Application of in-line viscometer for in-process monitoring of microcrystalline cellulose-carboxymethylcellulose hydrogel formation during batch manufacturing

摘要

Physical stability and consistent dose delivery of pharmaceutical suspension formulations comprised of microcrystalline cellulose (MCC) and sodium carboxymethylcellulose (NaCMC) hydrogels is dependent on their rheological properties. To obtain the desired rheological characteristics, good control of the hydrogel dispersion in water is required. The goal of this study was to evaluate whether the XL7-100 Process Viscometer could be employed as a process analytical technology (PAT) tool to monitor the dispersion process in real time during batch manufacturing. Using this instrument, viscosity profiles were measured during the hydrogel processing for a range of operating conditions. It was confirmed that viscosity obtained by the XL7-100 Process Viscometer in the off-line mode, could be linearly correlated to that of the conventional Brookfield viscometer. In addition, the XL7-100 Process Viscometer was able to detect variations in the hydrogel concentrations as well as process conditions in real time. Under fixed operating conditions, the dynamic viscosity profile showed low variability and good inter-batch reproducibility for a properly dispersed hydrogel. For a well-validated mixing process, an off-trend in-line viscosity reading may be indicative of batch failure or poor dispersion homogeneity. Therefore, the in-line viscometer can be used in manufacturing to monitor the batch to batch consistency. However, it is not proven to be able to characterize the real-time structure formation of the hydrogel. It is recommended that the in-line viscometer be used as a complimentary tool along with the off-line rheometer for both efficient and effective in-process quality control of the MCC & NaCMC hydrogel dispersion.