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Is Spray Drying a Viable Alternative to Lyophilization?
Lyophilization, or freeze drying, is the most common processing method for removing moisture from biopharmaceuticals, and it can increase the stability, temperature tolerance, and shelf life of these products. Although lyophilization is well established within the industry, it requires expensive equipment that takes up a great deal of space within a production facility. Lyophilization also can take days to complete, and manufacturers that need a powdered product must incorporate a granulation step to the process. In an environment where budgets are tightening, and where time and facility space are at a premium, lyophilization might be a difficult option for some companies.
Spray drying is an alternative technique for preserving biopharmaceuticals, but it is relatively new to the industry. Equipment and Processing Report (EPR) talked to Satoshi Ohtake, research and development scientist at Aridis Pharmaceuticals (San Jose, CA), to find out when spray drying might be a reasonable alternative to lyophilization.
EPR: What is spray drying? How is the process performed?
Ohtake: Spray drying is a process whereby a liquid formulation is converted into a dry powder in a single step. The process is typically performed by first atomizing the solution into fine droplets that are then dried quickly in a large chamber by using warm gas. The resulting dry particles are collected with a cyclone.
EPR: What process conditions must be maintained for spray drying to be successful?
Ohtake: The solution feed rate, the atomization pressure, and the outlet temperature, to name a few. All of these parameters affect the stability of the biopharmaceutical and are correlated with each other. If fast drying is desired, then the solution feed rate can be decreased, and atomization pressure increased. This way, the evaporative load is lower, and droplets are made smaller. By coupling that effect with high outlet temperature, the drying kinetics can be increased.
EPR: What challenges does the spray-drying process pose?
Ohtake: Spray drying exposes biopharmaceuticals to shear stress during the atomization step, which could destabilize labile biopharmaceutical compounds such as proteins. Complex biological molecules are difficult to spray dry because they are sensitive to high shear stress. The amount of shear stress encountered depends on the type of atomizer and the amotmization pressure used. At our facility, we use a sonic nozzle that can operate at a relatively low pressure of less than 20 psig, which minimizes the shear stress and allows us to process complex biopharmaceuticals such as vaccines.
EPR: For what kinds of biopharmaceuticals would spray drying be appropriate?
Ohtake: Spray drying has been conducted for a wide variety of biopharmaceuticals. Aridis has successfully spray dried proteins, enzymes, antibodies, viruses, and bacteria.
EPR: How can spray drying increase a biopharmaceutical’s stability, temperature tolerance, or shelf life?
Ohtake: The process removes water and restricts the biopharmaceutical’s mobility, which results in a significantly lowered degradation rate.
EPR: Does spray drying stabilize a product to the same extent as lyophilization does?
Ohtake: It depends. The fact that the end product in each case is a dried biopharmaceutical stabilized in an excipient matrix suggests that the stability profiles will be similar. However, we have observed significant differences between the storage stability of the same biopharmaceutical processed by spray drying and freeze drying. One of the reasons is the difference in the way the biopharmaceutical was dried. Another reason may be that the physical properties of the final dry product are significantly different. The processes’ relative abilities to increase stability, however, depend highly on the biopharmaceutical. In one study of manufacturing a dry powder viral vaccine, lyophilization resulted in the worst stability profile of all drying processes examined. On the other hand, lyophilization produced a more stable dry bacterial vaccine than spray drying did.
EPR: Does spray drying have advantages over lyophilization?
Ohtake: The main advantage of spray drying over freeze drying is that it makes particle engineering more feasible. By manipulating the conditions of the spray-drying process, manufacturers can adjust various particle properties such as size distribution, dispersibility, and surface enrichment of biopharmaceuticals. The size of freeze-dried biopharmaceuticals can only be reduced by milling.
In many instances, it is advantageous to have the dry biopharmaceutical in a powder format, which facilitates its conversion into capsules, tablets, and thin films. In that sense, spray drying is a convenient one-step process that converts the biopharmaceutical directly from a liquid to a powder. Lyophilization, on the other hand, requires a milling step. Another advantage is scalability. Spray drying is more scalable at lower costs with regards to equipment, facility, and utilities. Furthermore, the cycle time for spray drying is hours instead of days, and thus operational costs can be lower than those for lyophilization.
EPR: When might lyophilization be preferred to spray drying?
Ohtake: Lyophilization might be preferred for a single-dose, injectible biopharmaceutical that requires reconstitution. Vials can be enclosed aseptically at the end of this process, whereas spray-dried powders must be distributed into vials or blister packs using another instrument. The choice of process is determined partly by the final dosage format and partly by the biopharmaceutical’s sensitivity to temperature and shear.