TECHNICAL

INFORMATION

Matrix Effects on the Performance of Disintegrants (I) –

Hydrophobic Tablets

VIVAPUR® MCC (Insoluble Binder) 17 or 20 %

Abstract
EMCOMPRESS® DCP (Insoluble Filler) 68 %

Superdisintegrants are categorized by their mechanism of action LUBRITAB , Hydrogenated Cottonseed Oil
®
10 %
(Hydrophobic Model Compound)
such as wicking, swelling or shape recovery. In this study, the
PRUV ® SSF (Lubricant) 1%
performance of disintegrants from each of these groups was
tested in an insoluble, hydrophobic tablet formulation. Disintegrants 1 or 4 %
VIVASOL® CCS
The matrix' hydrophobicity led to strong deviations from the
EXPLOTAB® SSG
expected behaviors for insoluble tablets without distinct hydro- VIVAPHARM® PVPP XL
phobicity. It is noteworthy that the differences only became ob- Tab. 1 Tablet Matrix
vious at sub-optimal, low dosage of the superdisintegrants.
At the recommended standard use level, all formulations showed
rapid disintegration.

Introduction Results

Recommendations for the selection of disintegrants are usually As a first step, the disintegrants were incorporated at a commonly
based on the solubility of the tablet matrix and the active ingre- used level of 4 %. The resulting disintegration times were recorded
dient. Wicking disintegrants, such as croscarmellose sodium in the format shown in Table 2.
(CCS), are commonly recommended for soluble matrices.
Disintegration Times in seconds
Wicking enables fast distribution of water throughout the tablet
20 21 46 55 68
Compaction

matrix, thus leading to rapid dissolution of the soluble matrix

Force [kN]

15 27 38 40 57
components. Sodium starch glycolate (SSG) and other swelling-
10 19 32 53 40
type disintegrants are often selected for insoluble matrices.
5 19 28 17 36
In this case, the swelling potential of the disintegrant is utilized to 1 7 14 28
mechanically disrupt the structure of the tablet. Crospovidone Storage Duration [days]
Tab. 2 Format for Data Collection
(PVPP) is considered a universally suitable disintegrant, exhibiting
a combination of the three mechanisms mentioned above.
In addition to being insoluble, certain APIs may display a high de- Figure 1 summarizes the findings of the 4 % trials for all disinte-
gree of hydrophobicity, thus affecting the wettability of the entire grants and media used.
tablet. The aim of this study was to investigate into the effect of Irrespective of the type of superdisintegrant and test medium,
matrix hydrophobicity on the performance of different types of all disintegration times remained under 120 seconds.
superdisintegrants. In order to obtain a clearer picture of the potential differences,
more discriminating conditions were created by reducing the
superdisintegrant level to 1 %.
Materials and Methods Figure 2 displays the corresponding results. As opposed to the
first set of experiments, clear trends now became apparent:
The composition of the test matrix is shown in Table 1.
LUBRITAB® (hydrogenated cotton-seed oil) was used as a highly
hydrophobic model compound. VIVASOL® CCS, EXPLOTAB® SSG,
• Interestingly, VIVASOL® CCS remained almost unaffected by
and VIVAPHARM® PVPP XL were used as superdisintegrants. compaction force, storage duration and media pH.
PRUV ® sodium stearyl fumarate (SSF) served as a lubricant.
• EXPLOTAB® SSG, by contrast, showed slightly increased
• Tablets were compressed at four different compaction forces disintegration times in pH 1 upon storage.
and stored for 1,7,14, and 28 days at 40°C/75 % r.h. prior to
testing the disintegration time. Water as well as pH 1 and pH • VIVAPHARM® PVPP at 1 % exhibited prolonged disintegration
in all media.
6.8 buffers were used for disintegration testing.

www.jrspharma.com 01
 TECHNICAL
INFORMATION

Results & Discussion

Water HCI Buffer

VIVASOL® 4 % Water VIVASOL® 4 % HCI VIVASOL® 4 % Buffer
20 21 46 55 68 20 18 29 48 58 20 20 32 51 97
15 27 38 40 57 15 17 24 35 54 15 15 24 36 55
10
5
19
19
32
28
53
17
40
36
10
5
16
17
19
14
37
33
36
38
10
5
17
15
20
21
36
26
41
49
CCS
1 7 14 28 1 7 14 28 1 7 14 28

EXPLOTAB® 4 % Water EXPLOTAB® 4 % HCI EXPLOTAB® 4 % Buffer

20 26 33 53 64 20 22 25 58 109 20 21 33 49 63
15 19 28 43 64 15 19 30 47 74 15 18 31 48 54
10
5
18
19
22
16
41
35
41
32
10
5
14
15
28
19
34
32
54
34
10
5
19
18
24
20
40
31
40
32
SSG
1 7 14 28 1 14 28 1 7 14 28

VIVAPHARM® PVPP XL 4 % Water VIVAPHARM® PVPP XL 4 % HCI VIVAPHARM® PVPP XL 4 % Buffer

20 36 32 61 107 20 28 66 53 118 20 28 57 51 112
15 35 35 64 129 15 27 38 50 120 15 24 42 54 125
10
5
30
23
45
34
68
58
102
94
10
5
27
26
32
32
56
45
124
83
10
5
27
22
35
34
49
54
104
87
PVPP
1 7 14 28 1 7 14 28 1 7 14 28

Fig. 1 Disintegration Times for 4 % Disintegrant Concentration

15 s 150 s 2000 s

Water HCI Buffer

VIVASOL® 1 % Water VIVASOL® 1 % HCI VIVASOL® 1 % Buffer
20 20 48 67 105 20 48 68 93 139 20 35 56 116 88
15 23 40 65 71 15 37 54 78 135 15 23 42 67 78
10
5
26
23
36
30
104
67
57
43
10
5
31
20
44
38
56
35
105
68
10
5
21
19
37
30
47
37
56
58
CCS
1 7 14 28 1 7 14 28 1 7 14 28

EXPLOTAB® 1 % Water EXPLOTAB® 1 % HCI EXPLOTAB® 1 % Buffer

20 35 56 95 138 20 39 114 172 311 20 27 76 110 104
15 30 36 59 147 15 25 90 158 269 15 26 52 55 78
10
5
27
22
33
25
53
38
72
53
10
5
39
23
97
58
121
67
218
139
10
5
23
16
39
33
50
39
75
67
SSG
1 7 14 28 1 7 14 28 1 7 14 28

VIVAPHARM® PVPP XL 1 % Water VIVAPHARM® PVPP XL 1 % HCI VIVAPHARM® PVPP XL 1 % Buffer

20 275 151 445 1096 20 319 245 505 1589 20 137 151 464 1357
15 170 165 473 1422 15 212 247 492 1923 15 115 145 526 715
10 86 140
113
349 640
512
10 145
56
238
164
536
276
1216 10 83 132 372 497
297
PVPP
5 59 247 5 494 5 47 99 221
1 7 14 28 1 7 14 28 1 7 14 28

Fig. 2 Disintegration Times for 1 % Disintegrant Concentration

15 s 150 s 2000 s

www.jrspharma.com 02
Discussion Summary

Superdisintegrants do not follow a sole mechanism, but rather The expected behaviors of the three super-disintegrants in an
show a mix of the three main behaviors, namely wicking, swelling insoluble matrix would have suggested the following ranking of
and shape recovery. Nonetheless, each type of super-disintegrant suitability: SSG>PVPP>CCS.
has its prevailing mechanism. For PVPP, the disintegration action In addition, a loss in efficiency was expected for SSG and CCS
is mainly based on a fast, but relatively short-ranged shape reco- at low pH. The actually observed ranking, however, was
very. It exhibits only moderate swelling and wicking. In case of CCS>SSG>PVPP. Only SSG lost some activity at pH 1, whereas
the hydrophobic, plastically deforming test matrix, 1 % of PVPP CCS maintained its disintegration power.
was apparently not sufficient for rapid disintegration because of
low water ingress and because of the plastic matrix yielding to
the short-range expansion of the superdisintegrant. CCS and SSG
both possess carboxyl groups, which lose part of their water bin-
ding capacity at low pH. Reduced water binding leads to reduced
Conclusion
swelling. Hence, SSG is less efficient at pH 1 than in water or at
pH 6.8 respectively. Wicking, being CCS's predominant mecha-
At the recommended use level of 4 %, all superdisintegrants
nism is less affected by pH, as shown in Graph 1.
tested showed very fast disintegration in all test media.
The tablets' hydrophobicity presented an obstacle to fast water
penetration of the tablets. The water-dependent swelling of SSG
7
could therefore not be fully utilized.
The strong wicking effect of CCS helped to overcome the tablets'
6
hydrophobicity and therefore enabled rapid and pH-independent
Liquid Update [g]

5
disintegration.
4 The study demonstrated, that not only matrix solubility but also its
3 affinity to water should be considered for disintegrant selection.
EXPLOTAB® SSG Water
2 EXPLOTAB® SSG HCI For very hydrophobic tablets, wicking disintegrants, such as
1
VIVASOL® CSS Water VIVASOL® CCS, appear to be the best choice.
VIVASOL® CSS HCI
0
For further information on disintegration mechanism, please
0
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
320
340
360
380
400
420
440
460
480
500
520
540
560
580
600

refer to our Technical Information “The Effect of Humidity on

Time [s]
Tablet Surfaces Containing Different Types of Superdisintegrants”.
Graph 1 Medium Uptake of Disintegrant Powder (100 %)

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Disclaimer:
The information provided in this brochure is based on thorough research and is
believed to be completely reliable. Application suggestions are given to assist our
customers, but are for guidance only. Circumstances in which our material is used
vary and are beyond our control. Therefore, we cannot assume any responsibility
for risks or liabilities, which may result from the use of this technical advice.

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