PT - JOURNAL ARTICLE AU - Yasuto Koyama AU - Madhav Kamat AU - Robert J. De Angelis AU - Ram Srinivasan AU - Patrick P. DeLuca TI - Effect of Solvent Addition and Thermal Treatment on Freeze Drying of Cefazolin Sodium DP - 1988 Mar 01 TA - PDA Journal of Pharmaceutical Science and Technology PG - 47--52 VI - 42 IP - 2 4099 - http://journal.pda.org/content/42/2/47.short 4100 - http://journal.pda.org/content/42/2/47.full SO - PDA J Pharm Sci Technol1988 Mar 01; 42 AB - Due to the spontaneous and many times incomplete freezing of water upon supercooling aqueous cefazolin sodium (CEZ) solutions, CEZ fails to crystallize readily. Unless thermally treated at a temperature in the vicinity of the crystallization exotherm, the drying is impeded and the resultant freezedried material will be in the less stable amorphous form. Thermal treatment for 24 hours was required to produce dried material showing appreciable crystallinity by X-ray diffractometry. The inclusion ofisopropyl alcohol (IPA) as a co-solvent before freezing induced crystallization of the amorphous form both with and without thermal treatment. Comparison of various conditions for scaled-up batches of CEZ showed that the use of thermal treatment of–10°C for one hour in the presence of 5% w/w IPA yielded crystalline dried product and the drying cycle was shortened considerably over the regular freeze-drying method. Nitrogen bleed to maintain a chamber pressure of 150 ¡iHgfurther reduced the drying cycle time. With IPA as a co-solvent it was possible to utilize a shelf temperature of 45°C during primary drying and achieve a 100% yield of acceptable vial