New Technologies - APV

Micronised APIs in direct compression
aggregation of API particles predominates over binding to the carrier surface.
This is not a surprising observation which can be applied to allexcipients.
However, Figure 2 shows that there are also differences in the uniformity
of the mixtures obtained with the different carriers for a given API.
The best homogeneity for both APIs was found for the excipient with the
highest surface area (Parteck® M, Table 1). This indicates a correlation
between BET surface area and/or pore volume and the achievable homogeneity.
However, there are also significant differences between spray-dried
and granulated DC-mannitol although they have similar BET-surfaces (Fig 7).
So, both the quality of the surface structure and the quantitative size of the
surface area seem to be relevant.
Figure 2: Relative standard deviations of the API concentration in
samples containing a model API and different DC-mannitols as
excipients.
To test the strength of the adsorption of API to the excipient surface the
remaining concentration of ascorbic acid and riboflavin was measured after
15 min on an air jet sieve. In this set-up, fine API particles that were not
strongly adsorbed would be lost. A recovery of 100% would mean complete
adsorption of the API to the carrier while a recovery of 0% would indicate
no absorption to the carrier.
Figure 3: Comparison of the API concentration measured after
15 min in an air jet sieve using either granulated DC-Mannitol B,
spray-dried DC-Mannitol A or Parteck® M as excipient for model
drugs ascorbic acid or riboflavin.
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A much stronger adsorption was found for the spray-dried DC-mannitols
compared with the granulated quality (Fig. 3). For low API concentrations of
a hydrophilic drug, the two spray-dried mannitols showed similar results.
Using higher API loads, it was demonstrated that the higher surface area of
Parteck® M showed a higher binding capacity. This effect was confirmed
with a hydrophobic API, riboflavin. These results may again be explained by
the different surface structure of the investigated excipients. The lower
recovery of the hydrophobic API again confirms a weaker surface adsorption
of this class of API.
Figure 4: SEM image showing a mixture of Parteck® M 200 and
micronized ascorbic acid (drug load 1% w/w).
Figure 5: SEM image showing a mixture of spray dried DC-
Mannitol A and micronized ascorbic acid (drug load 1% w/w).
To visualize the API distribution on the carrier surface, SEM was employed.
Figure 4 shows the SEM image of a mixture of ascorbic acid and Parteck® M.
The micronized API particles are readily identifiable due to the different
crystal structures of API and carrier (coloration performed manually). The
API crystals were found within the pore structure of the much larger excipient
particles. Figure 5 shows the SEM image of spray-dried DC-Mannitol A