ODT Disintegration

Figure 3.10 shows a graph of the mean disintegration times of three ODT’s tested for each grade of

mannitol, compared to milled mannitol (F2). From the results it was observed that the spray dried

grades, Mannogem EZ and Pearlitol 200SD, produced ODTs with fast disintegration time. Upon

statistical analysis it was also seen that the spray dried grades were significantly better disintegrating

than both the crystalline powders and granulated forms of mannitol tested. This was because the

spray dried powders had a fairly small particle size of between 150-200 μm as well as pores on the

surface as seen in SEM images which may have helped increase the water uptake into the ODT, leading

to faster disintegration. At 75 MPa the crystalline powders also had relatively low disintegration times

of around 50 seconds, which wasn’t statistically different from the spray dried grades, however there

was a big increase in disintegration time at 225 MPa compared to the spray dried grades. At 75 MPa

the ODTs composed of the crystalline powder disintegrated quite quickly as it had a relatively small

particle size which allowed wetting of the tablet, and as the hardness was fairly low, water was able

to penetrate the tablet structure more rapidly, allowing a fast disintegration of the ODT. At 225 MPa

there would have been significant fragmentation occurring in the crystalline powder tablet, and as

hardness was high, the subsequent disintegration time of the tablet was also high. However the

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granulated forms had a significantly higher disintegration time than all the other commercial grades,

and at 225 MPa the disintegration time was only significantly higher when compared to the spray

dried forms, with the crystalline form having similar times at this compaction force. The high

disintegration time of the granulated powders may have been due to the large particle size of the

mannitol, the highest disintegration time observed was with the Pearlitol 500DC which had the largest

mean size of particle, which in turn led to a slower disintegration time as the large particles took longer

to break down within the disintegration medium (S Velmurugan and Vinushitha, 2010). This would

have been due to the agglomeration of the mannitol crystals into one large particle, which would have

resulted in large particles with the absence of pores, meaning it would have been more difficult for

water to penetrate the particle and allow subsequent disintegration. Both Mannogem grades also

displayed long disintegration times due to the very large particles present within the powder.

0 50 100 150 200 250 300 350 400 F2 Mannogem Powder Mannogem 2080 Mannogem Granular Mannogem EZ Pearlitol 50C Pearlitol 500DC Pearlitol 200SD Dis in tegratio n time (s ) Powder 75MPa 225MPa

Figure 3.10: A graph showing the disintegration times of the commercial mannitol grades compared to the

milled mannitol. The results clearly show that milled mannitol provides advantages for tablet disintegration with the milled mannitol being significantly better than all grades at both compaction forces (except for the Mannogem Powder and Pearlitol 50C at 75 MPa. Data is presented as mean ± SD (n=3, p<0.05).

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The clear advantage of milled mannitol compared to the commercial grades was its improved

disintegration time. Statistical analysis showed that disintegration times with the milled mannitol was

significantly lower than all the commercial grades at the 225 MPa compaction force, and all

commercial grades at 75 MPa, except the crystalline powders (Mannogem powder and Pearlitol 50C).

The poor disintegrating qualities of the granulated grades was due to the very large sized

agglomerated particles, which led to significantly longer disintegration. Although the spray dried

grades presented advantages in terms of disintegration compared to the granules, possibly due to the

spherical smaller sized particles which contained pores, the milled mannitol was still clearly

advantageous. This was due to the very small particle size of the milled powders (approximately 11

μm) and increased wettability of the mannitol crystal. This increased wettability of the powder

particles was due to a higher exposure of the (011) plane, established as the most hydrophilic plane

on the mannitol crystal, which led to an improved wetting of the ODT and therefore a faster

disintegration of the dosage form (Koner et al., 2015).

Table 3.2 shows the porosities of the ODT’s manufactured from the different grades of mannitol tested

in this study. Statistical analysis showed that at 75 MPa, the milled mannitol was more porous than

the commercial grades, which also gave further evidence for the faster disintegration of the ODTs. The

spray dried form was expected to be more porous than the granulated grades as there were visible

pores within the particles on the SEM monographs obtained, with significant pores visible on the

Mannogem EZ (Figure 3.1 (E)). It can be said that the porosity differences between the graded

mannitol was negligible, with all powders displaying a high porosity. The high porosity of the crystalline

powder was due to the fragmentation of the needle shaped particles which led to a more porous

structure, and it was seen that the Pearlitol 50C did have a slightly higher porosity than Mannogem

powder due to more profound needle shaped crystals present within the powder blend. The

granulated forms also formed highly porous ODT’s as the large particles were unable to fill in the voids

between the individual particles during packing resulting in more open pores within the tablet

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However the F2 milled powder tended to show a lower porosity at 225 MPa compared to all of the

grades of mannitol tested in this study. This was due to the fact that the milled powders contained

very small particles, which when poured into the die before compaction, and during rearrangement

within the dies, could fill any small spaces of air and allow a more solid compact to be formed with a

less porous structure. Compared to the 75 MPa ODTs, where the compaction force wasn’t high enough

to force the small voids to be filled, the 225 MPa tablets presented a less porous structure than the

commercial grades. However, for milled mannitol, disintegration of the ODTs at 225 MPa was

massively improved compared to the commercial grades, largely due to the increased hydrophilicity

and wettability of the dosage forms.

3.4 Conclusion

In conclusion it can be seen that the spray dried mannitol had the best mechanical properties for

utilisation as a binder within ODT tablets. This study indicated that it forms ODT’s that have very high

hardness and low friability, whilst also giving the lowest overall disintegration times of all the

commercial brands tested. This was due to the presence of the alpha polymorph within the powder,

which, as previously shown in literature, had the highest compressibility of all the mannitol

polymorphs. The granulated forms however didn’t display any significant improvements in tablet

properties. This was due to the lack of α-mannitol present within the powder. The granulated forms

did display a significant improvement in flow which is a key component for tabletting. If the excipient

flows well it will promote the uniform flow of the bulk powder blend into the dies before compression,

which is the key advantage of using granulated mannitol as opposed to the crystalline mannitol

powder.

The key advantage of the milled mannitol was its very low disintegration time due to the increased

wettability of the powder, providing ODTs that disintegrated rapidly, much faster than any of the

commercial grades. Although mechanical strength and the friability of the milled mannitol ODT’s was

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difference and upgrade compared to the commercial powders. The main disadvantage of the milled

powders was the flowability which was very, very poor. As mentioned above, good powder flow is key

in tableting to allow homogenous bulk powder movement into the dies, which produces a uniform

and reproducible tablet. The flowability of the milled mannitol, as seen in the previous chapter, was

capable of being enhanced to suitable levels, and therefore the milling of mannitol provided a suitable

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