A Study on the Impact of Hydroxypropyl Methylcellulose on the Viscosity of PEG Melt Suspensions Using Surface Plots and Principal Component Analysis

摘要

An understanding of the rheological behaviour of polymer melt suspensions is crucial in pharmaceutical manufacturing, especially when processed by spray congealing or melt extruding. However, a detailed comparison of the viscosities at each and every temperature and concentration between the various grades of adjuvants in the formulation will be tedious and time-consuming. Therefore, the statistical method, principal component analysis (PCA), was explored in this study. The composite formulations comprising polyethylene glycol (PEG) 3350 and hydroxypropyl methylcellulose (HPMC) of ten different grades (K100 LV, K4M, K15M, K100M, E15 LV, E50 LV, E4M, F50 LV, F4M and Methocel VLV) at various concentrations were prepared and their viscosities at different temperatures determined. Surface plots showed that concentration of HPMC had a greater effect on the viscosity compared to temperature. Particle size and size distribution of HPMC played an important role in the viscosity of melt suspensions. Smaller particles led to a greater viscosity than larger particles. PCA was used to evaluate formulations of different viscosities. The complex viscosity profiles of the various formulations containing HPMC were successfully classified into three clusters of low, moderate and high viscosity. Formulations within each group showed similar viscosities despite differences in grade or concentration of HPMC. Formulations in the low viscosity cluster were found to be sprayable. PCA was able to differentiate the complex viscosity profiles of different formulations containing HPMC in an efficient and time-saving manner and provided an excellent visualisation of the data.