Enhancing pharmaceutical crystallization in a flow crystallizer with ultrasound: Anti-solvent crystallization.

Continuous crystallization is a fast growing application domain in the pharmaceutical industry. Application of ultrasound has been proven to have positive effects like reduction in induction time and Metastable Zone Width (MSZW) in both batch and flow systems. Further understanding of flow-based sonocrystallization is required to achieve industrial level scale up. This work investigates the sonocrystallization of pharmaceutical compounds in a tubular flow crystallizer. Acetyl Salicylic Acid (ASA-Aspirin) is used as a model compound with ethanol and water as solvent and anti-solvent, respectively. Experiments were conducted in silent and sonicated conditions to study the MSZW. Ultrasound made it possible to achieve crystallization within the crystallizer which was not possible in silent conditions, under the tested conditions. Continuous crystallization was achieved at as low as 48 wt% of anti-solvent and crystallization was already seen at a supersaturation of 1.02. In some experiments, temperature rise with ultrasound caused the crystals to re-dissolve within the channels. Better crystallization - no re-dissolution - was achieved by using low ultrasonic power without any loss in the yield. Particle sizes of product crystals were in the range of 4-46 µm. In conclusion, ultrasound was highly effective in enabling anti-solvent crystallization of a pharmaceutical compound in a tubular flow crystallizer.

Technical and clinical validation of three commercial real-time PCR kits for the diagnosis of neuroborreliosis in cerebrospinal fluid on three different real-time PCR platforms.

This study reports the evaluation of the technical and clinical validation of the O-DiaBorburg kit (DIA), Borrelia burgdorferi PCR kit, ISEX (GENE), and Borrelia burgdorferi sensu lato Real-TM (SAC) for the diagnosis of neuroborreliosis in cerebrospinal fluid based on both Borrelia DNA and CSF samples from patients with clinical suspicion of neuroborreliosis. This validation study was done by analysing the kits on the Rotorgene Q (RGQ), CFX96, and LightCycler480 (LC480). For all kits, the linear range was larger on RGQ than on CFX96 and LC480. A good reproducibility was obtained for all assays on all instruments. Storage at -20 °C resulted in a decreased reproducibility for SAC. Results of the limit of detection (LOD95) experiments indicated a better sensitivity than described in the kit insert for all kits on all PCR platforms. No cross-reactivity was found for genetically related organisms nor for other pathogens which may be present in CSF. All species of the Borrelia burgdorferi sensu lato complex were detected with the GENE and SAC kits. The DIA kit failed to detect B. lusitaniae. The results seemed to indicate a better overall performance for the GENE kit on RGQ. However, its diagnostic value could not be confirmed in the clinical validation study, wherein none of the 103 CSF samples from clinical neuroborreliosis cases showed a positive real-time PCR result with the GENE kit analysed on RGQ.

Influence of dissolved gases on sonochemistry and sonoluminescence in a flow reactor.

In the present work, the influence of gas addition is investigated on both sonoluminescence (SL) and radical formation at 47 and 248 kHz. The frequencies chosen in this study generate two distinct bubble types, allowing to generalize the conclusions for other ultrasonic reactors. In this case, 47 kHz provides transient bubbles, while stable ones dominate at 248 kHz. For both bubble types, the hydroxyl radical and SL yield under gas addition followed the sequence: Ar>Air>N2>>CO2. A comprehensive interpretation is given for these results, based on a combination of thermal gas properties, chemical reactions occurring within the cavitation bubble, and the amount of bubbles. Furthermore, in the cases where argon, air and nitrogen were bubbled, a reasonable correlation existed between the OH-radical yield and the SL signal, being most pronounced under stable cavitation at 248 kHz. Presuming that SL and OH originate from different bubble populations, the results indicate that both populations respond similarly to a change in acoustic power and dissolved gas. Consequently, in the presence of non-volatile pollutants that do not quench SL, sonoluminescence can be used as an online tool to qualitatively monitor radical formation.

Characterization of stable and transient cavitation bubbles in a milliflow reactor using a multibubble sonoluminescence quenching technique.

The bubble type, generated by an ultrasonic field, was studied in a batch and flow reactor using a multibubble sonoluminescence (MBSL) quenching technique with propanol and acetone. The influence of frequency and transducer configuration was evaluated using the same piezoelectric element in both setups. Results show that the bubble type not only depends on the frequency, but also on the input power or transducer configuration. Additionally, the effect of flow on sonoluminescence yield and bubble type was studied in the continuous setup at various frequencies. As the flow becomes turbulent, the sonoluminescence signal reaches a plateau for three out of four frequencies, and a transition from transient to stable cavitation occurs for frequencies below 200 kHz.

Potential of activated carbon to recover randomly-methylated-ß-cyclodextrin solution from washing water originating from in situ soil flushing.

Despite the overall high efficacy of cyclodextrins to accelerate the treatment of soil aquifer remediation by in-situ soil flushing, the use in practice remains limited because of the high costs of cyclodextrin and high concentrations needed to significantly reduce the treatment time. The current study tested the potential of activated carbon to treat washing water originating from soil flushing in order to selectively separate hydrocarbon contaminants from washing water containing cyclodextrin and subsequently reuse the cyclodextrin solution for reinfiltration. A high recovery of the cyclodextrin from the washing water would reduce the costs and would make the technique economically feasible for soil remediation. This study aimed to investigate whether cyclodextrin can pass through the activated carbon filter without reducing the cyclodextrin concentration when the contaminated washing water is treated and whether the presence of cyclodextrin negatively affects the purification potential of activated carbon to remove the organic pollutants from the pumped soil water. Lab-scale column experiments showed that with the appropriate activated carbon 100% of cyclodextrin (randomly-methylated-ß-cyclodextrin) can be recovered from the washing water and that the effect on the efficiency of activated carbon to remove the hydrocarbon contaminants remains limited. These results show that additional field tests are useful to make in-situ soil flushing with cyclodextrin both a technical and an economical interesting technique. These results might stimulate the application of cyclodextrin in soil treatment technology.

AOX removal from industrial wastewaters using advanced oxidation processes: assessment of a combined chemical-biological oxidation.

In this paper, the abatement of adsorbable halogenated organic compounds (AOX) from an industrial wastewater containing relatively high chloride concentrations by a combined chemical and biological oxidation is assessed. For chemical oxidation, the O(3)/UV, H(2)O(2)/UV and photo-Fenton processes are evaluated on pilot scale. Biological oxidation is simulated in a 4 h respirometry experiment with periodic aeration. The results show that a selective degradation of AOX with respect to the matrix compounds (expressed as chemical oxygen demand) could be achieved. For O(3)/UV, lowering the ratio of O(3) dosage to UV intensity leads to a better selectivity for AOX. During O(3)-based experiments, the AOX removal is generally less than during the H(2)O(2)-based experiments. However, after biological oxidation, the AOX levels are comparable. For H(2)O(2)/UV, optimal operating parameters for UV and H(2)O(2) dosage are next determined in a second run with another wastewater sample.

Regeneration of brewery waste water using nanofiltration.

The brewing industry is a large consumer of groundwater for brewing, rinsing and cooling purposes. As regulations become more and more stringent and the cost of water increases, water recycling gains interest. This paper investigates the possibilities of nanofiltration for the treatment of brewery waste water streams in view of recycling. Four different water streams (waste water after biological treatment, bottle rinsing water, rinsing water of the brewing room and rinsing water of the bright beer reservoir) were filtered with four different nanofiltration membranes (UTC-20, UTC-60, Desal-HL-51 and Desal-5-DK). The results for the biologically treated waste water were the most promising. For the other streams, rejection of organics was insufficient to obtain the required quality, mainly due to the high concentrations of organics such as ethanol in the feed water. Over the periods considered (3 h) only moderate flux decline (10-40%) was observed for most membranes and feed solutions. For Desal-5-DK at high pH, an increase of the flux was observed.