Development and Evaluation of a Laboratory-Scale Apparatus to Simulate the Scale-Up of a Sterile Semisolid and Effects of Manufacturing Parameters on Product Viscosity

Abstract

The purpose of this study was to develop a benchtop apparatus to simulate the scale-up of the moist-heat sterilization process of sodium carboxymethylcellulose (CMC) gel and identify critical process parameters that affect the sterilized gel viscosity. A 600-ml benchtop Parr reactor was modified and used to achieve good correlation with a previously established heating profile using different equipment at the manufacturing site. The Parr reactor is constructed with 316 stainless steel, pressure rated to 2000 psig, and temperature rated to 350°C. After several trials, a low-wattage heater (300 W) was determined to be suitable for this sterilization process (122°C for 20 min). An anchor stirrer was installed for more efficient mixing while the gel was being sterilized. Evacuation and nitrogen flushing of the vessel could easily be performed through the gas inlet valves. The temperature controller (model 4843) has a microprocessor-based control module that provides a temperature profile control with adjustable tuning parameters. This apparatus was used to mimic the full-scale sterilization process by simulating the production sterilization temperature profile. Using this device, we found that the critical process parameters that affected final product viscosity were heating time, the starting pressure, residual oxygen concentration in the vessel, and the inherent viscosity of the CMC raw material. This study indicated that it is possible to use the Parr reactor to simulate the scale-up sterilization process of a semisolid product. A product with a consistent viscosity range could be manufactured by controlling critical process parameters during sterilization.