Atypical compaction behaviour of disordered lactose explained by a shift in type of compact fracture pattern

Abstract

The objective was to investigate tabletability and compactibility for compacts of a series of α-lactose monohydrate powders with different degree of disorder. Regarding the tabletability, the powders of high degree of disorder displayed similar behaviour that deviated markedly from the behaviour of the crystalline powders and the milled powder of modest degree of disorder. The Ryshkewitch-Duckworth equation, describing compactibility, was nearly linear for the crystalline powders, while for the disordered powders the model failed to describe the relationships, i.e. the disordered powders were characterised by a plateau in the Ryshkewitch-Duckworth plots over a relatively wide range of compact porosities. It was concluded that the difference in compaction behaviour of the milled particles compared to the crystalline powders was primarily explained by the increased particle plasticity of the disordered particles. The plateau in the Ryshkewitch-Duckworth plots obtained for the disordered powders was explained by a change in the fracture behaviour of the compacts, from an around grain to an across grain fracture pattern. This implied that the disordered particles can be described as a type of core-shell particles with an amorphous shell and a defective crystalline core.

Keywords: Compaction pressure; Core-shell particles; Lactose; Porosity; Tablet fracture; Tensile strength.

Graphical abstract

Fig. 1

The tensile strength (σ_t) and compaction pressure (P) relationship of crystalline lactose CL200, crystalline lactose LH300, lactose milled for 60 min (ML60), lactose milled for 300 min (ML300), lactose milled for 1200 min (ML1200) and spray-dried lactose (SDL). Powder was pre-stored at 0% RH.(A) and 33% RH (B) prior compaction. The dashed horizontal line represents the maximum tensile strength (σ_{t, max}) and the dashed vertical line represents the pressure at which the σ_{t, max} is reached. The error bars represent the standard deviations.

Fig. 2

(A) the maximum tensile strength (σ_{t, max}), (B) the slope of compact tensile strength and compaction pressure relationship profile (k_c) and (C) the second threshold pressure (P_c2) as function of degree of disorder. Powder was pre-stored at 0% RH (blue symbol and blue solid line) and at 33% RH (red symbol and red dashed line) prior compaction. The error bars represent 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.)

Fig. 3

The tensile strength (σ_t) and porosity relationship of crystalline lactose CL200, crystalline lactose LH300, lactose milled for 60 min (ML60), lactose milled for 300 min (ML300), lactose milled for 1200 min (ML1200) and spray-dried lactose (SDL) using Ryshkewitch-Duckworth model. Powder was pre-stored at 0% RH (A) and 33% RH (B) prior compaction. The red dashed horizontal line represents the maximum tensile strength (σ_{t, max}) and the red dashed vertical line represents the porosity at the σ_{t, max}. The error bars represent 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.)

Fig. 4

SEM images of outer surface and fracture surface of compact fragments of spray-dried lactose. The powder was compacted at 50, 100, 200 and 300 MPa corresponding to a porosity of 0.25, 0.18, 0.04 and 0.03, respectively.