Friday, 26 November 2021 21:51

Effect of binder type and lubrication method on the binder efficacy for direct compression

Written by Cedrine de Backere, Valérie Vanhoorne, Chris Vervaet
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The development of direct compression (DC) formulations can remain challenging as certain active pharmaceutical ingredients show poor compactibility. Therefore, a binder can be added to the formulation to increase tablet strength, reduce tablet friability and/or prevent tablet defects such as chipping, capping and lamination. While different studies have investigated the effect of binders in formulations for roller compaction (1) and wet granulation (2,3), less studies focused on dry binder addition and binder efficacy in DC formulations. In this study, the effect of ten binders included in different concentrations on DC formulations was investigated. Three fillers with different deformation mechanisms were selected and combined with these binders. Furthermore, two lubrication methods, internal and external lubrication, were applied on all formulations to study the lubricant sensitivity (i.e. reduction of tensile strength due to the internal blending of magnesium stearate). This study aims to facilitate binder selection for direct compression formulations by highlighting the impact of a wide variety of binders and their underlying material properties on tablet critical quality attributes (tensile strength, disintegration) and in-process controls (ejection force).

Materials and methods

Ten different binders were investigated: HPC (Klucel® EF and EXF) povidone (Kollidon® K30), copovidone (Kollidon® VA64 and VA64F), MCC (Avicel® PH105 and PH200), HPMC (Methocel® E15), native maize starch and partially pregelatinized maize starch (Starch 1500®). Binder characteristics were determined to quantify particle size, density, compaction properties and wetting behaviour. The binders were combined in concentrations of 10, 20 and 30% (w/w) with each filler (DCP, lactose and MCC PH102). Two lubrication methods were applied: internal (0.75% w/w magnesium stearate) and external lubrication. Tablets were produced using a STYL’One Evolution compaction simulator (Medelpharm) equipped with an external lubrication system. The evaluated responses were ejection force, tensile strength and disintegration time.


Results and discussion

Ejection forces:

The addition of a binder caused a reduction of the ejection forces compared to tablets composed of pure filler. Moreover, ejection forces were further lowered, up to 50% using a higher binder concentration. Comparable ejection forces were recorded for both lubrication methods.


Tensile strength:

As the tensile strength of pure DCP tablets was independent of the lubrication method, binder formulations with DCP as filler were used to study the binder lubricant sensitivity. All binders showed lubricant sensitivity to some extent. The highest lubricant sensitivity was observed for E15, especially at higher binder levels. However, the effect of binder concentration on lubricant sensitivity was less pronounced for the HPC grades, due to lower plasticity of KEF and KEXF. Plasticity levels were 75% and 72% for KEF and KEXF, respectively, while other binders showed a plastic value above 88%.


In general, the highest tensile strength was observed for VA64F and PH105 as binders. In contrast, E15 and S1500 yielded tablets with the lowest tensile strength, for all filler combinations and both lubrication methods. Tensile strength of those binders was lower compared to tablets of pure filler for all binder levels. Intermediate binder efficacy was observed for the other binders (VA64, K30, PH200 and NMSt) as these binders only moderately affected the tensile strength compared to binders showing high (VA64F and PH105) and poor (E15 and S1500) binder efficacy.

As the binders showed different effectiveness in terms of tensile strength, it was of interest to study the underlying effect of binder properties on tensile strength by means of a PLS (partial least squares) model. Analysis of the loading scatter plot (Figure 1b) revealed a positive correlation between tensile strength and cohesion index and specific work of compaction was found. In contrast, particle size, elasticity, and tablet brittleness index (to a lesser extent) were negatively influencing the tensile strength. Hence, binders with high plasticity (high specific work of compaction), high cohesion index and small particle size generally yielded tablets with high tensile strength.


Three main clusters could be distinguished in the PC1 vs PC2 score scatter plot (Figure 1a):

  1. KEF and KEXF clustering in the left top corner of the scatter plot (green). These binders possessed high values for wall friction angle and elasticity, and low values for SpecWorkComp. As a result, low tensile strength (i.e. poor binder efficacy) was observed for those binders.
  2. In the center of the plot, a cluster was formed by E15, NMSt, VA64, S1500, K30, PH200 (red) showing intermediate values for most powder properties. E15 and S1500 exhibited the most negative scores along PC1 within this cluster, linked to high elasticity levels, which is in accordance with their poor binder efficacy.
  3. PH105 and VA64F were located on the right side of the score scatter plot (blue). These binders possessed high values for cohesion index and specific work of compaction and in addition, small particle size, low elasticity and low tablet brittleness. As a result, the highest tensile strength was observed for tablets formulated with PH105 and VA64F as binders.


Figure 1: PC 1 versus PC2 score scatter plot (a) and loading scatter plot (b) of the tensile strength model. Binder clusters are visualised in different colours.

While both HPC grades, KEF and KEXF, clustered in the score scatter plot due to predominantly high values for WFA and elasticity, other grades of the same compound (VA64 and VA64F, PH200 and PH105) were located in different clusters (Figure 1a) indicating the importance of particle size of different grades towards binder efficacy.


Disintegration time:

Internal lubrication generally prolonged the disintegration time compared to external lubrication. Wettability measurements, via determination of contact angle, correlated well with the disintegration behaviour of the binders (Figure 2). MCC (PH105 and PH200) and starch (S1500 and NMSt) grades were characterized by good wetting properties (i.e. low contact angle values), resulting in a fast disintegration. In addition, the higher water binding capacity of the MCC and starch grades can be associated with faster tablet disintegration. Poor wetting (i.e. high contact angle values) was observed for KEF, KEXF and E15, contributing to the delayed or even lack of disintegration of these binders.

Although, for the different grades of the same compound (VA64 and VA64F, PH200 and PH105) a smaller particle size resulted in faster disintegration, still different grades of the same compound were located in the same cluster illustrated in Figure 2, indicating a predominant effect of binder type on disintegration.

Figure 2: Contact angle (CA) of the pure binder tablets measured immediately after a drop of demineralized water touched the tablet surface (CA_t0) and after 30 s (CA_t30).



Overall, VA64F and PH105 resulted in the highest tensile strength, whereas poor binder efficacy (i.e. low tensile strength) was observed for E15 and S1500. Compaction properties and particle size were found the most predominant factors for the tensile strength. The effective binder concentration was depending on filler, binder type and lubrication method. Lubrication method influenced the tensile strength as lubricant sensitivity was observed for all binders. Disintegration was dominated by binder type and filler, but less by the lubrication method. Fast disintegration was observed for the MCC (PH105 and PH200) and starch (S1500 and NMSt) grades, whereas both HPC (KEXF and KEF) grades and E15 resulted in delayed disintegration. Wettability measurements correlated well with the disintegration behaviour of the binders and can therefore be used as an indicative measurement.


Full version

The full version of this article can be consulted at:



This research was financially supported by the FWO Flanders (grant: 1S88518N). The authors acknowledge JRS Pharma, DFE Pharma and Roquette Frères for providing samples.



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