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Jason Dawes1, John F. Gamble2, Mike Tobyn2, Phillip Robbins1, Richard Greenwood1
1School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT 2Materials Science, DPST, Bristol-Myers Squibb R&D, Moreton, Merseyside, CH46 1QW, UK
1. IntroductionThe deleterious effects of magnesium stearate on the properties of roller compacted ribbons and hence tablets are well documented [1]. The extent of these effects can be
limited through the implementation of a two-step mixing operation [2], in which a formulation is blended to homogeneity prior to the addition of magnesium stearate. The
secondary mixing step including magnesium stearate is limited, such that it is non-homogenously distributed within the formulation. Consequently the formulation is sensitive to
further mixing that can occur during further downstream processes [3], such as within the feeding system of a roller compactor. The influence of mixing within the feed system is
likely to alter the „lubricity‟ of the formulation and hence have an unpredictable affect on the tablet properties.
The aim of the current study is to characterise the role of magnesium stearate during roller compaction and hence to determine the actual need
for its inclusion.
3. MethodsFormulation: Avicel Ph102, lactose anhydrous, croscarmellose sodium, magnesiumstearate
Mixing: Step 1 – formulation tumble blended for 10 minutes (15 rpm) (withoutmagnesium stearate), Step 2 – Further blended with magnesium stearate for either 7minutes (15 rpm) or 60 minutes (15 rpm)
Lubricant sensitivity – tensile strength of
tablets compacted from just mixed formulation (7
minutes mixing) was compared to the tensile
strength of formulation which had transitioned
through the roller compactor feeding system
Roller compaction – the initial experiment was
designed to produce unlubricated ribbons of
varying porosity by altering the process
parameters. This was achieved by finding the
minimum pressure required to maintain a roll gap
of 2.2 mm at a range of screw speed. Roll speed
was kept constant at 3.4 rpm. The process
parameters were repeated for lubricated ribbons
2. Roller Compactor Particle size enlargement step
Powder force fed via the action of ascrew feeder
Compaction zone split into threeregions
Slip region – low pressure,densification largely due toparticle rearrangement
Nip region – powder „grips at theroll surface, high pressure, ribboncompact formed
Release region – ribbon releasefrom roller surface, elasticrecovery
Formulation sticking to roll surface is acommon problem [4]
Pressure transducers located acrossroll width measure pressure profiles
Uneven pressure distribution [5]
Po
Nip
Angle
Release
AngleFormulation on rolls
Higher density at centre
Auger Speed
(rpm)
Hydraulic
Pressure (bar)
25 45
30 60
32 80
34 110
7. Conclusion
Use of a two step mixing operation, in which magnesium stearate is non-
homogenously distributed throughout a blend renders the formulation sensitive to any
further uncontrolled mixing within the feeding system of a roller compactor
Addition of magnesium stearate to a placebo formulation prior to roller compaction
has an unexpected advantage of improving mass throughput and increasing nip
angle, possibly due to the densification kinetics in the slip region
This increase in mass throughput with increasing magnesium stearate plateaus
above 0.25% w/w, additional magnesium stearate provides no further benefits
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
0 20 40 60 80 100
Bu
lk D
en
sit
y (
g/c
m3)
Normal Pressure (MPa)
0.01% (w/w)
0.1% (w/w)
0.25% (w/w)
0.5% (w/w)
1.0% (w/w)
6. Instrumented Rollers
The nip angle was found to increase with increasing magnesium stearate at low levels
(< 0.25% w/w). Further magnesium stearate addition lead to a slight reduction in nip
angle. This observation contradicts previous investigations which suggest that nip
angle decreases with increasing magnesium stearate concentration [6]. This
disagreement is attributed to the configuration of the roller compactor used. The roller
compactor used utilizes a horizontal force feeding system. Presence of magnesium
stearate reduces the pressure required to increase the bulk density of the powder bed.
This results in a powder bed with higher density in the slip region and hence increases
the pressure applied by the powder bed to the rollers forcing the roll gap to open wider
allowing more powder to pass through the system.
1.000.750.500.250.00
24
23
22
21
20
19
18
17
16
15
1.000.750.500.250.00
7
MgSt Concentration (% w/w)
Nip
An
gle
(d
eg
)
60
45
60
80
110
4. Lubricant Sensitivity
Tablet strength of the uncompacted
formulation (previously tumble blended
for 7 minutes) collected from the
region before the rollers was
compared to that of just blended
formulation. Mixing that occurs within
the feeding system has had a
significant affect on the tablet tensile
strength.
4.0
4.5
5.0
5.5
6.0
6.5
0 20 40 60
Ta
ble
t Te
ns
ile
Str
en
gth
(M
Pa
)
Feed Auger Rotation Speed (rpm)
5. Mass throughput
Addition of magnesium stearate has lead to a significant increase in mass
throughput. Increase in mass throughput was unexpected since addition of
magnesium stearate to the formulation would promote slip between the roll surface
and powder bed and hence theoretically reduce the mass of powder drawn through
the rollers. The extent of mass throughput improvement is largest at magnesium
stearate levels < 0.25% (w/w). Subsequent addition of magnesium stearate shows
little further improvement in the mass throughput. A corresponding increase in roll
gap was observed with increasing mass throughput. Since in-gap ribbon porosity
was found to be constant (for a given set of parameters) at each magnesium
stearate level, this increase in roll gap is directly related to the increase in mass
throughput.
1.000.750.500.250.00
400
350
300
250
200
150
1.000.750.500.250.00
7
MgSt Concentration (% w/w)
Ma
ss
Th
rou
gh
pu
t (g
/min
) 60
25
30
32
34
Screw Speed (rpm)
1.000.750.500.250.00
50403020100
1.000.750.500.250.00
5040302010
0
25
MgSt Concentration (% w/w)
Ma
ss
in
cre
as
e (
%)
30
32 34
7
60
Mixing Time (mins)
8. AcknowledgementsThe authors would like to thank Dr. John Grosso, Dr Nancy Barbour, Dr Peter Timmins, Dr. Enes Supuk, and Mr Martin
Vernon for their support during this study. The authors would also like to acknowledge the Engineering and Physical
Sciences Research Council and Bristol Myers Squibb for their financial support during this project.
9. Literature[1] X. He, P.J. Secreast, G.E. Amidon, “Mechanistic study of the effect of roller compaction and lubricant on tablet mechanical strength”. J. Pharm. Sci 96(5) (2007) 1342-1355.
[2] G. Ragnarsson, A.W. Holzer, J. Sjogren “The influence of mixing time and colloidal silica on the lubricating properties of magnesium stearate”. Int. J. Pharm (1979) 3 127-131.
[3] J. Kushner, F. Moore, “Scale-up model describing the impact of lubrication on tablet tensile strength”. Int. J. Pharm (2010) 399 19-30.
[4] A.M. Miguelez-Moran, C. Y. Wu, H. Dong, and J. P. K Seville. “Characterisation of density distributions in roller compacted ribbons using micro-indentation and X-ray micro-computed tomography”. Eur. J. Pharm. Biopharm 1 (2009) 173-182.
[5] A.M. Miguelez-Moran, C.-Y. Wu, and J.P.K Seville. “The effect of lubrication on desity distributions of roller compacted ribbons”. Int. J. Pharm 362 (2008) 52-59
[6] P. Kleinebudde. “Roll compaction/dry granulation: Pharmaceutical applications”. Eur. J. Pharm. Biopharm 58(2) (2004) 317-326.
Roll Pressure (bar)