Antibiotics, Cytostatics, Ibuprofen

The freeze-drying of antibiotics and blood serum largely represented the beginning of industrial lyophibzation. Neumann [3.34] wrote in 1952, The (freeze-drying) temperature for the older, not well purified penicilhn preparations had to be kept surprisingly low... it could not exceed -25 or —40 °C and later, Today penicillin is manufactured as crystals without the need for freeze-drying . 

Other antibiotics still require freeze-drying, e.g. Na-cephalotin (Na-CET). Takeda [1.32] showed that thermal treatment of Na-CET was not sufficient to produce a pure crystalline product, as the amorphous fraction discolors during storage and must be avoided. Takeda described the production of pure crystalline Na-CET by adding microcrystals of Na-CET to a saturated solution of Na-CET. If this mixture was frozen and freeze-dried, then no amorphous or quasi-crystalline forms were found. Koyama et al.[3.35] reported that after thermal treatment for 24 h some parts remained incompletely crystallized. After adding 5% w/w isopropyl alcohol, a thermal treatment of 1 h was sufficient Furthermore, the product could be dried at a higher pressure. Thus the drying time could be reduced and 100% of the product could be used. 

Ikeda [3.36] presented a two-stage freezing process for an antibiotic (panipenem), which reacts with another component of the drug (betamipron) and has therefore to be separated until its use. The first substance is filled into vials and frozen. The precooled second substance is then filled into cooled vials and frozen. By this process, the amount of undesirable reaction product could limited to 0.5% during a 6 months 

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