凍結乾燥品に及ぼす, セファロチンナトリウム過飽和溶液への物理的刺激の影響(第2報)

抄録

Seeding and subsequent freeze-drying of aqueous cephalothin sodium (CET-Na) solution of supersaturated concentrations, which preliminarily received an excess of mechanical stress, have been reported to make the product unacceptable in pharmaceutical elegance and in chemical stability upon storage. In order to find out the cause, the CET-Na solution that preliminarily received mechanical stress has been examined as to its crystallization behavior during freezedrying process, by using polarizedlight cryomicroscopy, scanning electron microscopy, cryodifferential scanning calorimetry, refractometry, viscositometry, and surface tensiometry. Aqueous CET-Na solution of supersaturated concentrations, to which an excess of mechanical stress was given, has been demonstrated to exhibit the following features : in the process of seeding and subsequent freeze-drying, the solution shows an incomplete crystallization at -40°C ; in the crystal growth stage at -5°C, crystals are found to be difficult to grow sufficiently from the seeds as their nuclei. These findings indicate that the supersaturated solution has changed to an unusual state upon receiving such stress, the state being different from the state of untreated solution in that the solution thus treated shows physico-chemical properties capable of easy crystallization through a simple step of freezing. The change as such in physico-chemical properties has also been estimated to have resulted from a structural change of associated molecules of CET-Na in its supersaturated solution into a condensed state quite similarly to that of liquid crystals.