Application of acoustic emission to the monitoring and end point determination of a high shear granulation process.

The application of a novel monitoring technique, based on the use of acoustic emissions, is reported for a model high shear granulation process. It has been demonstrated that this technique is capable of monitoring changes in physical properties of powder material during granulation (particle size, flow properties and compression properties). The technique is non-invasive, sensitive and relatively inexpensive.

Near-infrared mass median particle size determination of lactose monohydrate, evaluating several chemometric approaches.

The influence of particle size on near-infra red (NIR) spectra is typically considered a 'nuisance factor' which many scatter correction methods attempt to eliminate, e.g., multiplicative scatter correction. However, particle size is a key issue in the formulation of many pharmaceutical products and has a profound effect on the behaviour of both raw materials and drug substances during formulation. NIR has already been demonstrated as a potential alternative particle sizing technique to current accepted methodology. This investigation assessed several chemometric approaches that model this information, using lactose monohydrate as the raw material. A variety of modelling techniques were applied to both zero order and second derivative spectra namely multiple linear regression, partial least squares, principal component regression and artificial neural networks. One further data transformation evaluated was polar coordinates, although no statistical data were generated. Typically, cross-validation root mean square errors of calibration and cross-validation root mean square errors of prediction of approximately 5 microns were calculated for all of the modelling techniques. These values are comparable to those associated with the reference technique (laser diffractometry). Correlation coefficients of approximately 0.98 for all techniques were also calculated. The predictive abilities for models generated using second derivative spectra were found to be comparable to those obtained using zero order spectra.

Application of chemometric experimental designs in capillary electrophoresis: a review.

Various chemometric experimental designs have been employed for the optimisation of capillary electrophoresis (CE) methods. Similar designs have been utilised in the assessment of the robustness of CE methods. The designs employed include central composites, fractional factorials, Plackett-Burman, simplex and overlapping-resolution mapping. Optimisation studies have largely concentrated on the use of these designs on selection of the optimal electrolyte composition. The robustness testing studies performed have involved the use of screening designs to identify the critical parameters affecting responses such as migration times and resolution. Further designs such as central composites have then been employed to set method limits following robustness studies. It is concluded that the use of experimental designs and statistical data evaluation in conjunction with personal computer-controlled CE autosamplers and instruments are of great benefit in the optimisation and robustness evaluation of CE methods.

Validated capillary electrophoresis method for the assay of a range of basic drugs.

A capillary electrophoresis method has been developed and validated for the analysis of a wide range of basic drugs. Acceptable precision was obtained by employing an internal standard. Optimal sensitivity was obtained using low UV wavelengths. An experimentally designed study showed the method to be robust. The method has advantages over HPLC in terms of simplicity, speed and cost. The method is now in routine use for identity confirmation and assay of both drug substance and formulations.