(233r) Behaviour of Magnesium Stearate in Continuous Feeding

Behaviour of magnesium stearate in
continuous feeding

Raghu V. G. Peddapatla*^1,2,
Caroline A. Blackshields^1,2, Michael F. Cronin¹, Abina M.
Crean^{1,2, 3}

¹School of Pharmacy, University College Cork, Ireland

²Pharmaceutical Manufacturing Technology Centre, Ireland

³Synthesis and Solid State Pharmaceutical Centre, Ireland

*School of Pharmacy,
University College Cork, Ireland, Tel: + 353 (21) 4901683,

email: r.peddapatla@umail.ucc.ie

INTRODUCTION

In a pharmaceutical continuous process line,
feeding powders constantly and accurately into downstream processing units is
challenging ¹. Consistent feeding is
particularly challenging for cohesive materials such as the powder lubricant, magnesium
stearate (MgSt). Even small changes in the feedrate of powders being fed for a
short period of time, could result in products falling off the specification
limits². Hence, the initial
feeding raw material step is important and must be monitored continuously to
achieve consistency in feeding. Feeding of pharmaceutical excipients into continuous
process lines is most commonly accomplished through Loss-In-Weight (LIW) or
Loss-In-Volume (LIV) feeders which operate in gravimetric or volumetric mode ^1,3.

In this study the continuous feeding of magnesium
stearate alone and as a component of a tablet blend was studied. Magnesium
stearate was selected as it is the most commonly used powder lubricant in tablet
processing, and variability in its properties can comprise tablet ejection
compaction, and performance (hardness and dissolution)⁴ .

The objectives of this study were

1. To identify
how the physical attributes of four different grades of magnesium stearate affect
its continuous feeding performance.

2. To identify
the effect of continuous feeding rate on the compaction and properties tablets
prepared from blends (with and without lubricant).

MATERIALS

Four different grades of magnesium stearate
obtained from two different suppliers, hereafter referred to as samples 1-4.

METHODS

Magnesium Stearate characterisation

Physical properties such as powder flow, bulk
density, % compressibility are analysed using Brookfield powder flow tester
(PFT) and Laser Light Scattering (Malvern 3000) for particle size distribution

Blends Preparation

Two blends are prepared in double cone Erweka blender
blended for 30 minutes @ 30 rpm. Magnesium stearate is added to one of the
blend and blended for extra 1minute @ 30rpm Blend 1 composed of 90% microcrystalline
cellulose PH200 and 10% metoclopramide HCl. Blend 2 composed of 89.5% microcrystalline
cellulose PH200 and 10% metoclopramide HCl and 0.5% magnesium stearate.

Feeder setup and evaluation

Loss in weight feeder are designed to monitor the
changes in the bulk density of the powder in the feeder hopper⁵. Powders are fed through
a K-Tron MT12 feeder using self-cleaning screws with fine square screen in
gravimetric mode.  Magnesium stearate samples are fed using Coarse Concave
Screws (CCS) with Fine Square Screen (FSqS) setup, with two different set
points of 0.15kg/hr. and 0.25kg/hr. Both blends are fed at 3 different set
points 0.2238kg/hr., 0.5594kg/hr. and 1.0069kg/hr. with Fine Concave Screw
(FCS) & Fine Square Screen (FSqS).

Mass flow performance was measured independently
using a K-Sample Test System for Gravimetric Feeders. The relative standard
deviation (RSD %) was determined from data collected at 30 sec intervals over a
30 minute duration.

RESULTS AND DISCUSSION

Continuous feeding performance

Feed factor is the gravimetric speed equivalent for
100% screw speed with a specific screw and screen setting. It gives an
indication of the max. feed rates that can be achieved for a powder with
specific equipment set up.  Table 1 shows the measured bulk density and feed
factors for the 4 grades of magnesium stearate studied.

Table 1

Physical properties of magnesium stearate impact on
gravimetric powder feeding behaviour. Samples feed factors are directly
proportional to their bulk densities.

A measure of feed performance is the variability in quantity
feed which is expressed as the relative standard deviation (RSD %). In this
study weights where determined at 30 sec intervals for a duration of 30
minutes. The results for magnesium stearate alone and tablet blends are shown
in Figure 1.

Figure 1: Feeding performance of magnesium
stearate samples (left) and blends (right)

Magnesium stearate samples showed less variability at higher
set points and greater variability at lower set points (Figure 1 left). Brookfield
powder flow testing results showed magnesium stearate samples to exhibit very
cohesive to cohesive flow behaviour and no relationship was seen between the
feed variability and the measured flow function coefficient.

Blend 2 (which contained magnesium stearate) showed a lower %
RSD compared to blend 1 at 3 different set points (Figure 1 right). Two blends
fed at the lowest fed rate, 0.2238kg/hr, showed the highest variability.  

Figure 2: Tensile Strength profiles of both blends
fed through the feeder at a range of fed rate set points. 

There was no significant difference observed in tensile
strength profiles fed at different set points for control blend 1, without
magnesium stearate. Whereas the blend 2, with magnesium stearate, showed
decrease in tablet tensile strength profiles upon feeding at higher set points
(Figure 2). This may be due to increased mixing between the screws, as screws
rotate with greater speeds upon increase in set point and would increase
blending of the blend.

CONCLUSIONS

The bulk density magnesium stearate effected its feed
factor - the higher the bulk density, the higher the feed factor achieved. While
all magnesium stearate samples showed higher feeding variability at a lower
feed rate, the difference was more pronounced for magnesium stearate samples 1
and 4. The physical properties responsible for differences in magnesium
stearate feeding performance are currently being investigated.

The feeding rate of the blend containing
magnesium stearate was seen to undermine its compaction properties. The higher
the feeding rate the lower the tensile strength of the tablet produced.  Future
work will look at feeding rate impact on tablet dissolution.

ACKNOWLEDGEMENTS

Research funded by Pharmaceutical
Manufacturing Technology Centre (PMTC), an Enterprise Ireland, Irish
Development Agency funded centre and Synthesis and Solid State Pharmaceutical Centre (SSPC)
and Science Foundation Ireland (SFI) under grant number 12/RC/2275. PH200 was
donated by FMC Corporation. K-Tron for support in use of MT12 micro feeder.

BIBLIOGRAPHY

1.        Engisch WE, Muzzio FJ. Method for
characterization of loss-in-weight feeder equipment. Powder Technol. 2012;228:395-403.
doi:10.1016/j.powtec.2012.05.058.

2.
       Pernenkil L, Cooney CL. A review on the continuous blending of powders. Chem
Eng Sci. 2006;61(2):720-742. doi:10.1016/j.ces.2005.06.016.

3.
       Simonaho S, Ketolainen J, Ervasti T, Toiviainen M, Korhonen O. European
Journal of Pharmaceutical Sciences Continuous manufacturing of tablets with
PROMIS-line — Introduction and case studies from continuous feeding , blending
and tableting. PHASCI. 2016. doi:10.1016/j.ejps.2016.02.006.

4.
       Gupta A, Hamad ML, Tawakkul M, Sayeed V a, Khan M a. Difference in the
lubrication efficiency of bovine and vegetable-derived magnesium stearate
during tabletting. AAPS PharmSciTech. 2009;10(2):500-504.
doi:10.1208/s12249-009-9229-y.

5.
       Engisch WE, Muzzio FJ. Feedrate deviations caused by hopper re fi ll of
loss-in-weight feeders. Powder Technol. 2015;283:389-400.
doi:10.1016/j.powtec.2015.06.001.