Parenteral preparations filling volume

For colored glass containers, not intended for parenteral preparations, the measured transmission must not exceed a maximum value of 10% at any wavelength between 290 and 450 nm, irrespective of the size or glass type. The limits for colored glass containers, used for parenteral preparations, depend on their intended fill volume. The respective limits for these containers are given in Table 1 (3,4). 

The residual transmission of brown glass is recognized by both the European and the U.S. Pharmacopoeia. UV-VIS transmission values up to 10% are acceptable. In the case of parenteral preparations transmission values up to 50% are acceptable, depending on the product s fill volume. 

Class 100 areas are suitable to prepare, fill, and seal solutions that shall be sterilized but cannot be sterilized in their final containers (referring to no sterile-filtration before filling to filter, fill, and seal solutions of large volume parenterals fe50ml) that can be sterilized in their final containers to fill and stopper the vials of injectable powder and to refine, dry, and package sterile bulk pharmaceuticals and injectable powders. 

Many dry solid parenteral products, such as the cephalosporins, are prepared by sterile crystallization techniques. Control of the crystallization process to obtain a consistent and uniform crystal form, habit, density, and size distribution is particularly critical for drug substances to be utilized in sterile suspensions. For example, when the crystallization process for sterile ceftazidime pentahydrate was modified to increase the density and reduce the volume of the fill dose, the rate of dissolution increased significantly. 

An example of the second method of parenteral suspension preparation is testosterone suspension. Here, the vehicle is prepared and sterile-filtered. The testosterone is dissolved separately in acetone and sterile-filtered. The testosterone-acetone solution is aseptically added to the sterile vehicle, causing the testosterone to crystallize. The resulting suspension is then diluted with sterile vehicle, mixed, the crystals allowed to settle, and the supernatant solution siphoned off. This procedure is repeated several times until all the acetone has been removed. The suspension is then brought to volume and filled in the normal manner. 

Handling and filling of aseptically prepared products, including small and large volume parenterals, should be done in a Grade A environment with a Grade background. 

To make parenterals ready to administer, sometimes dilutions are to be made (see also Chap. 13). The deviation of the volume to be measured decreases with the increasing degree of filling of the syringe used. From the viewpoint of the pharmaceutical preparation a deviation of no more than 5-10 % is recommended (see Sect. 29.1.1). This recommendation, however, may require an additional dilution step to be performed. This increases the risk of microbiological contamination and calculation errors. Therefore risk assessment is necessary to decide which measurement accuracy is accepted in practice. 

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