58 LAMPIRAN A UJI F KURVA BAKU
Replikasi 1 Konsentrasi
Absorbansi
x2
y2
xy
1,01 3,03 5,05 15,15 25,25 35,35 50,50 65,65 80,80 95,95
0,029 0,031 0,045 0,104 0,159 0,191 0,266 0,350 0,424 0,485
1,0201 9,1809 25,5025 229,5225 637,5625 1249,6225 2550,2500 4309,9225 6528,6400 9206,4025 24747,6260
0,0008 0,0010 0,0020 0,0108 0,0253 0,0365 0,0708 0,1225 0,1798 0,2352 0,6847
0,0293 0,0939 0,2273 1,5756 4,0148 6,7519 13,4330 22,9775 34,2592 46,5358 129,8981
Absorbansi 0,017 0,021 0,024 0,077 0,128 0,176 0,252 0,321 0,391 0,462
x2 1,0201 9,1809 25,5025 229,5225 637,5625 1249,6225 2550,2500 4309,9225 6528,6400 9206,4025 24747,6260
Replikasi 2 Konsentrasi 1,01 3,03 5,05 15,15 25,25 35,35 50,50 65,65 80,80 95,95
58
y2 0,0003 0,0004 0,0006 0,0059 0,0164 0,0310 0,0635 0,1030 0,1529 0,2134 0,5875
xy 0,0172 0,0636 0,1212 1,1666 3,2320 6,2216 12,7260 21,0737 31,5928 44,3289 120,5435
59 Replikasi 3 Konsentrasi 1,01 3,03 5,05 15,15 25,25 35,35 50,50 65,65 80,80 95,95
Replikasi 1 2 3
Absorbansi 0,024 0,034 0,051 0,089 0,142 0,191 0,258 0,338 0,410 0,482
Σx2 24747,6260 24747,6260 24747,6260 74242,8780
x2 1,0201 9,1809 25,5025 229,5225 637,5625 1249,6225 2550,2500 4309,9225 6528,6400 9206,4025 24747,6260
Σxy 129,8981 120,5435 126,6651 377,1067
y2 0,0006 0,0012 0,0026 0,0079 0,0202 0,0365 0,0666 0,1142 0,1681 0,2323 0,6501
Σy2 0,6847 0,5875 0,6501 1,9223
N 10 10 10
Xy 0,0242 0,1030 0,2576 1,3484 3,5855 6,7519 13,0290 22,1897 33,1280 46,2479 126,6651 SSi 0,6794 0,5826 0,6450 1,9070
RDF 9 9 9
Contoh perhitungan: Misal: replikasi 1 SSi = Yc-[(XYc)2 / Xc] = 0,6847-(129,8981/24747,6260) = 0,6794 SSc = ΣYc-[(ΣXYc)2 / ΣXc] = 1,9223-(377,1067/74242,8780) =1,9172 SSp = SSi1+SSi2+SSi3 = 0,6794+0,5826+0,6450 = 1,9070 Fhitung = (SSc-SSp/k-1)/(SSp/12) = (1,9172-1,9070/3-1)/(1,9070/12) = 0,0719 Fhitung = 0,0719 < Ftabel 0,05 (2,27) = 3,35 Karena F hitung < F tabel maka tidak ada perbedaan bermakna antar persamaan regresi.
59
60
LAMPIRAN B HASIL UJI AKURASI DALAM LARUTAN DAPAR FOSFAT ISOTONIS PH 6,8
15,974 19,961 23,947
C Teoritis (ppm) 16,080 20,200 24,000
%Perolehan kembali 99,34 98,82 99,78
0,084 0,104 0,124
16,184 20,381 24,577
16,020 20,200 24,240
101,03 100,89 101,39
0,083 0,105 0,124
15,974 20,171 24,577
16,180 20,280 24,400
98,73 99,46 100,72
Replikasi
%
Abs
C (ppm)
1
80 100 120
0,083 0,102 0,121
2
80 100 120
3
80 100 120
Contoh perhitungan: Dari hasil serapan dimasukkan kedalam persamaan kurva baku terpilih yaitu: y = 0,0069 + 4,7662.10-3x Dimana : y = Serapan x = Konsentrasi teramati Kemudian hitung % perolehan kembali dengan rumus :
60
61 Misal: replikasi 1 pada 80%:
61
62 LAMPIRAN C HASIL UJI PRESISI DALAM LARUTAN DAPAR FOSFAT ISOTONIS PH 6,8
Konsentrasi
100%
Replikasi
Abs
C sampel (ppm)
C teoritis (ppm)
% Perolehan kembali
1
0,102
19,961
20,200
98,82
2
0,104
20,381
20,280
100,50
3
0,104
20,381
20,200
100,89
4
0,103
20,171
20,280
99,46
5
0,102
19,961
20,080
99,41
6
0,105
20,590
20,320
101,33 100,07
SD
0,98
KV
0,97
Contoh perhitungan: Dari hasil serapan dimasukkan kedalam persamaan kurva baku terpilih yaitu: y = 0,0069 + 4,7662.10-3x Dimana : y = Serapan x = Konsentrasi teramati Kemudian hitung % perolehan kembali dengan rumus :
62
63 Misal: replikasi 1 y = 0,0069 + 4,7662.10-3x 0,102 = 0,0069 + 4,7662.10-3x x = 19,961
63
LAMPIRAN D HASIL PENETAPAN KADAR FILM ATENOLOL
Formula
F1
65
F2
F3
F4
Uji
Abs
C (mg/cm2)
1 2 3 1 2 3 1 2 3 1 2 3
0,106 0,108 0,110 0,107 0,110 0,108 0,110 0,109 0,107 0,102 0,104 0,106
1,040 1,061 1,082 1,050 1,082 1,061 1,082 1,071 1,050 0,998 1,019 1,040
C teoritis (mg/cm2) 1,015 1,006 1,022 1,018 1,014 1,020 1,022 1,011 1,023 1,011 1,009 1,017
Kadar (%) 102,490 105,501 105,915 103,178 106,745 103,977 105,915 105,947 102,720 98,686 100,987 102,262
58
KV (%) 104,64 ± 1,87
1,79
104,63 ± 1,87
1,79
104,86 ± 1,85
1,77
100,64 ± 1,81
1,80
Penimbangan (mg) 89,5 88,7 90,1 89,8 89,4 90,0 90,1 89,2 90,2 89,2 89,0 89,7
59 Anova: Single Factor SUMMARY Groups
Count
Sum
Average
Variance
Column 1
3
313,9061
104,6354
3,494745
Column 2
3
313,8995
104,6332
3,503232
Column 3
3
314,5824
104,8608
3,436034
Column 4
3
301,9336
100,6445
3,28468
66
ANOVA Source of
SS
df
MS
F
P-value
F crit
Between Groups
37,28648
3
12,42883
3,62391
0,064521
4,066181
Within Groups
27,43738
8
3,429673
Total
64,72386
11
Variation
59
60 Contoh perhitungan: C(ppm) = (Serapan – a) / b = (0,105 – 0,006863439) / 0,00476615 = 20,590 Nilai a dan b berasal dari perhitungan regresi linear pada hari ke-2. Misal: pada F1 uji 1
67
60
61 LAMPIRAN E HASIL UJI HOMOGENITAS FILM ATENOLOL
Tempat pengambilan F
R
F1
I II III I II III I II III I II III
F2
68 F3
F4
1 Abs 0,106 0,108 0,110 0,107 0,110 0,108 0,110 0,109 0,107 0,102 0,104 1,106
2 C 1,040 1,061 1,082 1,050 1,082 1,061 1,082 1,071 1,050 0,998 1,019 1,040
Abs 0,108 0,107 0,113 0,110 0,113 0,111 0,114 0,110 1,105 0,099 1,101 1,108
C 1,061 1,050 1,113 1,082 1,113 1,092 1,124 1,082 1,030 0,967 0,988 1,061
Abs 0,110 0,110 0,114 0,107 0,114 0,110 0,113 0,107 1,104 0,101 0,103 1,105
Kadar (%)
C teoritis (mg/cm2)
3 C 1,082 1,082 1,124 1,050 1,124 1,082 1,113 1,050 1,019 0,988 1,009 1,030
1,015 1,006 1,022 1,018 1,014 1,020 1,022 1,011 1,023 1,011 1,009 1,017
1 102,46 105,47 105,87 103,19 106,70 104,02 105,87 105,98 102,69 98,72 100,99 102,26
2 104,53 104,42 108,95 106,28 109,81 107,10 109,97 107,02 100,64 95,61 97,87 104,33
KV 3 106,60 107,55 109,97 103,19 110,84 106,08 108,95 103,91 99,61 97,68 99,95 101,23
104,53±2,07 105,81±1,59 108,26±2,14 104,22±1,78 109,12±2,15 105,73±1,57 108,26±2,14 105,64±1,58 100,98±1,57 97,34±1,59 99,61±1,59 102,61±1,58
Keterangan: F = Formula, R = Replikasi, C = Konsentrasi sampel (mg/cm2), Titik 1,2 dan 3 = Pengambilan sediaan pada tiga titik/tempat yang berbeda
61
1,98 1,51 1,97 1,71 1,97 1,49 1,97 1,50 1,55 1,63 1,59 1,54
59 LAMPIRAN F HASIL UJI SWELLING INDEX SEDIAAN FILM ATENOLOL
69
Replikasi I II Formula W1 W2 SI W1 W2 SI W1 (g) (g) (index) (g) (g) (index) (g) F1 0,0447 0,1122 1,510 0,0431 0,1102 1,557 0,0422 F2 0,0392 0,1021 1,605 0,0417 0,1056 1,532 0,0358 F3 0,0655 0,1694 1,586 0,0635 0,1615 1,543 0,0630 F4 0,0761 0,1988 1,613 0,0799 0,2096 1,623 0,0775 Keterangan: W1 = berat awal sediaan; W2 = berat sediaan setelah mengembang
Contoh perhitungan: Misal: F1 pada replikasi 1
59
III W2 (g) 0,1087 0,0936 0,1598 0,2027
SI (index) 1,576 1,615 1,537 1,615
1,548 ± 0,034 1,584 ± 0,045 1,556 ± 0,027 1,617 ± 0,005
LAMPIRAN G HASIL UJI ADHESION TIME SEDIAAN FILM ATENOLOL
Formula
Batch
t (menit)
F1
1 2
209 180
3
227
F2
1 2 3
SD 205,33
23,71
147 169 150
155,33
11,93
F3
1 2 3
360 360 360
360
0
F4
1 2 3
360 360 360
360
0
70
LAMPIRAN H HASIL UJI PELEPASAN SEDIAAN FILM ATENOLOL FORMULA 1
t (jam)
71
0,083 0,17 0,25 0,33 0,417 0,5 1 2 3 4 5 6
Abs 0,075 0,103 0,105 0,118 0,124 0,135 0,197 0,242 0,255 0,277 0,281 0,307
1 Cn' (ppm) 14,296 20,171 20,590 23,318 24,577 26,885 39,893 49,335 52,062 56,678 57,517 62,973
Qt (µg/cm2) 295,935 417,546 426,233 482,695 508,755 556,531 825,813 1021,260 1077,722 1173,274 1190,647 1303,572
Abs 0,065 0,083 0,098 0,100 0,123 0,127 0,174 0,215 0,235 0,274 0,283 0,313
Replikasi 2 Cn' (ppm) 12,198 15,974 19,122 19,541 24,367 25,206 35,067 43,670 47,866 56,049 57,937 64,231
3 Qt (µg/cm2) 252,502 330,681 395,830 404,516 504,411 521,784 725,918 903,992 990,857 1160,244 1199,333 1329,631
58
Abs 0,069 0,076 0,108 0,108 0,116 0,132 0,183 0,233 0,264 0,275 0,301 0,317
Cn' (ppm) 13,037 14,506 21,220 21,220 22,898 26,255 36,956 47,446 53,951 56,259 61,714 65,071
Qt (µg/cm2) 269,875 300,278 439,263 439,263 474,009 543,501 765,007 982,170 1116,811 1164,587 1277,512 1347,004
Qt ratarata
SD
272,771 349,502 420,442 442,158 495,725 540,605 772,246 969,140 1061,797 1166,035 1222,497 1326,736
21,86 60,86 22,29 39,17 18,93 17,55 50,34 59,71 64,47 6,63 47,84 21,86
59 Contoh perhitungan: Misal: Replikasi 1
72
59
60 LAMPIRAN I HASIL UJI PELEPASAN SEDIAAN FILM ATENOLOL FORMULA 2
t (jam)
73
0,083 0,17 0,25 0,33 0,417 0,5 1 2 3 4 5 6
Abs 0,074 0,079 0,113 0,115 0,120 0,131 0,177 0,234 0,275 0,291 0,317 0,362
1 Cn' (ppm) 14,086 15,135 22,269 22,688 23,738 26,045 35,697 47,656 56,259 59,616 65,071 74,512
Qt (µg/cm2) 291,592 313,308 460,979 469,665 491,382 539,158 738,948 986,513 1164,587 1234,079 1347,004 1542,451
Abs 0,054 0,063 0,087 0,092 0,122 0,116 0,171 0,199 0,243 0,273 0,309 0,353
Replikasi 2 Cn' (ppm) 9,890 11,778 16,814 17,863 24,157 22,898 34,438 40,313 49,545 55,839 63,392 72,624
Qt (µg/cm2) 204,726 243,816 348,054 369,770 500,068 474,009 712,888 834,499 1025,603 1155,901 1312,258 1503,362
60
Abs 0,046 0,076 0,076 0,092 0,107 0,126 0,166 0,211 0,258 0,281 0,322 0,359
3 Cn' (ppm) 8,211 14,506 14,506 17,863 21,010 24,996 33,389 42,830 52,692 57,517 66,120 73,883
2
Qt (µg/cm ) 169,980 300,278 300,278 369,770 434,919 517,441 691,172 886,618 1090,752 1190,647 1368,720 1529,421
Qt ratarata
SD
222,099 285,801 369,770 403,069 475,456 510,202 714,336 902,544 1093,647 1193,542 1342,661 1525,078
62,64 36,94 82,52 57,67 35,37 33,17 23,92 77,25 69,54 39,17 28,48 19,90
61 LAMPIRAN J HASIL UJI PELEPASAN SEDIAAN FILM ATENOLOL FORMULA 3
t (jam)
74
0,083 0,17 0,25 0,33 0,417 0,5 1 2 3 4 5 6
Abs 0,046 0,053 0,047 0,050 0,042 0,071 0,089 0,143 0,183 0,208 0,215 0,264
1 Cn' (ppm) 8,211 9,680 8,421 9,051 7,372 13,457 17,233 28,563 36,956 42,201 43,670 53,951
Qt (µg/cm2) 169,980 200,383 174,324 187,353 152,607 278,562 356,741 591,277 765,007 873,589 903,992 1116,811
Abs 0,044 0,038 0,059 0,065 0,079 0,082 0,087 0,183 0,193 0,211 0,229 0,248
Replikasi 2 Cn' (ppm) 7,792 6,533 10,939 12,198 15,135 15,765 16,814 36,956 39,054 42,830 46,607 50,594
Qt (µg/cm2) 161,294 135,234 226,443 252,502 313,308 326,338 348,054 765,007 808,440 886,618 964,797 1047,319
61
Abs 0,050 0,050 0,060 0,064 0,066 0,084 0,108 0,179 0,203 0,209 0,215 0,268
3 Cn' (ppm) 9,051 9,051 11,149 11,988 12,408 16,184 21,220 36,116 41,152 42,411 43,670 54,790
2
Qt (µg/cm ) 187,353 187,353 230,786 248,159 256,846 335,024 439,263 747,634 851,872 877,932 903,992 1134,184
Qt ratarata
SD
172,876 174,324 210,517 229,338 240,920 313,308 381,352 701,306 808,440 879,380 924,260 1099,438
13,27 34,47 31,42 36,42 81,53 30,40 50,34 95,68 43,43 6,63 35,11 45,96
62 LAMPIRAN K HASIL UJI PELEPASAN SEDIAAN FILM ATENOLOL FORMULA 4
t (jam)
75
0,083 0,17 0,25 0,33 0,417 0,5 1 2 3 4 5 6
Abs 0,031 0,051 0,048 0,041 0,050 0,054 0,072 0,132 0,154 0,197 0,208 0,245
1 Cn' (ppm) 5,064 9,260 8,631 7,162 9,051 9,890 13,666 26,255 30,871 39,893 42,201 49,964
Qt (µg/cm2) 104,831 191,697 178,667 148,264 187,353 204,726 282,905 543,501 639,053 825,813 873,589 1034,289
Abs 0,018 0,046 0,044 0,050 0,056 0,075 0,109 0,145 0,175 0,200 0,226 0,258
Replikasi 2 Cn' (ppm) 2,337 8,211 7,792 9,051 10,309 14,296 21,430 28,983 35,277 40,523 45,978 52,692
Qt (µg/cm2) 48,369 169,980 161,294 187,353 213,413 295,935 443,606 599,963 730,261 838,843 951,767 1090,752
62
Abs 0,028 0,040 0,049 0,055 0,083 0,067 0,108 0,157 0,193 0,216 0,220 0,256
3 Cn' (ppm) 4,435 6,952 8,841 10,100 15,974 12,617 21,220 31,501 39,054 43,880 44,719 52,272
2
Qt (µg/cm ) 91,802 143,921 183,010 209,070 330,681 261,189 439,263 652,082 808,440 908,335 925,708 1082,065
Qt ratarata
SD
81,667 168,533 174,324 181,562 243,816 253,950 388,591 598,515 725,918 857,663 917,021 1069,035
29,56 23,92 11,49 30,81 76,35 46,03 91,55 54,31 84,78 44,36 39,81 30,40
LAMPIRAN L HASIL PERHITUNGAN FLUKS TIAP FORMULA
Formula
Batch
Fluks (µg/mL/jam)
F1
1 2 3
161,3 172,6 179,7
171,200
9,28
F2
1 2 3
201,9 204,3 215,3
207,167
7,15
F3
1 2 3
164,2 156,8 157,8
159,600
4,01
F4
1 2 3
156,5 164,9 162,8
161,400
4,37
76
SD
LAMPIRAN M ANALISA DESAIN FAKTORIAL SWELLING INDEX
Response 2 Swelling index ANOVA for selected factorial model Analysis of variance table [Partial sum of squares - Type III] Source
Sum of Squares
df
Mean Square
F
p-value
Value
Prob > F
77
Model
8.925E-003
3
2.975E-003
3.01
0.0943
A-HPMC
1.240E-003
1
1.240E-003
1.26
0.2949
B-PG
7.203E-003
1
7.203E-003
7.29
0.0270
AB
4.813E-004
1
4.813E-004
0.49
0.5048
Pure Error
7.899E-003
8
9.874E-004
Cor Total
0.017
11
Not significant
The Model F-value of 3.01 implies there is a 9.43% chance that a "Model F-Value" this large could occur due to noise. Values of "Prob > F" less than 0.0500 indicate model terms are significant. 58
59 In this case B are significant model terms. Values greater than 0.1000 indicate the model terms are not significant. If there are many insignificant model terms (not counting those required to support hierarchy), model reduction may improve your model.
Final Equation in Terms of Coded Factors: Swelling index
=
+1.58 78
+0.010
*A
+0.024
*B
+6.333E-003
*A*B
59
60 LAMPIRAN N ANALISA DESAIN FAKTORIAL ADHESION TIME
Response 3 Adhesion time ANOVA for selected factorial model Analysis of variance table [Partial sum of squares - Type III] Source
Sum of Squares
df
Mean Square
F
p-value
Value
Prob > F
79
Model
1.006E+005
3
33530.11
190.33
< 0.0001
A-HPMC
96840.33
1
96840.33
549.71
< 0.0001
B-PG
1875.00
1
1875.00
10.64
0.0115
AB
1875.00
1
1875.00
10.64
0.0115
Pure Error
1409.33
8
176.17
Cor Total
1.020E+005
11
significant
The Model F-value of 190.33 implies the model is significant. There is only a 0.01% chance that a "Model F-Value" this large could occur due to noise. 60
61 Values of "Prob > F" less than 0.0500 indicate model terms are significant. In this case A, B, AB are significant model terms. Values greater than 0.1000 indicate the model terms are not significant. If there are many insignificant model terms (not counting those required to support hierarchy), model reduction may improve your model.
Final Equation in Terms of Coded Factors: Adhesion time
=
80
+270.17 +89.83
*A
-12.50
*B
+12.50
*A*B
61
62 LAMPIRAN O ANALISA DESAIN FAKTORIAL PELEPASAN
Response 4 Release ANOVA for selected factorial model Analysis of variance table [Partial sum of squares - Type III] Source
Sum of Squares
df
Mean Square
F
p-value
Value
Prob > F
81
Model
4419.57
3
1473.19
34.36
< 0.0001
A-HPMC
2473.94
1
2473.94
57.71
< 0.0001
B-PG
1073.52
1
1073.52
25.04
0.0010
AB
872.11
1
872.11
20.34
0.0020
Pure Error
342.97
8
42.87
Cor Total
4762.54
11
significant
The Model F-value of 34.36 implies the model is significant. There is only a 0.01% chance that a "Model F-Value" this large could occur due to noise. Values of "Prob > F" less than 0.0500 indicate model terms are significant. 62
63 In this case A, B, AB are significant model terms. Values greater than 0.1000 indicate the model terms are not significant. If there are many insignificant model terms (not counting those required to support hierarchy), model reduction may improve your model.
Final Equation in Terms of Coded Factors: Release
=
+174.82
82
-14.36
*A
+9.46
*B
-8.52
*A*B
63
64 LAMPIRAN P FORMULA OPTIMUM BERDASARKAN METODE DESIGN EXPERT®
83
Solution Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
HPMC
PG
-0.63 -0.33 -1.00 -1.00 -0.60 -0.30 -0.54 -0.73 -0.70 -0.81 -0.75 -0.45 -0.68 -0.78 -0.40 -0.82 -0.52 -0.38
-0.72 0.89 -1.00 1.00 -0.50 0.79 -0.41 0.29 0.88 0.93 0.95 0.32 -0.40 0.27 -0.05 -0.06 -0.48 0.95
Swelling Index 1.55475 1.59251 1.54767 1.584 1.55958 1.59082 1.56183 1.57442 1.58663 1.58586 1.5871 1.57827 1.56106 1.57338 1.57096 1.56659 1.56054 1.59313
Adhesion Time 228.724 225.641 205.333 155.333 226.147 230.229 229.899 198.61 188.889 176.496 182.264 224.114 217.223 194.2 235.152 198.133 232.568 220.041
64
Release
Desirability
173.081 190.482 171.2 207.167 176.189 188.67 176.733 189.825 198.404 201.671 200.562 185.465 178.563 190.362 179.968 185.607 175.625 192.234
1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000
Selected
65
84
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
-0.95 -0.43 -0.38 -0.36 -0.86 -0.83 -0.92 -0.40 -0.45 -0.86 -0.35 -0.45 -0.46 -0.98 -0.43 -0.80
-0.50 0.86 0.80 0.77 -0.09 -0.90 -0.11 0.05 0.19 0.81 0.60 0.10 0.86 -0.78 -0.38 0.95
1.55712 1.59025 1.58989 1.58943 1.56547 1.5502 1.56455 1.57311 1.57555 1.58278 1.58591 1.5735 1.58993 1.5517 1.56333 1.58626
197.125 216.201 222.681 224.219 195.246 216.02 189.776 233.135 226.014 173.98 228.807 227.646 213.332 201.544 237.932 176.676
65
179.681 192.238 190.346 189.77 185.566 171.85 186.191 181.291 183.883 200.851 187.301 182.64 192.904 174.933 176.07 201.815
1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000
LAMPIRAN Q SERTIFIKAT ANALISIS ATENOLOL
85
86 LAMPIRAN R TABEL UJI R
86
LAMPIRAN S TABEL UJI F
87
58
59
88
59
60
89
60
