How to minimize the limitations of roll compaction

December 1, 2009

Pharmaceutical Technology Europe

Pharmaceutical Technology Europe, Pharmaceutical Technology Europe-12-01-2009, Volume 21, Issue 12

The application of roll compaction as a dry granulation method for three different drug types — herbal dry extract, poorly compactable drug and a sustained-release matrix tablet &#amp;151; was examined.

There are two dry granulation methods in the pharma industry: slugging and roll compaction. During the 1950s–1970s, dry granulation was mainly performed by slugging; however, nowadays, roll compaction is the preferred method because it offers greater production capacity, and simplified and continuous processing.1

(Brad Goodell/Getty Images)

In roll compaction, powder blend is compacted into dense ribbons between two counter-rotating rolls without the use of a liquid binder. The produced compacts are then broken into granules by milling and can be subsequently compacted into tablets or filled into capsules. Compared with wet granulation, the process is continuous and simple, and is especially useful for moisture and/or heat sensitive materials because liquids and a drying step are not required.2

Because of these advantages, roll compaction is being increasingly used as a granulation technique, but it is not a simple process; many variables are involved including roll pressure, roll speed and horizontal/vertical feed screw speed. These parameters need to be optimized depending on the materials and the type of equipment used in order to obtain products of desirable quality. In particular, the commonly reported 'loss of reworkability' phenomenon, which has been confirmed by many authors3–5 and can lead tablets to show inferior strength compared with direct-compacted tablets, should be considered to achieve a successful formulation.

This article provides a brief overview of roll compaction and some useful suggestions to minimize the technique's limitations. Three different applications for roll compaction were chosen for the study: herbal dry extract compaction and tabletting; poorly compactable drug compaction; and the formulation of sustainedrelease matrix tablets. The influence of roll compaction was investigated using an experimental design and the results suggest that roll compaction is a powerful technique for each of the investigated cases.

Roll compaction and tabletting of herbal dry extract


The granulation and tabletting of Hypericum perforatum (also known as St. John's Wort) dry extractcontaining powder mixture were performed using roll compaction. Hypericum perforatum possesses good efficacy against mild to moderate depression with relatively few side effects and the importance of this plant as an alternative antidepressant is continuously growing.6,7 However, as with many other herbal dry extracts, Hypericum perforatum dry extract does not exhibit favourable physical properties for direct compaction, such as acceptable flowability and compressibility. Therefore, granulation prior to tabletting is strongly recommended.

Following on from earlier studies,8,9 the present study aimed to investigate and supplement the effect of roll compaction on the granule and tablet properties of Hypericum perforatum dry extract, which has not been investigated in previous studies. Furthermore, the influence of two critical roll compaction variables — roll pressure and roll speed — were examined and optimized using a central composite design.

The powder mixture comprised 20% (w/w) Hypericum perforatum dry extract, 70.5% microcrystalline cellulose (Avicel PH 101; FMC Biopolymer, Belgium), 7% corn starch (Melon, France), 2% soy polysaccharides (Emcosoy; JRS Pharma GmbH, Germany) and 0.5% hydrogenated vegetable oil/hydrogenated oil (Lubritab; JRS Pharma GmbH, Germany).

Powder blend was roll compacted by a roll compactor (Chilsonator IR 220; Fitzpatrick, Belgium) equipped with smooth rim rolls. A twofactor, twolevel central composite design (a progression from factorial design that provides a powerful tool for optimization) was employed to identify optimal process conditions. Roll pressure and roll speed were chosen as independent variables and each variable had two levels coded as 1 and 1, respectively. The number of centre point in cube (0, 0) and α value were customized as 1. A total number of nine experiments comprising four axial points, four cube points and one centre point in cube were conducted and the centre point was replicated.

The statistical analysis of data and optimization was performed using Minitab software (Minitab Inc., USA). The effects and interactions of variables were calculated and their significances were evaluated at the confidence levels of 90%, 95% and 99%.

After roll compaction, the produced ribbons were broken into granules using a Fitzmill (Fitzpatrick, Belgium) and tabletting was conducted using a Zwick 1478 universal material tester (Zwick GmbH, Germany). Flatfaced tablets of 8 mm diameter and 300 mg of mass were compacted with non-granulated and granulated blend at a compaction force of 25 kN. The tabletting speed was set to 200 mm/min. Hausner ratio and Carr's index were used as the indicator of flowability, and particle size was measured using laser diffraction (Mastersizer X; Malvern Instruments, UK).

For describing size distribution, span and uniformity were taken; the smaller the span and uniformity values, the narrower the distribution.


Following roll compaction, particle size and flowability increased; however, tablet hardness decreased significantly (Table 1). This is because of loss of reworkability, caused by double compaction during roll compaction and subsequent tabletting, as also reported in previous works.3–5 This phenomenon can be explained by crystal lattice structure. In crystal lattice, plastic flow takes place by pressure in the direction to fill the blank spaces. As this plastic deformation is irreversible, if the blank spaces already become partially occupied by roll compaction, less plastic flow is available for further plastic deformation during subsequent tabletting.

Despite this, the use of roll compaction as a granulation method for Hypericum perforatum dry extract was successful. The disintegration time of the tablets made using roll compacted granules was considerably shorter than that of directcompacted granules (Table 1), which can be explained by the facilitation of water penetration into the tablet caused by a more porous structure after roll compaction.

Table 1: Granule and tablet properties made of Hypericum perforatum dry extract before/after roll compaction.

Following on from this success, roll compaction could also be used as a novel choice for other herbal dry extracts to improve the impact of their undesirable properties on formulation processes.

Roll compaction and tabletting of a poorly compactable drug

Paracetamol is a known poorly compactable drug. Because of its unfavourable properties for direct compaction, paracetamol tablets are almost exclusively produced by wet granulation.10 In this study, roll compaction was utilized as a granulation method and its effects were studied. The composition used was paracetamol (60% w/w), microcrystalline cellulose (37.5%), croscarmellose sodium (2%) and magnesium stearate (0.5%).

Table 2: Granule and tablet properties made of paracetamol-containing mixture before/after roll compaction.

As presented in Table 2, roll compacted granules showed considerably improved flowability compared with the starting powder blend, as well as reduced disintegration time. Although tablet tensile strength did decrease after roll compaction, it was still within an acceptable range for further formulation processing, such as coating. Roll compacted granules showed greater mean yield pressure in Heckel plot compared with the starting powder, which indicated inferior plasticity (Figure 1). No considerable difference was observed in drug release pattern before/after roll compaction. Therefore, it could be possible to modify only physical properties, such as flowability using roll compaction without affecting drug release behaviour.

Figure 1

Roll compaction and formulation of matrix tablets

Hydroxylpropyl cellulose (HPC)based sustainedrelease matrix tablets were prepared via roll compaction. The feasibility and the effect of roll compaction were evaluated and a comparative study with direct compaction was conducted.

Firstly, HPC grade and granule size were optimized to achieve the best granule flowability and 8–12 h of sustained-release of caffeine, which was employed as a model drug. This goal could be achieved using low-substituted HPC and a granule size of 500–710 µm. As the next step, roll pressure and milling speed were optimized to maximize the yield of desired size fraction (500–710 µm). Using roll pressure of 10 bar and milling speed of 488 rpm, the best yield of desired granule size fraction was obtained. The matrix tablets prepared via optimized roll compaction process were then compared with the directcompacted matrix tablets.

The tablets produced via roll compaction exhibited inferior tensile strength and a more distinguishable swelling behaviour than directcompacted tablets. Regarding drug release profile, it was revealed that diffusion was the predominant release mechanism in all cases. Despite this, the tablets produced via roll compaction showed a faster drug release compared with directcompacted tablets, and the aimed sustained-release of caffeine (8–12 h) could be achieved (Figure 2) with the better weight uniformity of tablets by roll compaction. From the results, it was concluded that roll compaction is a suitable granulation method for the preparation of HPCbased matrix tablets.

Figure 2


The results have shown that roll compaction could successfully improve important physical properties, such as flowability and granule size distribution, of the starting material; however the tensile strength of the final tablet will be reduced. Therefore, dry granulation by roll compaction can be a good choice for other substances that have similar properties to the investigated materials in the present research, and its application could be broadened.

Related studies on other excipients for roll compaction, and the effect of the tabletting condition of roll compacted granules would be very useful to adjust the desired properties of granules and tablets in formulation procedures.

Imjak Jeon is Postdoctoral fellow at the Industrial Pharmacy Lab, Department of Pharmaceutical Sciences, University of Basel, Switzerland.Tel. +41 (0)61 381 0723

Bikrom Maurya is a student at the Indian Institute of Technology-Guwahati, 781039 Guwahati, India.

Tiziana Gilli is a student at the Department of Pharmaceutical Sciences, University of Basel, Switzerland.

Thierry F. Vandamme is Professor of the Faculty of Pharmacy, Laboratory of Conception and Application of Bioactive Molecules, University of Strasbourg, France.

Gabriele Betz is Head of Industrial Pharmacy Lab, Industrial Pharmacy Lab, Department of Pharmaceutical Sciences, University of Basel, Switzerland.


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9. S.G. Von EggelkrautGottanka et al., Pharm. Dev. Technol., 7(4), 447-455, (2002).

10. T. Martinello et al., Int. J. Pharm., 322(1–2), 87–95 (2006).


The authors are grateful to the University of Strasbourg (France) for providing the Hypericum perforatum dry extract and to Fitzpatrick Company (Belgium) for the kind offer of their equipment.