AAPS_2012_klucel updated
4
INTRODUCTION Solid dispersion technology is a key enabling technology for bioavailability enhancement of poorly soluble compounds. Research in the past decade in solid dispersions and process technology has established that stable solid dispersions can be prepared at commercial scale through hot-melt extrusion. Polymer selection is critical in producing a successful amorphous solid dispersion that facilitates dissolution and prevents the API recrystallization. In hot-melt extrusion, thermal degradation properties and melt rheology must be considered when selecting a formula. The glass transition temperature, T g , of the polymers defines the lower end of the processing temperature window; typically extrusion is performed at temperatures between 20–40°C above the T g of the polymer. High T g polymers are preferred for physical stability but more difficult to process by melt extrusion without plasticization by adjuvants and/or the API. The thermal degradation properties of the polymer (along with those of the API and any adjuvants) determine the upper process temperatures in melt extrusion. Rheological properties of the polymer melt are important for start-up and steady-state processing; depending on the power of the extruder motor, melt viscosities below 100,000 Pa·s and preferably below 10,000 Pa·s are desired for hot melt extrusion. THERMAL AND RHEOLOGICAL PROPERTIES OF KLUCEL TM HYDROXYPROPYLCELLULOSE POLYMERS FOR HOT-MELT EXTRUSION APPLICATIONS Mohammed Rahman 1 , Elanor Pinto 3 , Seher Ozakan 2 , Kimberly Gaughan 3 , A. Sosnowik 3 James Lester 1 , James Brady 3 , Ishrath Farzana 1 , Robert Sulouff 3 , Vivian Bi 3 and Thomas Dürig 3 1 Ashland Specialty Ingredients,Solubilization Center of Excellence, Columbia, MD 21045, USA; 2 Ashland Specialty Ingredients, Wayne, NJ 07470, USA ; 3 Ashland Specialty Ingredients, Wilmington, DE 19808 USA EXPERIMENTAL METHODS Thermal Gravimetric Analysis TGA experiments were performed using a TA Instruments Q500. Thermal decomposition of Klucel hydroxypropylcellulose (HPC) polymers was characterized by TGA using two methods; first, the sample was heated from ambient to 600°C at different heating rates under air and nitrogen purges. Second, samples were isothermally heated from 140 to 230°C for long term 30 minute heat exposure and short term 5 minute heat exposure. Viscosity Dynamic oscillatory flow tests were carried out in the linear viscoelastic region using a strain-controlled ARES-G2 rheometer equipped with a temperature control chamber (TA instruments). Powder samples were loaded on the 25 mm stainless steel parallel plate set up with the help of a melt ring. Samples were not dried before testing. Dynamic strain sweep, frequency sweep, temperature sweep and time sweep tests were conducted for each sample under nitrogen and air purge. Capillary Rheometry Capillary viscosity experiments were performed using a bench top Rosand RH2200 capillary rheometer with a twin bore configuration. Test materials are placed inside barrels with select dies. During a measurement, two pistons are inserted into the barrels and driven downwards to extrude test materials through the dies. At the bottoms of the barrels and near the die entrances, two pressure transducers measure the pressure drop across the entire die length with respect to the ambient pressure. CONCLUSIONS Higher molecular weight Klucel HPCs are less resistant to thermal degradation and discoloration than lower molecular weight HPCs. Although Klucel HPCs may yellow or brown at relatively low temperatures, Klucel HPCs extruded at temperatures above discoloration temperatures still meet select USP compendial testing such as identification by FTIR, moisture content, viscosity, pH and terminal methyl content. Dynamic oscillatory flow testing suggests that all Klucel HPC polymers can be extruded without the addition of plasticizer; however, only lower molecular weight Klucel HPCs can be extruded below discoloration temperatures without the addition of plasticizer. Melt rheology data below 200 o C suggests that water content could have a significant impact on Klucel HPC melt behavior. Low molecular weight Klucel HPC polymers have ideal rheological and thermal degradation characteristics for hot melt extrusion without plasticization. RESULTS AND DISCUSSION Thermal Degradation & Discoloration by TGA Table 1 describes the various grades of Klucel HPC polymers, their respective molecular weights and aqueous solution viscosities. Figures 1 and 2 illustrate the TGA results for Klucel ELF HPC that was isothermally heated for long term 30 minute isothermal heat exposure at 120°C and 180°C, respectively. Figure 3 shows the resulting color change of long term 30 minute isothermal heat exposure of Klucel ELF HPC between 100°C and 180°C. Klucel ELF HPC shows slight yellow discoloration at 140°C and browning at 150°C. Figures 4 through 12 show similar experiments performed with Klucel LF, JF, and HF HPC. Klucel LF HPC shows a similar temperature induced discoloration profile as Klucel ELF HPC. Klucel JF HPC shows slight yellow discoloration at 160°C and browning by 180°C. Klucel HF HPC shows slight yellow discoloration at 190°C and browning by 200°C. Table 2 shows the temperature induced discoloration profile of Klucel HPCs after long term 30 minute isothermal heat exposure. The overall TGA results of all Klucel HPCs show a 2-3% moisture loss in the first 5-10 minutes of isothermal heating followed by a second less appreciable weight loss (less than 1%) after 10-30 minutes of isothermal heating. The second less appreciable weight loss in isothermal heating is less significant at higher temperatures than lower temperatures, suggesting heat induced degradation. The overall results suggest that higher molecular weight HPCs are less resistant to isothermal degradation and discoloration than lower molecular weight HPCs. Short term 5 minute heat exposure experiments for Klucel HPCs show similar results to the long term 30 minute heat exposure experiments (results not shown.) USP Testing Klucel HPC polymers were processed on a Dynisco ® Laboratory Mixing Extruder at 180°C and tested to ensure that the polymers still met specific USP requirements after being extruded. Fourier Transform Infrared Spectroscopy (FTIR) The infrared spectra were collected employing a Golden Gate diamond ATR accessory mounted in a Nicolet Magna 760 FTIR spectrometer. Quantitative parameters were used for spectrum collection – 4cm -1 resolution, 150 co-added scans (3 minute 45 second collection time), 0.4747 mirror velocity, one level of zero filling and a DTGS detector. Table 1: Klucel HPC Polymers Klucel HPC Grade Typical Weight Avg. Mol. Wt. Solution Viscosity (wt/wt%) (cP) ELF 40,000 * EF 80,000 200-600 (10%) LF 95,000 75-150 (5%) JF 140,000 150-400 (5%) GF 370,000 150-400 (2%) MF 850,000 4000-6500 (2%) HF 1,150,000 1500-3000 (1%) Rheology The melt rheology of neat Klucel HPC polymers was characterized by measuring the melt flow index by capillary rheometry at constant temperature (Figure 15), measuring viscosity at various temperatures (Figure 16), measuring viscosity as a function of shear rate at constant temperature (Figure 17), and measuring viscosity as a function of shear rate at various temperatures (Figures 18-20). As shown in Figure 16, the melt viscosity profile of Klucel HPC polymers suggests that the ideal hot-melt extrusion processing window for these polymers is between ~700 and 100,000 Pa·s while processing below discoloration and degradation temperatures. The temperature sweep data suggests that all Klucel HPC polymers can be extruded below 200 o C; however, the melt viscosity of Klucel HPC polymers does not show a linear correlation with Klucel HPC molecular weight, suggesting that moisture content may be playing a significant role in Klucel HPC melt viscosity. The temperature dependent shear rate versus viscosity data suggests that all Klucel HPC polymers demonstrate classic psuedoplastic behavior wherein increasing shear rate decreases melt viscosity. Increasing temperature of Klucel ELF and HF HPCs significantly reduces melt viscosity but increasing temperature of Klucel MF HPC does not significantly reduce the melt viscosity, suggesting that temperature dependent melt viscosity may not be molecular weight dependent. Figure 16. Klucel HPC temperature sweep. Figure 17. Klucel HPC shear rate vs. viscosity at 200 o C. Figure 1. Klucel ELF HPC, 120°C, N 2 purged 30 minute isothermal TGA -2.8% -0.1% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 92 94 96 98 100 102 Weight (%) 0 5 10 15 20 25 30 35 40 Time (min) Universal V4.7A TA Instruments Figure 2. Klucel ELF HPC, 180°C, N 2 purged 30 minute isothermal TGA -3.0% -0.9% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 92 94 96 98 100 102 Weight (%) 0 5 10 15 20 25 30 35 40 Time (min) Universal V4.7A TA Instruments Figure 15. Effect of Klucel HPC MW on Melt Flow Index at 150 o C Figure 18. Klucel ELF HPC temperature dependent shear rate vs. viscosity. Figure 19. Klucel LF HPC tempera- ture dependent shear rate vs. vis- cosity. Figure 20. Klucel MF HPC temperature dependent shear rate vs. viscosity. Figure 12. Klucel HF HPC, 210°C, N 2 purged 30 minute isothermal TGA -3.6% -0.8% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 92 94 96 98 100 102 Weight (%) 0 5 10 15 20 25 30 35 40 45 Time (min) Universal V4.7A TA Instruments Figure 11. Klucel HF HPC, 180°C, N 2 purged 30 minute isothermal TGA -3.5% -0.4% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 92 94 96 98 100 102 Weight (%) 0 5 10 15 20 25 30 35 40 45 Time (min) Universal V4.7A TA Instruments Figure 3. Klucel ELF HPC, 30 minute exposure to various temperatures. Figure 4. Klucel LF HPC, 30 minute exposure to various temperatures. Figure 10. Klucel HF HPC, 30 minute exposure to various temperatures. Figure 9. Klucel JF HPC, 30 minute exposure to various temperatures. -3.9% -0.5% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 90 92 94 96 98 100 102 Weight (%) 0 10 20 30 40 50 Time (min) Universal V4.7A TA Instruments Figure 8. Klucel JF HPC, 190°C, N 2 purged 30 minute isothermal TGA -3.5% -0.1% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 90 92 94 96 98 100 102 Weight (%) 0 10 20 30 40 50 Time (min) Universal V4.7A TA Instruments Figure 7. Klucel JF HPC, 130°C, N 2 purged 30 minute isothermal TGA Figure 5. Klucel LF HPC, 130°C, N 2 purged 30 minute isothermal TGA -2.5% -0.1% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 90 92 94 96 98 100 102 Weight (%) 0 10 20 30 40 50 Time (min) Universal V4.7A TA Instruments -2.6% -0.5% -0.5 0.0 0.5 1.0 1.5 2.0 [ ] Deriv. Weight (%/min) ––– ––– 90 92 94 96 98 100 102 Weight (%) 0 10 20 30 40 50 Time (min) Universal V4.7A TA Instruments Figure 6. Klucel LF HPC, 170°C, N 2 purged 30 minute isothermal TGA Figure 14. Infrared spectra comparing Klucel MF HPC reference and Klucel MF HPC extruded at 230°C Figure 13. Infrared spectra comparing Klucel MF HPC reference and Klucel MF HPC extruded at 200°C Select Compendial Testing Klucel ELF and HF HPC were processed on the Dynisco LME at 180°C and the resulting extrudates were found to be within USP compendia specification for FTIR, moisture, viscosity, pH, and terminal methyl content. Klucel MF and HF HPC were also processed on the Dynisco LME at 200°C and 230°C and the resulting extrudate showed no significant change compared to the respective reference FTIR spectrum, as shown if Figures 13 and 14. Table 2: Klucel HPC Heat Induced Discoloration Profile Klucel HPC Grade Yellowing Temperature ( o C) Browning Temperature ( o C) ELF 140 150 EF 140 160 LF 140 170 JF 160 180 GF 180 210 MF 190 210 HF 190 210
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Transcript of AAPS_2012_klucel updated
INTRODUCTION Solid dispersion technology is a key enabling technology for bioavailability enhancement of poorly soluble compounds. Research in the past decade in solid dispersions and process technology has established that stable solid dispersions can be prepared at commercial scale through hot-melt extrusion. Polymer selection is critical in producing a successful amorphous solid dispersion that facilitates dissolution and prevents the API recrystallization. In hot-melt extrusion, thermal degradation properties and melt rheology must be considered when selecting a formula. The glass transition temperature, Tg, of the polymers defines the lower end of the processing temperature window; typically extrusion is performed at temperatures between 20–40°C above the Tg of the polymer. High Tg polymers are preferred for physical stability but more difficult to process by melt extrusion without plasticization by adjuvants and/or the API. The thermal degradation properties of the polymer (along with those of the API and any adjuvants) determine the upper process temperatures in melt extrusion. Rheological properties of the polymer melt are important for start-up and steady-state processing; depending on the power of the extruder motor, melt viscosities below 100,000 Pa·s and preferably below 10,000 Pa·s are desired for hot melt extrusion.
THERMAL AND RHEOLOGICAL PROPERTIES OF KLUCELTM
HYDROXYPROPYLCELLULOSE POLYMERS FOR HOT-MELT EXTRUSION APPLICATIONS
Mohammed Rahman1, Elanor Pinto
3, Seher Ozakan
2, Kimberly Gaughan
3, A. Sosnowik
3 James Lester
1, James Brady
3, Ishrath Farzana
1, Robert Sulouff
3,
Vivian Bi3 and Thomas Dürig
3
1Ashland Specialty Ingredients,Solubilization Center of Excellence, Columbia, MD 21045, USA;
2Ashland Specialty Ingredients, Wayne, NJ 07470, USA ;
3Ashland Specialty Ingredients, Wilmington, DE 19808 USA
EXPERIMENTAL METHODS
Thermal Gravimetric Analysis TGA experiments were performed using a TA Instruments Q500. Thermal decomposition of Klucel hydroxypropylcellulose (HPC) polymers was characterized by TGA using two methods; first, the sample was heated from ambient to 600°C at different heating rates under air and nitrogen purges. Second, samples were isothermally heated from 140 to 230°C for long term 30 minute heat exposure and short term 5 minute heat exposure.
Viscosity Dynamic oscillatory flow tests were carried out in the linear viscoelastic region using a strain-controlled ARES-G2 rheometer equipped with a temperature control chamber (TA instruments). Powder samples were loaded on the 25 mm stainless steel parallel plate set up with the help of a melt ring. Samples were not dried before testing. Dynamic strain sweep, frequency sweep, temperature sweep and time sweep tests were conducted for each sample under nitrogen and air purge.
Capillary Rheometry Capillary viscosity experiments were performed using a bench top Rosand RH2200 capillary rheometer with a twin bore configuration. Test materials are placed inside barrels with select dies. During a measurement, two pistons are inserted into the barrels and driven downwards to extrude test materials through the dies. At the bottoms of the barrels and near the die entrances, two pressure transducers measure the pressure drop across the entire die length with respect to the ambient pressure.
CONCLUSIONS Higher molecular weight Klucel HPCs are less resistant to thermal degradation and discoloration than lower molecular weight HPCs. Although Klucel HPCs may yellow or brown at relatively low temperatures, Klucel HPCs extruded at temperatures above discoloration temperatures still meet select USP compendial testing such as identification by FTIR, moisture content, viscosity, pH and terminal methyl content. Dynamic oscillatory flow testing suggests that all Klucel HPC polymers can be extruded without the addition of plasticizer; however, only lower molecular weight Klucel HPCs can be extruded below discoloration temperatures without the addition of plasticizer. Melt rheology data below 200
oC suggests that
water content could have a significant impact on Klucel HPC melt behavior. Low molecular weight Klucel HPC polymers have ideal rheological and thermal degradation characteristics for hot melt extrusion without plasticization.
RESULTS AND DISCUSSION
Thermal Degradation & Discoloration by TGA Table 1 describes the various grades of Klucel HPC polymers, their respective molecular weights and aqueous solution viscosities.
Figures 1 and 2 illustrate the TGA results for Klucel ELF HPC that was isothermally heated for long term 30 minute isothermal heat exposure at 120°C and 180°C, respectively. Figure 3 shows the resulting color change of long term 30 minute isothermal heat exposure of Klucel ELF HPC between 100°C and 180°C. Klucel ELF HPC shows slight yellow discoloration at 140°C and browning at 150°C. Figures 4 through 12 show similar experiments performed with Klucel LF, JF, and HF HPC. Klucel LF HPC shows a similar temperature induced discoloration profile as Klucel ELF HPC. Klucel JF HPC shows slight yellow discoloration at 160°C and browning by 180°C. Klucel HF HPC shows slight yellow discoloration at 190°C and browning by 200°C. Table 2 shows the temperature induced discoloration profile of Klucel HPCs after long term 30 minute isothermal heat exposure. The overall TGA results of all Klucel HPCs show a 2-3% moisture loss in the first 5-10 minutes of isothermal heating followed by a second less appreciable weight loss (less than 1%) after 10-30 minutes of isothermal heating. The second less appreciable weight loss in isothermal heating is less significant at higher temperatures than lower temperatures, suggesting heat induced degradation. The overall results suggest that higher molecular weight HPCs are less resistant to isothermal degradation and discoloration than lower molecular weight HPCs. Short term 5 minute heat exposure experiments for Klucel HPCs show similar results to the long term 30 minute heat exposure experiments (results not shown.)
USP Testing Klucel HPC polymers were processed on a Dynisco
® Laboratory
Mixing Extruder at 180°C and tested to ensure that the polymers still met specific USP requirements after being extruded.
Fourier Transform Infrared Spectroscopy (FTIR) The infrared spectra were collected employing a Golden Gate diamond ATR accessory mounted in a Nicolet Magna 760 FTIR spectrometer. Quantitative parameters were used for spectrum collection – 4cm
-1
resolution, 150 co-added scans (3 minute 45 second collection time), 0.4747 mirror velocity, one level of zero filling and a DTGS detector.
Table 1: Klucel HPC Polymers
Klucel HPC
Grade
Typical Weight Avg. Mol.
Wt.
Solution Viscosity (wt/wt%)
(cP)
ELF 40,000 *
EF 80,000 200-600 (10%)
LF 95,000 75-150 (5%)
JF 140,000 150-400 (5%)
GF 370,000 150-400 (2%)
MF 850,000 4000-6500 (2%)
HF 1,150,000 1500-3000 (1%)
Rheology The melt rheology of neat Klucel HPC polymers was characterized by measuring the melt flow index by capillary rheometry at constant temperature (Figure 15), measuring viscosity at various temperatures (Figure 16), measuring viscosity as a function of shear rate at constant temperature (Figure 17), and measuring viscosity as a function of shear rate at various temperatures (Figures 18-20). As shown in Figure 16, the melt viscosity profile of Klucel HPC polymers suggests that the ideal hot-melt extrusion processing window for these polymers is between ~700 and 100,000 Pa·s while processing below discoloration and degradation temperatures. The temperature sweep data suggests that all Klucel HPC polymers can be extruded below 200
oC; however, the
melt viscosity of Klucel HPC polymers does not show a linear correlation with Klucel HPC molecular weight, suggesting that moisture content may be playing a significant role in Klucel HPC melt viscosity. The temperature dependent shear rate versus viscosity data suggests that all Klucel HPC polymers demonstrate classic psuedoplastic behavior wherein increasing shear rate decreases melt viscosity. Increasing temperature of Klucel ELF and HF HPCs significantly reduces melt viscosity but increasing temperature of Klucel MF HPC does not significantly reduce the melt viscosity, suggesting that temperature dependent melt viscosity may not be molecular weight dependent.
Figure 16. Klucel HPC temperature sweep.
Figure 17. Klucel HPC shear rate vs. viscosity at 200
oC.
Figure 1. Klucel ELF HPC, 120°C, N2
purged 30 minute isothermal TGA
-2.8%
-0.1%
-0.5
0.0
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1.0
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Sample: X35319-4G Klucel HPC ELF
Size: 14.8220 mg
Method: Ramp-Iso 20-120°C
Comment: Lot # 13930
TGA
File: J:...\QTGA ISO X35319-4G N2.120
Operator: Q5000 IR 0466
Run Date: 01-Jun-2012 14:16
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 2. Klucel ELF HPC, 180°C, N2
purged 30 minute isothermal TGA
-3.0%
-0.9%
-0.5
0.0
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Time (min)
Sample: X35319-4G Klucel HPC ELF
Size: 16.3320 mg
Method: Ramp-Iso 20-180°C
Comment: Lot # 13930
TGA
File: J:...\QTGA ISO X35319-4G N2.180
Operator: Q5000 IR 0466
Run Date: 04-Jun-2012 08:37
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 15. Effect of Klucel HPC MW on Melt Flow Index at 150
oC
Figure 18. Klucel ELF HPC temperature dependent shear rate vs. viscosity.
Figure 19. Klucel LF HPC tempera-ture dependent shear rate vs. vis-cosity.
Figure 20. Klucel MF HPC temperature dependent shear rate vs. viscosity.
Figure 12. Klucel HF HPC, 210°C, N2
purged 30 minute isothermal TGA
-3.6%
-0.8%
-0.5
0.0
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1.5
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Time (min)
Sample: X35320-60-1 Klucel HPC HF
Size: 14.9890 mg
Method: Ramp-Iso 20-210°C
Comment: Lot # 15052
TGA
File: J:...\QTGA ISO X35320-60-1 N2.210
Operator: Q5000 IR 0466
Run Date: 04-Jun-2012 17:10
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 11. Klucel HF HPC, 180°C, N2
purged 30 minute isothermal TGA
-3.5%
-0.4%
-0.5
0.0
0.5
1.0
1.5
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/min
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Time (min)
Sample: X35320-60-1 Klucel HPC HF
Size: 15.0100 mg
Method: Ramp-Iso 20-180°C
Comment: Lot # 15052
TGA
File: J:...\QTGA ISO X35320-60-1 N2.180
Operator: Q5000 IR 0466
Run Date: 04-Jun-2012 18:35
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 3. Klucel ELF HPC, 30 minute exposure to various temperatures.
Figure 4. Klucel LF HPC, 30 minute exposure to various temperatures.
Figure 10. Klucel HF HPC, 30 minute exposure to various temperatures.
Figure 9. Klucel JF HPC, 30 minute exposure to various temperatures.
-3.9%
-0.5%
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Time (min)
Sample: X35319-4C Klucel JF
Size: 15.2100 mg
Method: Ramp-Iso 20-190°C
Comment: Lot # 14521
TGA
File: J:...\QTGA ISO X35319-4C N2.190
Operator: Q5000 IR 0466
Run Date: 21-Jun-2012 18:14
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 8. Klucel JF HPC, 190°C, N2
purged 30 minute isothermal TGA
-3.5%
-0.1%
-0.5
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Time (min)
Sample: X35319-4C Klucel JF
Size: 15.3340 mg
Method: Ramp-Iso 20-130°C
Comment: Lot # 14521
TGA
File: J:...\QTGA ISO X35319-4C N2.130
Operator: Q5000 IR 0466
Run Date: 21-Jun-2012 14:05
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 7. Klucel JF HPC, 130°C, N2
purged 30 minute isothermal TGA
Figure 5. Klucel LF HPC, 130°C, N2
purged 30 minute isothermal TGA
-2.5%
-0.1%
-0.5
0.0
0.5
1.0
1.5
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Time (min)
Sample: X35319-4E Klucel LF
Size: 14.8920 mg
Method: Ramp-Iso 20-130°C
Comment: Lot # 14587
TGA
File: J:...\QTGA ISO X35319-4E N2.130
Operator: Q5000 IR 0466
Run Date: 27-Jun-2012 13:49
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
-2.6%
-0.5%
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Sample: X35319-4E Klucel LF
Size: 14.6040 mg
Method: Ramp-Iso 20-170°C
Comment: Lot # 14587
TGA
File: J:...\QTGA ISO X35319-4E N2.170
Operator: Q5000 IR 0466
Run Date: 27-Jun-2012 13:07
Instrument: TGA Q5000 V3.13 Build 261
Universal V4.7A TA Instruments
Figure 6. Klucel LF HPC, 170°C, N2
purged 30 minute isothermal TGA
Figure 14. Infrared spectra comparing Klucel MF HPC reference and Klucel MF HPC extruded at 230°C
Figure 13. Infrared spectra comparing Klucel MF HPC reference and Klucel MF HPC extruded at 200°C
Select Compendial Testing Klucel ELF and HF HPC were processed on the Dynisco LME at 180°C and the resulting extrudates were found to be within USP compendia specification for FTIR, moisture, viscosity, pH, and terminal methyl content. Klucel MF and HF HPC were also processed on the Dynisco LME at 200°C and 230°C and the resulting extrudate showed no significant change compared to the respective reference FTIR spectrum, as shown if Figures 13 and 14.
Table 2: Klucel HPC Heat Induced Discoloration Profile
Klucel HPC Grade Yellowing
Temperature (oC)
Browning
Temperature (oC)
ELF 140 150
EF 140 160
LF 140 170
JF 160 180
GF 180 210
MF 190 210
HF 190 210
