T ABLET PREPARATION FOR THE SCREENING OF THE EFFICIENCY OF DIFFERENT

Mannitol based orally disintegrating tablets were prepared using three levels of superdisintegrants (3, 5, 7% w/w) in order to compare the efficiency of crospovidone, croscarmellose sodium and sodium starch glycolate. Similar tableting fill volumes were used, which improved the comparability of the formulations. Two tableting pressures were applied to tablets, since the tablet porosity and the degree of compaction could influence the behaviour of the superdisintegrants (Goel et al., 2010).

Table 11 Physical characteristics of various tablets containing different superdisintegrants^a

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Tablet hardness, wetting time and in vitro disintegration time are in vitro parameters of tablets, which are often used for the characterisation of ODTs (Shukla et al., 2009b).

These parameters are useful for comparing the superdisintegrants and they can provide information about the best superdisintegrant, its amount and the optimum tablet hardness. Parameters of different formulations can be seen in Table 11. Two tableting pressure level, high (H) and low (L) were applied in the case of each formulation, and the superdisintegrant content also varied. Friability values of the tablets were below the 1% level in all cases.

Crospovidone (CrosP) was the Kollidon^® CL-SF type, which decreased the bulk density of the powder mixture, therefore mechanical hardness and the weight of the tablets were lower in the case of these formulations. Hardness of the tablets decreased using higher levels of croscarmellose sodium (CCS) at the low pressure level, but tablet hardness was not influenced using sodium starch glycolate (SSG). It can be concluded that SSG had smaller influence on the characteristic of the powder mixture and did not affect negatively the bonds between the excipient particles and was able to provide the most robust formulation from a technological point of view.

The in vitro disintegration time of tablets was influenced by neither the CrosP concentration nor the applied pressure level. Crospovidones are characterised by high specific surface area and low bulk density (Nakanishi et al., 2011) and the Kollidon^® CL-SF (Fig. 16) is an especially “light” powder. Presumably, it created a superdisintegrant network around the particles and allowed the fast wetting of the tablet.

On the other hand, it might prevent the strong cohesive bonds between the filler particles due to its high specific surface area, therefore the wetted tablet disintegrated fast irrespective of the actual hardness value.

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Figure 16 SEM picture of crospovidone (Kollidon^® CL-SF) at magnification of 2000×

There was a correlation between the tablet hardness and the disintegration time in the case of formulations that contained SSG (Fig. 17). There was a trend of lower wetting and disintegration times using higher levels of the excipient in spite of the similar mechanical strengths, which indicated that a higher amount of this excipient was necessary for effective disintegration.

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Figure 17 SEM picture of sodium starch glycolate (Explotab^®) at magnification of 500×

Disintegration and wetting times were the lowest at 3% w/w of CCS (Fig. 18) and significantly faster wetting was achieved using the higher pressure level, which could be surprising at the first glance. Considering that one of the main disintegrating effects of CCS is particle twisting (Thibert and Hancock, 1996), it is obvious that this excipient works better in a low porosity environment. Wetting times were also smaller in the case of tablets prepared with high pressure, which indicated that primarily CCS particles being in close contact could cause the water wicking not the tablet porosity itself.

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Figure 18 SEM picture of croscarmellose sodium (Vivasol^®) at magnification of 500×

Consistency index is a numerical value between 1 and 10, which refers to the solidity of the tablet mass after complete wetting (Fig. 10/4). Wetting time is only meaningful if this value is also supplied, since a wetted but hardly disintegrated tablet cannot disintegrate fast in the mouth. It can be seen that tablets that contained CrosP and were prepared with high pressure had lower consistency index in all cases, which can be associated with the higher wetting times and the mechanism of effect of CrosP. Tablets containing 7% CrosP had the lowest wetting time but the highest consistency index, which might be due to the good water binding and poor swelling ability of the excipient (Thibert and Hancock, 1996). The net of the CrosP particles imbibed significant amounts of water but the mannitol matrix did not wetted properly, therefore the filler matrix did not dissolve to cause disintegration. The consistency indices of tablets containing SSG were low but this effect was not associated with the good disintegration action of the excipient rather with the slow wetting that enabled the dissolution of the mannitol particles. On the other hand, SSG has also good swelling properties (Thibert and Hancock, 1996), which could also contribute to the mechanical weakening effect of this excipient. CCS was the best superdisintegrant with water soluble filler. It provided fast wetting and low consistency index using the high pressure level, i.e. it had both good water wicking and disintegrating effect. It was more effective at lower

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concentrations in vitro, which might indicate that above a threshold value the excipient had inhibiting effect on the disintegration. Since these excipients are water insoluble cross-linked polymers, they could form viscous suspension at higher concentrations which could be the explanation of their concentration dependent disintegration effects.

6.3. Tablet preparation based on the swelling of crospovidone and the phase