Assessment of the plasticity of dry granulated particles (mini-tablets) and its relationship to their tabletability

Abstract

Mini-tablets of different proportions of α-lactose monohydrate (LAC) and microcrystalline cellulose (MCC) were prepared by uniaxial compaction and served as surrogate granules. The inverted Adams coefficient i.e., α ^-1 was derived from bulk mini-tablet compression data and used as an indication of granule plastic deformation. The correlation of the parameter to single granule deformability assessed from uniaxial single mini-tablet compression and macro-indentation hardness was investigated. Furthermore, the relationship between the plastic deformation parameters and the tabletability of mini-tablets were evaluated. An increased MCC concentration resulted in an increased indentation hardness and deformability of the mini-tablets, but no correlation was found between indentation hardness and the α ^-1 coefficient. Thus, the plastic deformation expressed during powder compression showed no relationship to the single specimen indentation hardness and plastic deformability. An increased indentation hardness tended to correspond to an increased tablet tensile strength, while the opposite applied for the α ^-1 coefficient. The trend of increased tablet tensile strength with higher MCC concentration was broken at the highest MCC concentration, i.e., for mini-tablets showing very limited fragmentation. It was concluded that granule plastic deformation is a key property for granule tabletability. It is suggested that granule plastic deformation should be assessed during granule engineering.

Keywords: Compression parameters; Dry granulation; Fracture force; Indentation hardness; Mini-tablets; Powder compression; Tablet tensile strength.

Graphical abstract

Fig. 1

The a) indentation test tablet porosity as a function of the intra-granular porosity and b) indentation hardness as a function of the axial single mini-tablet plastic deformation for all compositions, compacted at 50 (red dots) and 100 MPa (gray squares). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Examples of dents after indentation of indentation test tablets of a) 100% f_MCC and b) 0% f_MCC compacted at 100 MPa.

Fig. 3

Typical Adams plots for all mini-tablet compositions compacted at 50 and 100 MPa. The dotted lines show the pressure region used in the linear regressions.

Fig. 4

Typical engineering-strain (C) – pressure (P) profiles for two types of granules composed of 100% f_MCC (left), 50% f_MCC (middle) and 0% f_MCC (right). The solid lines denote the mini-tablets used in this study prepared at 50 MPa and the dashed lines denote dry granulated particles with a size fraction 500–710 μm reported earlier (Tofiq et al., 2022b).

Fig. 5

The inverted Adams coefficient for the mini-tablets) (${\alpha }_{\mathrm{mt}}^{-1}$) as function of the inverted Adams coefficient for dry granulated particles prepared by slugging (${\alpha }_{\mathrm{g}}^{-1}$, (Tofiq et al., 2022b).

Fig. 6

The tablet tensile strength (σ_t) as a function of the a-b) tablet porosity (E_t) and c-d) tableting pressure (P) for all mini-tablet compositions compacted at 50 and 100 MPa. The bars denote the standard deviations.

Fig. 7

The inverted Adams coefficient α⁻¹ as a function of the indentation hardness (HB) for all compositions compacted at 50 and 100 MPa.

Fig. 8

The Adams α⁻¹ coefficient as a function of the Heckel yield pressure P_y (Tofiq et al., 2022b) for all compositions compacted at 50 (red dots) and 100 MPa (gray squares). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 9

The tablet tensile strength at compaction pressure 300 MPa as a function of a) indentation hardness (HB) and b) inverted Adams coefficient α⁻¹ for compositions prepared at 50 (red dots) and 100 MPa (gray squares). In b) data for dry granulated particles of a size fraction 500–710 μm (Tofiq et al., 2022b) are added for comparison (dashed lines). The bars denote the standard deviations. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)