Continuous measurement of drying rate of crystalline and amorphous systems during freeze-drying using an in situ microbalance technique

✍ Scribed by Claudia Roth; Gerhard Winter; Geoffrey Lee

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 351 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1087

✦ Synopsis

The use of a novel microbalance (Christ) technique to monitor continuously the weight loss of a vial standing on a shelf of a freeze-dryer has been investigated. The drying rates of the following aqueous solutions were measured during the primary drying phase of a complete freeze-drying cycle: sucrose (75 mg/mL, 2.5-mL ®ll volume), sucrose and phenylalanine (1:0.2 by weight, 75 mg/mL, 2.5-mL ®ll volume), and mannitol (75mg/mL, 2.5-mL ®ll volume). The microbalance yields the cumulative water loss, m cu in grams, and the momentary drying rate, Dm cu /Dt in mg/10 min, of the frozen cake. The momentary drying rate curves were especially useful for examining how Dm cu /Dt changes with time during primary drying. Initially, Dm cu /Dt rises to a sharp maximum and then decreases in a fashion depending on shelf temperature, chamber pressure, and the nature of the substance being dried. Different drying behavior was observed for the sucrose and sucrose/phenylalanine systems, which was attributed to the presence of crystalline phenylalanine in the amorphous sucrose. At low shelftemperature (À248C) the crystalline mannitol showed lower Dm cu /Dt than with either sucrose or sucrose/phenylalanine. The balance could also detect differences in Dm cu /Dt when using different freezing protocols. Slow' and moderate' freezing protocols gave similar drying behavior, but `rapid' freezing in liquid nitrogen produced greatly altered drying rate and internal cake morphology. The balance also could be used to detect the endpoint of primary drying. Different endpoint criteria and their in¯uence on ®nal dried cake properties were examined.