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Softgel Technologies"
Softigel by Procaps
@SoftigelProcaps
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Softigel by Procaps
Gummy Gels by Procaps
www.softigel.com
About Procaps
Latin America's largest softgel producer with facilities in
Brazil, Colombia and Venezuela, and exports reaching
more than 42 countries worldwide.
Deep knowledge in gelatin formulation and an
impressive scientific expertise in softgel technologies.
Specialized in innovative softgel associated technologies
such as UnigelTM, VersagelsTM, G- tabsTM & GummygelsTM.
We cater to multinational pharmaceutical clients,
including Pfizer, Glaxo Smith Kline, Sanofi-Aventis,
Behringer Ingelheim, and Bayer among others.
Content
1. Introduction
2. Dynamic equilibrium of soft capsules
3. Cross-Linking
4. Recommended additional tests during stability
5. Conclusions
Hydrophillic
Lipophillic
Mixed Matrix
Tablets!
Capsules!
Pellets!
Suspension
Solution
Emulsion
Gelatin/non-Gelatin
Plasticizers
Water
VersagelsTM
Enteric Coating
FILL
Opacifiers
Flavors
Colors (one or two)
Manufacturing workflow.
FILL
Fill preparation
FILL PUMP
LEADS
FEEDER ROLLS
INJECTION WEDGE
RIBBON GUIDES
RIBBON
Encapsulation
TUBE
DIE
DIE
CHUTE
Drying
SPREADER
BOX
DRUM
NET
OIL ROLLS
Finishing
CAPSULE
CONVEYOR
Schematic drawing of a rotary-die soft gelatin capsule filler (R.P. Scherer: Detroit, MI)
FILL TANK
Dynamic Equilibrium
of soft capsules
Secondary Drying
After secondary drying
(Equilibrium)
PEG Fill
-1,2%
PEG Fill
-16%
PEG Fill
-8%
3
Mixed MC
Triglycerides
Fill -0,15%
Mixed MC
Triglycerides
Fill -4,6%
Mixed MC
Triglycerides
Fill -2,4%
3
MCT/LCT
Fill -0,1%
MCT/LCT
Fill -0,1%
3
MCT/LCT
Fill -0,1%
Review Soft Gelatin Capsules (Softgels) Rampurna Prasad Gullapalli Elan Pharmaceuticals, 800 Gateway Blvd., South San Francisco, California 94080
Atmospheric Moisture
k1
Gelatin
k3
k2
k4
k5
k6
k10
Water
k11
k12
e
Dy
k13
MCT/LCT
Fill -0,1%
MCT/LCT
Fill -0,1%
3
104
525,0
102
100,5
100
99,7
498,4
502,6
99,6
98
501,7
505,0
mg
% of label
MCT/LCT
Fill -0,1%
96
95,7
485,0
478,0
465,0
94
445,0
92
90
Month
Assay Through Stability
425,0
Month
Net Weight Through Stability
Capsule No.
Total Weight
(mg)
Shell Weight
(mg)
Capsule No.
Total Weight
(mg)
Shell Weight
(mg)
Net Weight
(mg)
804.0
301.9
502.1
808.4
333.7
474.7
816.6
316.5
500.1
822.0
337.8
484.2
798.8
298.9
499.9
800.6
329.6
471.0
844.3
334.6
509.7
824.6
355.7
468.9
823.4
322.6
500.8
833.6
335.8
497.8
814.2
314.7
499.5
832.1
365.8
466.3
809.8
310.9
498.9
810.5
333.3
477.2
821.0
323.6
497.4
834.6
339.9
494.7
835.6
330.0
505.6
833.2
345.7
487.5
10
835.3
324.6
510.7
10
823.4
365.8
457.6
Average
820.3
317.8
502.5
Average
822.3
344.3
478.0
MIN
798.8
298.9
497.4
MIN
800.6
329.6
457.6
MAX
844.3
334.6
510.7
MAX
834.6
365.8
497.8
SD
14.66
11.56
4.62
SD
12.04
13.50
12.89
RSD
1.8
3.6
0.9
RSD
1.5
3.9
2.7
% of label
102
Normally, glycerin is
used as a plasticizer for
this formulations and it
is very hygroscopic.
100,6
100,5
99,7
100
99,3
99,6
98
96
95,7
94
92
90
4
Month
PEG Fill
-1,2%
PEG Fill
-16%
PEG Fill
-8%
3
Month
Method 1
Method 2
Method 3
96.9 (0.3)
99.8 (0.5)
101.3 (1.2)
96.5 (0.6)
99.2 (0.6)
99.6 (1.3)
95.1 (0.5)
99.5 (0.5)
103.2 (1.2)
94.0 (1.2)
98.9 (0.3)
101.7 (2.1)
Cross-Linking
Cross-Linking
Depending on the involved reactions,
cross-linking is evidenced on different part of the capsules:
Shell
Fill Content
Self
g
n
i
k
in
L
s
s
Cro
Fill Content
Fill Content
Insoluble membrane
between fill and shell
(PELLICLE)
Chem
ic
Cros ally Indu
s-Lin
c
king ed
Cross-Linking
PELLICLES
STICKY MASS
Cross-Linking
Considerations
110
100
90
% Dissolved
90
86
80
70
56
60
50
S1-Initial
S2-Initial
S3-Initial
S1-1 Month
S2-1 Month
S3-1 Month
53
40
30
23
20
10
0
10
15
20
25
30
35
Time (minutes)
40
45
50
Recommended Additional
Tests During Stability
Recommended Additional
Tests During Stability
Weight variation, monitoring
total, shell and net weights.
Shell moisture content.
Fill content moisture.
Rupture time/Disintegration.
Drug substance migration into
the shell.
Shell hardness.
Blooming.
Conclusions
Conclusions
Soft gelatin capsule is a unique dosage
form where dynamic equilibrium affect both
shell and fill composition.
Final equilibrium should be reached after
drying, but depends on formulation and/or
process, it can continue through shelf-life.
Analytical approaches need to take into
account migration phenomena, in order to
avoid either low or high variable results.
According to the approach, strategy for
validation need to be adjusted, in order to
actually verify the capabilities of the
proposed method for the intended purpose.
500
36+Years of experience
243+
softgel formulations
8+
Leading softgel
technologies
11
billion doses of
annual capacity
Versatile technology
that provides compatibility with
high pH formulations and a broader
range of fill excipients.
@SoftigelProcaps
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#cphiww
#speakerscorner
Softigel by Procaps
Softigel by Procaps
Download our app
Softigel by Procaps
Gummy Gels by Procaps
www.softigel.com
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"Innovating in Advanced
Softgel Technologies"