How to minimize the limitations of roll compaction - Pharmaceutical Technology

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How to minimize the limitations of roll compaction
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 — was examined. Despite some disadvantages, such as the loss of reworkability of roll compacted substances, the authors confirmed the feasibility and benefits of roll compaction for each case.


Pharmaceutical Technology Europe
Volume 21, Issue 12


(Brad Goodell/Getty Images)
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

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

Methods

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.


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