Scaling up the spray drying process from pilot to production scale using an atomized droplet size criterion.

PURPOSE: The purpose of this study was to investigate the possibility of producing identical powders in pilot and production scale spray drying equipment by matching the droplet size distributions produced by two differently sized atomizers. METHODS: Particles were prepared by spray drying solutions of acetaminophen and polyvinylpyrrolidone K-30. The success of the up-scaling was evaluated by comparing the powders in terms of particle size distribution (laser diffraction), crystallinity (XPRD) and morphology (SEM). Furthermore, the influence of process parameters on other product characteristics such as stability and residual volatile content was also evaluated. RESULTS: The spray drying experiments resulted in spherical, amorphous particles with volumetric median diameters of typically 4-10 microm for pilot scale and 4-30 microm for production scale. The results showed that particles with similar morphology and crystallinity could be produced in the two applied spray dryers. However, scale-up based purely on matching droplet size distributions was not feasible. CONCLUSIONS: The scale-up criterion did not account for the differences between the droplet-drying gas mixing and residence time distribution within the two spray dryers. Therefore, production scale experiments are required in order to obtain similar product characteristics as in pilot scale.

Flow reversal at low voltage and low frequency in a microfabricated ac electrokinetic pump.

Microfluidic chips have been fabricated in Pyrex glass to study electrokinetic pumping generated by a low-voltage ac bias applied to an in-channel asymmetric metallic electrode array. A measurement procedure has been established and followed carefully resulting in a high degree of reproducibility of the measurements over several days. A large coverage fraction of the electrode array in the microfluidic channels has led to an increased sensitivity allowing for pumping measurements at low bias voltages. Depending on the ionic concentration a hitherto unobserved reversal of the pumping direction has been measured in a regime, where both the applied voltage and the frequency are low, V(rms)<1.5 V and f<20 kHz , compared to previously investigated parameter ranges. The impedance spectrum has been thoroughly measured and analyzed in terms of an equivalent circuit diagram to rule out trivial circuit explanations of our findings. Our observations agree qualitatively, but not quantitatively, with theoretical electrokinetic models published in the literature.

AC electroosmotic pump with bubble-free palladium electrodes and rectifying polymer membrane valves.

We present the design, test and theoretical analysis of a novel micropump. The purpose is to make a pump with large flow rate (approximately 10 microL min-1) and high pressure capacity (approximately 1 bar) powered by a low voltage DeltaV<30 V. The pump is operated in AC mode with an electroosmotic actuator in connection with a full wave rectifying valve system. Individual valves are based on a flexible membrane with a slit. Bubble-free palladium electrodes are implemented in order to increase the range of applications and reduce maintenance.

Long-term stable electroosmotic pump with ion exchange membranes.

We present the design, fabrication and test of a novel inline frit-based electroosmotic (EO) pump with ion exchange membranes. The pump is more stable than previous types due to a new flow component that ensures a controlled width of the diffusion layer close to the ion exchange membranes. The pump casing is constructed in polymers while the EO active part, the frit, is made in a nanoporous silica. The pressure capability of the pump is Deltapm/DeltaV = 0.15 bar V(-1). The flow rate to current ratio is Qm/I = 6 microL min(-1) mA(-1). This translates to Deltapm = 4.5 bar and Qm = 6 microL min(-1) at DeltaV = 30 V. The pump has been tested with four different buffer concentrations. In order to investigate day-to-day reproducibility each Q-p pump characteristic has been recorded several times during hour-long operation runs under realistic operating conditions.