National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form...
-
Upload
annice-norris -
Category
Documents
-
view
219 -
download
0
Transcript of National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form...
![Page 1: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/1.jpg)
National Institute for Pharmaceutical Technology and Education
(NIPTE)
Stability Group - Solid Form Characterization
Eric Munson
![Page 2: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/2.jpg)
Outline
• Samples of Gabapentin Analyzed
• Gabapentin - multiple forms
• Gabapentin monohydrate/desolvate
• Interconversion of forms upon analysis
• Identification - Form III in milled samples
• Gabapentin Lactam (primary degradation product)
![Page 3: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/3.jpg)
Gabapentin as Received - SSNMR
![Page 4: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/4.jpg)
O
OH
NH2
12
3
456
7
8 9
3
4
2
7(6,8)
(5,9)
Not shown: Carbon 1 at 179.5 ppm
Tentative NMR Assignments
Gabapentin as Received - SSNMR
1H T1 = 134 s
![Page 5: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/5.jpg)
SSNMR of Gabapentin Forms
![Page 6: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/6.jpg)
SSNMR of Gabapentin Forms - Effects of Recrystallization
![Page 7: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/7.jpg)
SSNMR of Gabapentin Forms - Effects of Recrystallization
5 10 15 20 25 30 35
Theta(deg)
x103
50
100
150
200
[Lot_A_UI-a2009-01-21 02.32.51PM.MDI] Lot_A_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=44709, 01/21/09 02:46p[Lot_B_UI-a2009-01-21 02.50.49PM.MDI] Lot_B_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=35959, 01/21/09 03:04p[Lot_C_UI-a2009-01-21 03.08.55PM.MDI] Lot_C_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=110442, 01/21/09 03:22p
Lot B
Lot D
Lot A
Lot C
Inte
nsi
ty (
arb
itra
ry u
nit
s)
Two-Theta (deg)
![Page 8: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/8.jpg)
SSNMR of Gabapentin Forms - Effects of Recrystallization
5 10 15 20 25 30 35
Theta(deg)
0
2500
5000
7500
[Lot_A_UI-a2009-01-21 02.32.51PM.MDI] Lot_A_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=44709, 01/21/09 02:46p[Lot_B_UI-a2009-01-21 02.50.49PM.MDI] Lot_B_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=35959, 01/21/09 03:04p[Lot_C_UI-a2009-01-21 03.08.55PM.MDI] Lot_C_UI-a, SCAN: 5.0/39.992/0.048/1(sec), Cu, I(max)=110442, 01/21/09 03:22p
Lot B
Lot D
Lot A
Lot C
Inte
nsi
ty (
arb
itra
ry u
nit
s)
Two-Theta (deg)
![Page 9: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/9.jpg)
SSNMR of Gabapentin Forms - Effects of Recrystallization
Lot A, 20x Lot B, 20x
Lot C, 10x Lot D, 20x
![Page 10: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/10.jpg)
SSNMR of Gabapentin Forms
![Page 11: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/11.jpg)
SSNMR of Gabapentin Forms - Monohydrate
![Page 12: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/12.jpg)
SSNMR of Gabapentin Forms - Milled Samples
![Page 13: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/13.jpg)
SSNMR of Gabapentin Forms - Milled Samples
![Page 14: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/14.jpg)
SSNMR of Gabapentin Forms - Milled Samples
![Page 15: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/15.jpg)
Particles of bulk lactose monohydrate before processing
Lactose monohydrate cryoground for 60 minutes
120 100 80 40ppm
60 120 100 80 40ppm
60
Crystalline
Crystalline
Amorphous
Effect of Grinding on Forms
![Page 16: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/16.jpg)
Bulk crystalline1H T1 = 243 s
Tablets1H T1 = 79 s
Spray-dried1H T1 = 4.1 s
120 100 80 40ppm
Lyophilized1H T1 = 3.8 s
60
O
OH
OH
H
HO
HH
HO
H
OH
O
OH
OH
H
HH
OHH
HO
H
Lubach, J. W.; Xu, D.; Segmuller, B. E., Munson, E. J. In Press J. Pharm. Sci. 2006.
Lactose 1H T1 Relaxation Data - SSNMR
![Page 17: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/17.jpg)
Lubach, J. W.; Xu, D.; Segmuller, B. E., Munson, E. J. In Press J. Pharm. Sci. 2006.
Lactose 1H T1 Relaxation Data - SSNMR
![Page 18: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/18.jpg)
Gabapentin Relaxation Times
Sample 1H T1
Gabapentin API (Form II) 134 s
122008-UI-SDD-1 (Lot A, Form III) 63 s
010909-UI-ZXZ-1 (Lot B) 128 s
122008-UI-SDD-2 (Lot C) 110 s
010909-UI-ZXZ-2 (Lot A) 131 s
031709-1-UI-SDD (15 min milling) 11.7 s
031709-2-UI-SDD (30 min milling) 14.4 s
031709-3-UI-SDD (45 min milling) 11.2 s
031709-4-UI-SDD (60 min milling) 23.6 s
03009-KU-DBH (10 min cryogrinding) 7.3 s
Stability - High, Medium, Low
![Page 19: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/19.jpg)
Degradation of Gabapentin Forms - Milled Samples
![Page 20: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/20.jpg)
Gabapentin Relaxation Times
Sample 1H T1Initial
LactamAfter
Stability
GBN-MH-081309-UM-AMK-A 348 s 0.000 0.000
082909-1-UI-ZXZ (unmilled, no heat, no moisture) 134 s 0.000 0.000
082909-2-UI-ZXZ (milled, no heat, no moisture) 41 s 0.048 0.109
082909-3-UI-ZXZ (milled, heat, no moisture) 61 s 0.098 0.134
082909-4-UI-ZXZ (milled, heat, moisture) 63 s 0.051 0.060
082909-5-UI-ZXZ (HPC, unmilled) 130 s 0.003 0.011
082909-6-UI-ZXZ (HPC, milled, no heat, no moisture) 11 s 0.110 0.464
082909-7-UI-ZXZ (HPC, milled, heat, no moisture) 14 s 0.453 0.467
082909-8-UI-ZXZ (HPC, milled, heat, moisture) 11 s 0.088 0.119
![Page 21: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/21.jpg)
Degradation of Gabapentin Forms - Milled Samples
![Page 22: National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson.](https://reader035.fdocuments.net/reader035/viewer/2022062805/5697bfe81a28abf838cb64c2/html5/thumbnails/22.jpg)
Summary