Validity of particle size analysis techniques for measurement of the attrition that occurs during vacuum agitated powder drying of needle-shaped particles.

Analysis of needle-shaped particles of cellobiose octaacetate (COA) obtained from vacuum agitated drying experiments was performed using three particle size analysis techniques: laser diffraction (LD), focused beam reflectance measurements (FBRM) and dynamic image analysis. Comparative measurements were also made for various size fractions of granular particles of microcrystalline cellulose. The study demonstrated that the light scattering particle size methods (LD and FBRM) can be used qualitatively to study the attrition that occurs during drying of needle-shaped particles, however, for full quantitative analysis, image analysis is required. The algorithm used in analysis of LD data assumes the scattering particles are spherical regardless of the actual shape of the particles under evaluation. FBRM measures a chord length distribution (CLD) rather than the particle size distribution (PSD), which in the case of needles is weighted towards the needle width rather than their length. Dynamic image analysis allowed evaluation of the particles based on attributes of the needles such as length (e.g. the maximum Feret diameter) or width (e.g. the minimum Feret diameter) and as such, was the most informative of the techniques for the analysis of attrition that occurred during drying.

Studies of particle drying using non-invasive Raman spectrometry and particle size analysis.

The evaporation of methanol from needle-shaped particles of cellobiose octaacetate (COA) has been studied directly in a jacketed vacuum drier using in situ measurements by Raman spectrometry. A design of experiments (DoE) approach was used to investigate the effects of three parameters (method of agitation, % solvent loss on drying and jacket temperature), with the intention of minimising the drying time and extent of particle attrition. Drying curves based on Raman signals for methanol and COA in the spectra of the wet particles indicated the end of drying and revealed three stages in the drying process that could be used to monitor the progress of solvent removal in real time. Off-line particle size measurements based on laser diffraction were made to obtain information on the extent of attrition, to compare with the trends revealed by the Raman drying curves. The study demonstrated that non-invasive Raman spectrometry can be used to study the progress of drying during agitation of particles in a vacuum drier, allowing optimisation of operating conditions to minimise attrition and reduce drying times. Although a correlation between particle size and off-line Raman measurements of COA was demonstrated, it was not possible to derive equivalent information from the in situ Raman spectra owing to the greater effects of particle motion or bulk density variations of the particles in the drier.