gabapentin tableting studies
DESCRIPTION
Gabapentin Tableting Studies. 96251-2 96251-3 96251-4 96251-5 96251-6 96251-7 96251-8 96251-9 96251-10 96251-11 96251-12 96251-13 96251-14 96251-15. Materials. Granulations: manufactured at Abbott May 27 th & 28 th , 2010 Temp.:23 & 21 ℃ R.H.:54 & 56%. Methods: Tableting. - PowerPoint PPT PresentationTRANSCRIPT
Gabapentin Tableting Studies
Materials• 96251-2• 96251-3• 96251-4• 96251-5• 96251-6• 96251-7• 96251-8• 96251-9• 96251-10• 96251-11• 96251-12• 96251-13• 96251-14• 96251-15
Granulations: manufactured at AbbottMay 27th & 28th, 2010Temp.:23 & 21℃R.H.:54 & 56%
Methods: Tableting• Press– 10-station, instrumented tablet press
• Piccola rotary tablet press (Model B, Knoll pharmaceutical Co., Argetina)
– Instrumentation• Tablet compression
– Tooling• one set punch die set • concave oval (L 17.45 mm, W 10.35mm) shape
– Speed• 25 RPM
• Peak compression force– Granulation 2,3 &12 ca 20, 15, 10 and 5 KN– Other granulations ca 20 KN
Phase / Run Time Pressure Sample Numbers
Phase 1 / ~ 1 min Lead-in Sample 1(S1)
Phase 2 / 2-6 min Comp force 1(~20kN) Samples 2-6(S2-S6), each collected over 1 minute
Phase 3 / ~1 min Adjust Force 1 to Force 2 Sample 8(S8)
Phase 4 / 8-13 min Comp force 2(~15kN) Samples 9-14, each collected over 1 minute
Phase 5 / ~1min Adjust Force 2 to Force 3 Sample 15(S15)
Phase 6 / 16-17 min Comp force 3(~10kN) Samples 16-21(S16-S21), each collected over 1 minute
Phase 7 / ~1min Adjust Force 3 to Force 4 --- Sample 22(S22)
Phase 8 / 19-23 min Comp force 4(~5kN) Samples 23-28(S23-S28), each collected over 1 minute
96251-2, 96251-3 and 96251-12 Sample collecting strategy
Rest of the granulationsPhase / Run Time Pressure Sample Numbers
Phase 1 / ~ 1 min Lead-in Sample 1(S1)
Phase 2 / 2-7 min Comp force 1(~20KN) Samples 2-7(S2-S7), each collected over 1 minute
Weight and weight variation of the 14 granulations at different pressures-- within 2%
96251-2(CF1)
96251-2(CF2)
96251-2(CF3)
96251-2(CF4)
96251-3(CF1)
96251-3(CF2)
96251-3(CF3)
96251-3(CF4)
Avg. 0.8942 0.9005 0.9015 0.8852 0.9016 0.8848 0.8821 0.8832
C.V.(%) 0.5491 0.3399 0.2074 0.3257 0.2944 0.3839 0.4249 0.5371
96251-4 96251-5 96251-6 96251-7 96251-8 96251-996251-
1096251-
11
Avg. 0.9121 0.8971 0.8825 0.8965 0.8953 0.8983 0.9234 0.8840
C.V.(%) 0.3529 0.3605 1.1122 0.5664 0.6197 0.5366 0.5044 0.2963
96251-12(CF1)
96251-12(CF2)
96251-12(CF3)
96251-12(CF4)
96251-13
96251-14
96251-15
Avg. 0.8876 0.8912 0.8916 0.8858 0.8957 0.8948 0.8857
C.V.(%) 0.4754 0.5188 0.6250 0.2910 0.4743 0.3493 0.4936
Pmax vs Breaking force
Compression force vs. Breaking force
0
5
10
15
20
0 5 10 15 20 25
Compression Force (kN)
Brea
king
For
ce (k
P) 96251-2
96251-3
96251-12
The comparison of breaking forces of 14 granulations under similar compression
force(~20kN) 96251-
2 96251-3 96251-4 96251-5 96251-6 96251-7 96251-8
Compression Force(kN) 19.24 18.45 19.50 20.97 20.30 20.81 18.87
S.D. 0.45 0.38 0.60 0.72 0.78 0.96 0.51
Breaking force (kP) 12.32 9.49 12.59 12.14 10.75 13.06 14.53
S.D. 0.60 0.53 0.57 0.49 0.54 0.32 0.58
96251-
996251-
1096251-
1196251-
1296251-
1396251-
1496251-
15
Compression Force(kN) 21.08 20.44 19.74 18.91 20.15 21.01 20.09
S.D. 0.76 0.51 0.28 0.69 0.74 0.46 0.30
Breaking force (kP) 15.00 13.56 13.39 15.26 15.69 15.48 15.84
S.D. 0.40 0.51 0.44 0.64 0.43 0.90 0.48
Methods
• Disintegration– Medium: distilled water– Temp: 37oC– Apparatus: USP<701>
June 17th, 2010 96251-2-7 R.T.: 21°C R.H.(%): 61% June 18th, 2010 96251-8-15 R.T.: 22°C R.H.(%): 54%
Disintegration Time96251-2(CF1) 96251-3(CF1) 96251-4 96251-5 96251-12(CF1) 96251-13
Average 24.05666667 5.380555556 9.886111 8.638889 13.81944444 13.30222
S.D. 1.214786675 0.925887962 0.419049 0.457611 1.03276418 0.398367
C.V.(%) 5.049688272 17.20803647 4.238762 5.2971 7.473268439 2.994741
96251-2(CF2) 96251-3(CF2) 96251-6 96251-7 96251-12(CF2) 96251-14
Average 20.25166667 2.641666667 6.322222 7.541667 11.04722222 14.94722
S.D. 1.423691212 0.337103677 0.508884 0.312294 0.663359854 1.017099
C.V.(%) 7.029995285 12.76102246 8.049132 4.14092 6.004766094 6.804603
96251-2(CF3) 96251-3(CF3) 96251-8 96251-9 96251-12(CF3) 96251-15
Average 13.34333333 1.822222222 18.64167 10.68333 5.080555556 14.98611
S.D. 1.983665518 0.262819471 0.656739 0.494862 0.666701388 1.078086
C.V.(%) 14.86634163 14.42301972 3.522961 4.632098 13.12260796 7.193898
96251-2(CF4) 96251-3(CF4) 96251-10 96251-11 96251-12(CF4)
Average 71.51111111 3.755555556 9.086111 12.50278 3.463888889
S.D. 0.117062819 0.711701144 2.923476 0.814072 0.516765224
C.V.(%) 0.163698784 18.95062218 32.17522 6.511128 14.91864318
Materials
• 96251-21• 96251-22• 96251-23• 96251-24• 96251-25• 96251-27
Granulations: manufactured at AbbottJune 23th & 48th, 2010Temp.:21 ℃R.H.:59%
Methods: Tableting• Press– 35-station, no instrumentation• Manesty BB4 rotary tablet press
(OYSTAR USA, NJ, USA)– Instrumentation
• Tablet compression– Tooling• Seven set punch die set • Concave oval (L 17.45 mm, W 10.35mm) shape
– Speed• 25 RPM
• Peak compression force– Granulation 22, four levels, targeted breaking force: 15, 10,
7 & 3kP– Other granulations targeted breaking force 10kP
Sample collecting strategy for 96251-22
Phase / Run Time Pressure Sample Numbers
Phase 1 / ~ 1 min Lead-in Sample 1(S1)
Phase 2 / 2-6 min Comp force 1(breaking force ~3kP)
Samples 2-6(S2-S6), each collected over 1 minute
Phase 3 / ~1 min Adjust Force 1 to Force 2 Sample 8(S8)
Phase 4 / 8-13 min Comp force 2(breaking force ~7kP)
Samples 9-14, each collected over 1 minute
Phase 5 / ~1min Adjust Force 2 to Force 3 Sample 15(S15)
Phase 6 / 16-17 min Comp force 3(breaking force ~10kP)
Samples 16-21(S16-S21), each collected over 1
minute
Phase 7 / ~1min Adjust Force 3 to Force 4 --- Sample 22(S22)
Phase 8 / 19-23 min Comp force 4(breaking force~14kP)
Samples 23-28(S23-S28), each collected over 1
minute
Sample collecting strategy for the rest of granulations
Phase / Run Time Pressure Sample Numbers
Phase 1 / 1-4 min Comp force 1 (~breaking force 10kP)
Sample 1(S1)
Phase 2 / 5-8 min Comp force 1 Samples 2(S2)
Phase 2 / 9-12 min Comp force 1 Samples 3(S3)
Phase 2 / 13-16 min Comp force 1 Samples 4(S4)
Phase 2 / 17-20 min Comp force 1 Samples 5(S5)
Phase 2 / 21-24 min Comp force 1 Samples 6(S6)
Phase 2 / 23-28 min Comp force 1 Samples 7(S7)
Weight and weight variation of the 6 granulations at different pressures-- within 2%
Weight(g)
96251-21
96251-22(CF1)
96251-22(CF2)
96251-22(CF3)
96251-22(CF4)
96251-23
96251-24
96251-25
96251-27
Avg.0.912
0 0.8959 0.8912 0.8979 0.9030 0.9061 0.8977 0.9090 0.8997
S.D.0.004
8 0.0024 0.0057 0.0034 0.0057 0.0098 0.0060 0.0099 0.0055
C.V.(%)
0.5260 0.2664 0.6340 0.3737 0.6342 1.0787 0.6666 1.0911 0.6058
Methods
• Disintegration– Medium: distilled water– Temp: 37oC– Apparatus: USP<701>
July 15th, 2010 96251-2-7 Temp: 22°C R.H.(%): 69%
Disintegration Time
96251-21
96251-22(CF1)
96251-22(CF2)
96251-22(CF3)
96251-22(CF4)
96251-23
96251-24
96251-25
96251-27
Avg. 45.82 17.75 16.76 23.88 24.93 19.27 20.88 18.43 25.60
S.D. 13.28 1.41 2.36 1.82 3.30 3.51 5.11 1.14 8.24
C.V.(%) 28.99 7.95 14.09 7.62 13.24 18.24 24.45 6.21 32.17
• Disintegration data for Rutgerts simulation tablets, they will present that data