Microporous sterilizing filters

Water-soluble drugs are usually also hygroscopic, and need to be stored in an anhydrous environment to maintain their stability. These are most easily supplied as lyophilized powders, which can be reconstituted with water or saline immediately prior to injection. This applies to early development as well, when the filtration of drug solution through micropore nylon filters prior to lyophiliza-tion can be a convenient way to ensure sterility. Lyophilizates in stoppered vials can also be subjected to 7-irradiation to ensure sterility. Stability studies should include not only the range of temperatures and humidities (see below), but also with the vials inverted. 

Because membrane filtration is the only currently acceptable method of sterilizing protein pharmaceuticals, the adsorption and inactivation of proteins on membranes is of particular concern during formulation development. Pitt [56] examined nonspecific protein binding of polymeric microporous membranes typically used in sterilization by membrane filtration. Nitrocellulose and nylon membranes had extremely high protein adsorption, followed by polysulfone, cellulose diacetate, and hydrophilic polyvinylidene fluoride membranes. In a subsequent study by Truskey et al. [46], protein conformational changes after filtration were observed by CD spectroscopy, particularly with nylon and polysulfone membrane filters. The conformational changes were related to the tendency of the membrane to adsorb the protein, although the precise mechanism was unclear. 

The substrate can be filled into a number of different containers. Mason jars, polypropylene jars or high density, heat-resistant polyethylene bags are commonly employed. The containers are closed and sealed with a microporous filter. They are sterilized at 1 5 psi for 60-90 minutes. After sterilization the containers are cooled to ambient temperature and inooulated. The inoculum can be either grain spawn or sawdust-bran spawn. 

---