parameters are an easy technology transfer to our clinical trials manufacturing site in Salem, New Hampshire, or the commercial product manufacturing facility.