A molecule of a biological medicine is commonly a protein made of a chain of several hundred amino acids with a complex three-dimensional structure. The protein drugs should remain stable for several years, maintaining the active conformation, even under unfavorable conditions during transport or storage. Freeze drying is one of the most common formulation methods of protein drugs. However, it does not lead to well-defined microparticles and is a comparatively expensive and timeconsuming process.Spray drying is a method with a high potential and attractive alternative in preparation of solid pharmaceutical substances by freeze drying [1,2]. However, spray drying is often regarded as a harsh drying method, because bio-molecules encounter several denaturation stresses as mentions in the following section. There are several factors which result in the substantial inactivation of enzyme protein during spray drying. Therefore, it is important to develop new formulation concept for encapsulation and stabilization of proteins during spray drying [3,4]. In this review the recent development of the applications of spray drying to protein solution will be reviewed, concentrating on the formulation of protein solution and the operational conditions of spray drying [5].
Protein Denaturation Stress Suffered in Spray Drying ProcessSpray dr ying of various protein solutions results in substantial inactivation caused by many stresses in the drying process. The possible stress factors in the spray dr ying system are schematically shown in Fig. 1 [6].Proteins have a tendency to denature and undergo irreversible aggregation during various steps of spray drying. At first, proteins are presumably exposed to high mechanical shear stress in the flow line and the atomiza-The protein drugs should remain stable for several years even under unfavorable conditions during transport or storage. There are several methods for the production of the protein drugs, including freeze dr ying and spray dr ying. Spray dr ying is a method with a high potential and attractive alternative in preparation of solid pharmaceutical drugs by freeze drying. Spray drying is often regarded as a harsh drying method due to the surface induced denaturation of bio-molecules during processing, since atomization and subsequent drying could potentially be detrimental to heat sensitive biological materials such as enzyme. Therefore, it is important to develop new formulation concept for encapsulation and stabilization of proteins during spray dr ying. This article reviewed several factors which result in the substantial inactivation of enzyme protein during spray dr ying, including the operational conditions of spray drying, the formulation of the feed enzyme solution and additives.