1. National Institute for Pharmaceutical Technology and Education (NIPTE) Stability Group - Solid Form Characterization Eric Munson

2. 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)

3. Gabapentin as Received - SSNMR

4. O OH NH 2 1 2 3 4 5 6 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 1 H T 1 = 134 s

5. SSNMR of Gabapentin Forms

6. SSNMR of Gabapentin Forms - Effects of Recrystallization

7. Lot B Lot D Lot A Lot C Intensity (arbitrary units) Two-Theta (deg)

8. SSNMR of Gabapentin Forms - Effects of Recrystallization Lot B Lot D Lot A Lot C Intensity (arbitrary units) Two-Theta (deg)

9. SSNMR of Gabapentin Forms - Effects of Recrystallization Lot A, 20xLot B, 20x Lot C, 10xLot D, 20x

10. SSNMR of Gabapentin Forms

11. SSNMR of Gabapentin Forms - Monohydrate

12. SSNMR of Gabapentin Forms - Milled Samples

15.  Particles of bulk lactose monohydrate before processing  Lactose monohydrate cryoground for 60 minutes Crystallin e Amorphous Effect of Grinding on Forms

16. Lubach, J. W.; Xu, D.; Segmuller, B. E., Munson, E. J. In Press J. Pharm. Sci. 2006. Lactose 1 H T 1 Relaxation Data - SSNMR

17. Lubach, J. W.; Xu, D.; Segmuller, B. E., Munson, E. J. In Press J. Pharm. Sci. 2006. Lactose 1 H T 1 Relaxation Data - SSNMR

18. Gabapentin Relaxation Times Sample 1 H T 1 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

19. Degradation of Gabapentin Forms - Milled Samples

20. Gabapentin Relaxation Times Sample 1 H T 1 Initial Lactam After Stability GBN-MH-081309-UM-AMK-A348 s0.000 082909-1-UI-ZXZ (unmilled, no heat, no moisture)134 s0.000 082909-2-UI-ZXZ (milled, no heat, no moisture)41 s0.0480.109 082909-3-UI-ZXZ (milled, heat, no moisture)61 s0.0980.134 082909-4-UI-ZXZ (milled, heat, moisture)63 s0.0510.060 082909-5-UI-ZXZ (HPC, unmilled)130 s0.0030.011 082909-6-UI-ZXZ (HPC, milled, no heat, no moisture)11 s0.1100.464 082909-7-UI-ZXZ (HPC, milled, heat, no moisture)14 s0.4530.467 082909-8-UI-ZXZ (HPC, milled, heat, moisture)11 s0.0880.119

21. Degradation of Gabapentin Forms - Milled Samples

22. Summary