Formulation of stable protein powders by supercritical fluid drying

摘要: Protein pharmaceuticals are potent drugs for the treatment of several chronic and life-threatening diseases. However, complex sensitive nature protein molecules requires special attention in development stable dosage forms. Developing aqueous formulations is often a problem. Dried have been successfully used to overcome instability drug during shipping long-term storage. Among drying processes available, lyophilization, or freeze-drying, most commonly technique pharmaceuticals. lyophilization an expensive, time- energy-consuming process. Furthermore, some proteins susceptible damage freezing step freeze-drying not method choice if microparticulate powders with well-defined particle characteristics needed, e.g., pulmonary delivery. Supercritical fluid (SCF) has proposed as alternative lyophilization. SCF fast process capable producing powders. In bypassed, but factors like mixing, mass transport rates, droplet formation composition can play crucial role kinetics properties dried products, well excipients. The aim this thesis was investigate capability stabilization. primary goal gain new fundamental insights into effect processing formulation parameters on stability after from solution, storage reconstitution. particular, relationships between parameters, product were studied identify critical successful stabilization by drying. To end, we selected readily available model (lysozyme, myoglobin, IgG) various physicochemical characteristics. results presented show that embedded amorphous carbohydrate matrix. Some general recommendations established shown be valid well. Firstly, addition sugar (e.g., sucrose, trehalose) prevents aggregation solid state Secondly, matrix high glass transition temperature preferred avoid crystallization, which detrimental proteins. Stabilizers yielded matrices. sucrose more difficult powder. Designing obtain turned out delicate interplay excipient selection optimization. important Although reported necessary solutions, use ethanol stability. Unexpectedly levels residual had plasticizing effect, resulted crystallization We showed it possible dry without any other co-solvent formulations.