Roller Compaction of Anhydrous Lactose and Blends of Anydrous Lactose with MCC

The authors studied the behavior of anhydrous lactose and the combination of anhydrous lactose and the combination of anhydrous lactose with microcrystalline cellulose on a pilot-scale roller compactor.
Apr 01, 2009

Roller compaction is method of preparing granules for capsules or for tablet formulations. The most common filler–binder excipients used in roller compaction are microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP), and lactose. Studies on the dry granulation of various types of lactose have shown anhydrous lactose to be the best lactose for roller compaction because its brittle nature leads to excellent recompaction properties (1).

Figure 1: Schematic of the Chilsonator roller compaction process. HFS is horizontal feed screw; VPS is vertical precompression screw.(all figures are courtesy of the authors.)
Figure 1 is a schematic of the roller compaction process, including the feed hopper from which the formulation mix is fed by the horizontal feed screw (HFS) to the vertical precompression screw (VPS). The VPS deaerates the powder and increases the density of the powder to approximately its tapped bulk density (TBD) just before it is compacted between the two counterrotating rolls. Beneath the rolls the resulting ribbon is milled by the in-line mill to produce the final granulate product.

The authors investigated the stability of the roller compaction process and the resulting tableting properties of the granules formulated with anhydrous lactose and with combinations of anhydrous lactose and MCC.

Materials and methods

The materials consisted of the following: anhydrous lactose (SuperTab 21AN, DMV-Fonterra Excipients, Nörten-Hardenberg, Germany), MCC (Pharmacel 102, DMV-Fonterra Excipients), and magnesium stearate (BUFA, Uitgeest, The Netherlands).

FIigure 2: The Chilsonator IR520 pilot-scale roller compactor (The Fitzpatrick Company Europe).
Roller compaction. Roller compaction was performed with an IR520 Chilsonator machine (The Fitzpatrick Company Europe, see Figure 2) with knurled bevelled rolls fed by a horizontal and a vertical feed screw rotating at ~12 and 200 rpm, respectively. The rolls rotated at the minimum speed of 6 rpm (range 6–22 rpm). The minimum speed was used to best monitor the compaction process. The temperature of the ribbons was measured with an infrared thermometer. Subsequent, in-line milling was performed with the FitzMill model D6A system (The Fitzpatrick Company) that incorporated a knife forward rotor set at a speed of 800 rpm with 1-mm screens (#1532-0040). The time needed to process a certain mass of powder was measured to calculate the throughput of each powder blend at a roll line force of 4.2 kN/cm.

Particle-size distribution. The particle-size distribution (PSD) of the granules was determined with laser diffraction using a Helos system (Sympatec, Clausthal-Zellerfeld, Germany).

Poured and tapped bulk density. Granule poured and tapped bulk densities were determined using ~230 mL of powder in a 250-mL graduated cylinder. Volume and mass were measured before and after 1250 taps.

Tablet compaction. Granule and powder blends were compacted with a rotary press (Rotab-T, Luxner, Berlin, Germany) equipped with 9-mm flat beveled punches. Tablets weighing 250 mg were produced in all cases.

Tablet-crushing strength. The tablet-crushing strength was tested on 10 tablets the day following compaction.

Tablet friability. Friability was tested in accordance with US Pharmacopeia ‹1210 ›.

Tablet weight uniformity. The relative standard deviation (RSD) of the weight of 10 tablets was calculated.

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