Study on the Blend of Kollidon SR and Ibuprofen Using Hot Melt Extrusion
Gowri Dorairaju, Brian LaBrec, Anthony Listro, Lawrence Acquarulo
Foster Corporation, Putnam CT – 06260
Background
Experimental Method - Characterization
Melt extrusion offers many benefits over traditional processing techniques used in the pharmaceutical
industry. The process is performed at elevated temperatures, but the residence time in which the ingredients
exposed to the elevated temperature is very short. In addition, potential drug degradation can be avoided since the
process is anhydrous.
Kollidon SR is a copolymer of polyvinyl acetate and poly vinyl pyrrolidone and it is particularly suitable for
the manufacture of pH-independent sustained release matrix tablets. When the tablets are introduced into gastric or
intestinal fluid, the water soluble povidone is leached out to form pores through which the active ingredient slowly
diffuses outwards. Kollidon SR contains no ionic groups and is therefore inert to drug substances.
Thermal Analysis
The characterization study was performed on the neat polymer Kollidon SR, Active ingredient Ibuprofen, and
the extruded samples of Kollidon SR and the blend compound (Kollidon SR and Ibuprofen), processed at 135° C.
The TGA analysis was performed in the presence of nitrogen at a scan rate of 10° C/min from 30° C to 600° C. The
conventional DSC analysis (Ramp method) was done at a scan rate of 10° C/min from the room temperature (25° C
to 30° C) to the decomposition temperature of each material.
80
40
60
30
40
20
20
10
0
0
125
Figure 1: Structure of Ibuprofen
130
Figure 2: Structure of Kollidon
Ibuprofen is a non-steroidal anti inflammatory drug (NSAIDs) C13H18O2, used especially in the treatment
of arthritis. The chemical name of the compound is 2-[4-(2-methylpropyl) phenyl] propanoic acid. Ibuprofen is
used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back
pain, arthritis, menstrual cramps, or minor injury.
Objective
The objective of the research work is to study the behavior of the blend of polymer, Kollidon SR 20 and the
active ingredient Ibuprofen, when hot melt extruded. Thermal characteristics like Thermo Gravimetric Analysis
(TGA) and Differential Scanning Calorimeter were performed on these samples.
135
140
145
150
Temperature, Deg C
155
Torque_Without IBU Profen
Torque_With IBU Profen
Pressure_Without IBU Profen
Pressure_With IBU Profen
Presuure, bar
Torque, Ncm
Results
a) 160 ° C
b) 155 ° C
c) 150 ° C
d) 145 ° C
b) 155 ° C
c) 150 ° C
d) 145 ° C
160
e) 140 ° C
Figure 4: Torque and Pressure Readings at different Temperatures
Glass
Peak Melting Decomposition
Transition
Temperature, Temperature,
Temperature,
°C
°C
°C
f) 135 ° C
g) 130 ° C
h) 125 ° C
e) 140 ° C
Figure 6: Extruded Kollidon Samples at Different Temperatures
f) 135 ° C
g) 130 ° C
h) 125 ° C
Figure 7: Extruded Blend Samples at Different Temperatures
Temperature
at maximum
degradation
rate, ° C
S.No
Material
1
Ibuprofen
46.41
74.81
145.07
202.09
2
Kollidon
40.08
N/A
295.07
333.08 and
442.14
3
Extruded
Kollidon
31.84
N/A
275.84
331.06 and
441.31
4
Blend
22.25
N/A
193.76
329.62 and
433.46
Figure 8: TGA Graph for Different Materials
Figure 9: Derivative TGA Graph for Different Materials
Table 1: Thermal Characteristics Data for different materials
Equipment and Materials
Melting of polymorphs that formed
while heating / extruding
Equipment:
Minilab Extruder (Manufacturer: Thermo Fischer)
TA Instruments
Materials:
Kollidon SR 20 (Mfg: BASF)
Ibuprofen (Mfg: Spectrum Chemicals)
Blend Composition:
Kollidon: Ibuprofen – 80:20 (Wt%)
a) 160 ° C
Water evaporation
Glass Transition with enthalpy
recovery / water evaporation
Figure 10: DSC Curve for Ibuprofen
Figure 11: DSC Curve for Kollidon and Extruded Kollidon
Figure 12: Comparison of DSC Curve for Different Materials
Conclusion & Future Works
Figure 3: Thermo Fischer - Mini Lab Extruder
Experimental Method - Extrusion
Processing
The Kollidon and Ibuprofen drug were prepared according to the blend Composition. The Kollidon and the
blend were fed to the extruder and they were extruded at different temperatures ranging from 125 °C to 160° C in
an increment of 5 °C. For each trial, the torque and pressure were recorded.
Conclusion:
• Ibuprofen sample contains crystallinity whereas the blend (Ibuprofen + Kollidon) does not contain any
crystallinity.
• Blend characteristic curve resembles the amorphous material. The blend is miscible and forms a single phase
when extruded in Minilab at a temperature of 135° C.
• The presence of Ibuprofen acts as a plasticizer and thus reduces the glass transition temperature of the blend.
The torque and the pressure are decreased when Ibuprofen is used.
Future Works:
• Extrude the samples at different ratios and compare the transitions.
• Perform the dissolution testing for the samples.
The authors acknowledge Thermo Fischer and Center for High - Rate Nanomanufacturing (CHN) , University of Massachusetts Lowell for providing the equipments