Ingela Niklasson Björn

In situ monitoring and control of moisture content in pharmaceutical powder processes using an open-ended coaxial probe

An analysis of microwave measurements of the complex dielectric constant of different mixtures of pharmaceutical materials using an open-ended coaxial probe is presented. Using the probe in combination with a network analyser, measurements in the frequency range of 1–19 GHz were conducted. Calibration measurements on conditioned samples were first acquired in a controlled laboratory environment, and then in situ measurements, taken in a small-scale high-shear mixer, were also obtained. The dominating material in the investigated mixtures was microcrystalline cellulose. By using the suggested microwave method, a novel possibility for in situ measurements of the initial moisture content of the powder mixture before and at the beginning of the water addition stage is demonstrated. In situ density-independent estimation of the moisture content having a relative error of below 10% for the moisture interval of 2–14% is demonstrated. The possibility of performing an adaptive control of the evolution of the mixing process by utilizing the microwave sensor information is also presented.

Mechanistic time scales in adhesive mixing investigated by dry particle sizing

This study exploits the mechanisms governing blending of adhesive mixtures, i.e. random mixing, de-agglomeration and adhesion, and their relative importance to achieve mixing homogeneity. To this end, blending of micronized particles (fines) with carrier particles was carried out using a high shear mixer. Dry particle sizing using laser diffraction coupled with a strong powder dispersion unit was employed to measure the fines content in samples collected during mixing, and hence to assess blend homogeneity. The method was also employed to evaluate the relative strength of the agglomerates present in the fines. Particle sizing using a non-destructive imaging technique was used to monitor changes in particle size during blending. It could be shown that the de-agglomeration of the fine-particle agglomerates is the slowest mechanism and hence the rate-limiting step as regards achieving a homogeneous adhesive mixture. Consequently, a longer mixing time is needed for blending of larger agglomerates. Being fast, simple and reproducible, the laser diffraction technique was shown to be an efficient method for measurement of fine particle content and homogeneity of a mixture, while the non-destructive image analysis was able to give relevant information on the rate of de-agglomeration of the fine-particle agglomerates as well as on the size of the resulting carrier-fine particle assemblies.

Multivariate analysis for product design and control

Abstract Fluidised bed coating of pellets, granules or particles plays a very important role in the development and production of oral controlled release formulations. Based on design of experiments for robustness testing of the manufacturing process, a 24−1 fractional factorial was planned. During the experiments in-line NIR spectroscopy was combined with a theoretical film growth model in order to monitor and control the coating process. The increase in film thickness during the process evolvement was calculated and compared with the film thickness obtained by a reference method off-line, image analysis. NIR spectra were aquired during coating by means of a fiber optic probe positioned in the fluid bed. Time series of NIR spectra were calibrated with the corresponding theoretical film thickness by a multivariate analysis method, PLS (partial least square) regression. Film thickness predicted by the PLS model was then compared with the actual median thickness, as measured by image analysis off-line. The calibration of in-line NIR-spectra to film thickness calculated with a growth model is successful with PLS. The PLS model contains three principal components, which describe 99% of the variance in NIR-spectra and the variation in film thickness calculated by the growth model. The root mean square error (RMSE) between the film thickness predicted by NIR-spectra and the film thickness calculated by the theoretical growth model is 1.2 μm.

Towards quantitative prediction of the performance of dry powder inhalers by multi-scale simulations and experiments

Graphical abstract Figure. No caption available. ABSTRACT This work demonstrates the use of multi‐scale simulations coupled with experiments to build a quantitative prediction tool for the performance of adhesive mixtures in a dry powder inhaler (DPI). Using discrete element model (DEM), the behaviour of fine‐carrier particle assemblies upon different mechanisms encountered during dose entrainment and dispersion can be described at the individual particle level. Combining these results with computational fluid dynamics (CFD) simulations, the complete dosing event from a DPI can be captured and key performance measures can be extracted. A concept of apparent surface energy, ASE, was introduced to overcome challenges associated with the complex particle properties, e.g. irregular particle shapes and surface roughness. This approach correctly predicts trends observed experimentally regarding API adhesivity, flow rate and device geometry. By incorporating the effects of drug load, critical adhesion and surface energy distributions to the simulation tool, the fine particle fraction could be predicted with good agreement to experiments for two different formulations in two different devices at two flow rates. It is concluded that multi‐scale simulations provide a useful tool to support device and formulation development, as well as to gain further insight into the physical mechanisms governing dispersion from DPIs.

Diabatic distillation—Comments on the influence of side streams

Abstract In diabatic distillation the internal flows of vapour and liquid vary along the column and in the design calculations of such columns the diameter of the column has been allowed to change accordingly. However, if the column is fixed the variations in internal flows will influence the performance of the trays and thus the efficiency and separation. The configuration studied was based on a distillation pilot plant and compared with the simulations in PROII. The column used was a tray column with 12 sieve trays with 20 cm inner diameter and 6 m height. In this study simulations were made to include the effect of changing tray efficiencies due to varying internal flow and to see its influence on the separation and other measures of performance. It was found that under certain diabatic conditions the tray efficiencies changed in favour of an increased total separation and including also improved thermodynamic efficiency. A comparison was made between experimentally and theoretically (based on the Chan & Fair model) determined tray efficiencies. Both experimental and simulation results showed the same trend but with a slight difference.