Probing the impact of HPMC viscosity grade and proportion on the physical properties of co-freeze-dried mannitol-HPMC tableting excipients using multivariate analysis methods

Abstract

This study investigated the impact of hydroxypropyl methylcellulose (HPMC) viscosity grade, HPMC proportion and particle size fraction on the physical properties of the freeze-dried mannitol-HPMC excipients produced, using multivariate analysis methods. Solutions containing 20%, w/w mannitol-HPMC were freeze-dried and milled to obtain excipients of size fractions 125–355 μm and 355–710 μm to understand the impact of the formulation variables on the molecular, particle and bulk properties of the excipients. Results showed that the freeze-dried mannitol-HPMC excipients were mainly differentiated by 3 overarching properties, in the order of their contribution to the variation in the principal component analysis (PCA) model: (i) freeze-dried cake strength and bulk fill-related properties, (ii) compression behaviour-related properties, and (iii) flow-related properties. These properties were influenced by the HPMC viscosity grade, HPMC proportion and size fraction of excipient used. Freeze-dried excipients containing vLV or lower HPMC proportions had higher bulk densities, thus displaying better packing within the die. For larger excipients, densification by plastic deformation was likely preceded by fragmentation, thus accounting for the higher yield pressure values. The establishment of inter-variable relationships between the physical properties would be useful in further studies on the functional properties of tablets containing these co-freeze-dried mannitol-HPMC tableting excipients.