The effect of excipient particle size on the reduction of compactibility after roller compaction

Abstract

Developing a robust roller compaction process can be challenging, due to the diversity in process parameters and material properties of the components in a formulation. A major challenge in dry granulation is the reduction of tablet strength as a result of re-compaction of the materials. The aim of this study is to investigate the impact of excipient type and particle size distribution on tablet tensile strength after roller compaction. Lactose monohydrate, anhydrous lactose and microcrystalline cellulose with different particle sizes are roller compacted at varying specific compaction forces. Granules obtained are compressed into tablets to evaluate the reduction in tablet strength upon increasing the specific compaction force. The impact of particle size of the starting material is shown to be vastly different for the three types of excipients investigated, due to the differences in mechanical deformation mechanisms. The presence of rough surfaces and a high degree of fragmentation for anhydrous lactose appears to be beneficial for compaction and re-compaction process. Additionally, the particle size of anhydrous lactose hardly affects the tensile strength of tablets, which can be beneficial for the robustness of a roller compaction process.

Keywords: Dry granulation; Excipient(s); Formulation composition; Material science; Particle size; Roller compaction.

Graphical abstract

Fig. 1

SEM pictures of milled lactose monohydrate Pharmatose 200 M (as used in formulation LM2, left), anhydrous lactose SuperTab 21AN (as used in formulation AL2, middle), and microcrystalline cellulose Pharmacel 102 (as used in formulation MCC2, right).

Fig. 2

Tablet tensile strength of granules from the three milled lactose monohydrate grades (A-C), three anhydrous lactose grades (D-F) and two microcrystalline cellulose grades (G-I) after roller compaction at different specific compaction forces. Tablet compression is performed at 5 kN (left), 10 kN (middle) and 15 kN (right). N = 20 tablets per datapoint were analyzed and error bars represent the standard deviation. Solid lines represent linear fits (A-F) and exponential fits (G-I) to quantify the decrease in tablet tensile strength upon increasing the specific compaction force.

Fig. 3

Relationship between relative bulk density and tablet tensile strength for the roller compacted granules of lactose monohydrate (red), anhydrous lactose (blue) and microcrystalline cellulose (purple).Tablet compression is performed at 5 kN (left), 10 kN (middle) and 15 kN (right). N = 2 repeats for density measurements and N = 20 tablets per datapoint were analyzed. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)