This thesis presents a detailed study into the role of surface chemistry in the high shear
granulation of organic pharmaceutical solids. Crystalline materials with markedly different
surface chemistries were selected as model compounds which were granulated with a
polymeric binder.
The surface wettability of primary powders was evaluated by employing the sessile drop
contact angle measurements to evaluate the facet-specific surface energetics of
macroscopic crystals, obtained via a solvent-mediated or a temperature-controlled
crystallisation technique. A novel methodology using inverse gas chromatography (IGC) at
finite concentrations (FC) was developed to evaluate surface energy distributions of the
powder samples.
The surface energetics of organic macroscopic crystals was found to be facet-specific,
consistent with the local surface chemistry of the facet under examination. The rank order
of hydrophilicity of specific facet was in good agreement with concentration of hydroxyl
groups determined from X-ray photoelectron spectroscopy. IGC-FC was applied to
measure [gamma]d/SV profile, which were in good agreement with the [gamma]d/SV values measured from
contact angle on the corresponding single crystals. This technique was shown to be able to
distinguish surface energy heterogeneity, homogeneity as well as subtle changes in the [gamma]d/SV distributions, due to variations in the crystal habits. The wettability of the model
compounds was ranked based on the contact angle polarity and IGC surface energy
heterogeneity distributions, and the spreadability of binder solution was assessed based on
the thermodynamic spreading coefficients. The increase in surface wettability led to the
increase in granule mean size and granule strength. Formulations with similar wetting
behaviour resulted in similar granule size, whilst those formulations with dissimilar surface
wettability were found to exhibit substantially different granulation behaviour.
In conclusion, the materials surface chemistry plays a crucial role in granulation processes.
Its thorough characterisation and understanding may lead to more controllable product
attributes and improved final performances.