Effect of stopper processing conditions on moisture content and ramifications for lyophilized products: comparison of "low" and "high" moisture uptake stoppers.

The purpose of this study was to evaluate the effect of processing and storage on the moisture content of two commercially available, 13-mm lyophilization stoppers designated as low moisture (LM) and high moisture (HM) uptake stoppers. The stopper moisture studies included the effect of steam sterilization time, drying time and temperature, equilibrium moisture content, lyophilization and moisture transfer from stopper to a model-lactose lyophilized cake. Results indicated that both stoppers absorbed significant amounts of moisture during sterilization and that the HM stopper absorbed significantly more water than the LM stopper. LM and HM stoppers required approximately 2 and 8 h drying at 105 degrees C, respectively, to achieve final moisture content of not more than 0.5 mg/stopper. Following drying, stopper moisture levels equilibrated rapidly to ambient storage conditions. The apparent equilibrium moisture level was approximately 7 times higher in the HM versus LM stopper. Freeze-drying had minimal effect on the moisture content of dried stoppers. Finally, moisture transfer from the stopper to the lyophilized product is dependent on the initial stopper water content and storage temperature. To better quantify the ramifications of stopper moisture, projections of moisture uptake over the shelf life of a drug product were calculated based on the product-contact surface area of stoppers. Attention to stopper storage conditions prior to use, in addition to processing steps, are necessary to minimize stability issues especially in low-fill, mass lyophilized products.

Instrumentation of a high-shear mixer: evaluation and comparison of a new capacitive sensor, a watt meter, and a strain-gage torque sensor for wet granulation monitoring.

A high-shear mixer was instrumented with a new capacitive sensor, a watt meter, and a strain-gage torque sensor. The output from the capacitive sensor was split into two channels, which monitor both resistive and capacitive changes during the granulation process. The outputs of the devices were related to properties of the wet granulation. The percentage moisture content related linearly to the amplitude channel response. Yield values provided a rheological property to relate with power consumption and torque measurement. Power consumption and torque furnished a similar map of the granulation process. The amplitude channel of the capacitive sensor appears to be more clearly differentiated between binder levels in hydrous lactose-HPMC granulations than either power consumption or torque measurement, based on particle size distributions.