Process parameter dependent growth phenomena of naproxen nanosuspension manufactured by wet media milling.

The production of nanosuspensions has proved to be an effective method for overcoming bioavailability challenges of poorly water soluble drugs. Wet milling in stirred media mills and planetary ball mills has become an established top-down-method for producing such drug nanosuspensions. The quality of the resulting nanosuspension is determined by the stability against agglomeration on the one hand, and the process parameters of the mill on the other hand. In order to understand the occurring dependencies, a detailed screening study, not only on adequate stabilizers, but also on their optimum concentration was carried out for the active pharmaceutical ingredient (API) naproxen in a planetary ball mill. The type and concentration of the stabilizer had a pronounced influence on the minimum particle size obtained. With the best formulation the influence of the relevant process parameters on product quality was investigated to determine the grinding limit of naproxen. Besides the well known phenomenon of particle agglomeration, actual naproxen crystal growth and morphology alterations occurred during the process which has not been observed before. It was shown that, by adjusting the process parameters, those effects could be reduced or eliminated. Thus, besides real grinding and agglomeration a process parameter dependent ripening of the naproxen particles was identified to be a concurrent effect during the naproxen fine grinding process.

Impact of colloidal and soluble organic material on membrane performance in membrane bioreactors for municipal wastewater treatment.

Two parallel membrane bioreactors (2 m3 each) were operated over a period of 2 years. Both pilots were optimised for nitrification, denitrification, and enhanced biological phosphorous elimination, treating identical municipal wastewater under comparable operating conditions. The only constructional difference between the pilots was the position of the denitrification zone (pre-denitrification in pilot 1 and post-denitrification in pilot 2). Despite identical modules and conditions, the two MBRs showed different permeabilities and fouling rates. The differences were not related to the denitrification scheme. In order to find an explanation for the different membrane performances, a one-year investigation was initiated and the membrane performance as well as the operating regime and characteristics of the activated sludge were closely studied. MLSS concentrations, solid retention time, loading rates, and filtration flux were found not to be responsible for the different performance of the submerged modules. These parameters were kept identical in the two pilot plants. Instead, the non-settable fraction of the sludges (soluble and colloidal material, i.e. polysaccharides, proteins and organic colloids) was found to impact fouling and to cause the difference in membrane performance between the two MBR. This fraction was analysed by spectrophotometric and size exclusion chromatography (SEC) methods. In a second step, the origin of these substances was investigated. The results point to microbiologically produced substances such as extracellular polymeric substances (EPS) or soluble microbial products (SMP).

Correlation between membrane fouling and soluble/colloidal organic substances in membrane bioreactors for municipal wastewater treatment.

Two similar membrane bioreactors of 2 m3 each were operated in parallel over two years under the same operational conditions, fed with the same municipal wastewater. The only process and operational difference between both pilot plants was the position of the denitrification zone (pre-denitrification in pilot 1 and post-denitrification in pilot 2). Despite parallel operation, the two MBRs exhibited different fouling rates and decreases in permeability. These differences could not be accounted for by MLSS concentrations, loading rates, or filtration flux. In a one-year investigation, soluble and colloidal organic material in the activated sludge of both MBR was regularly analysed by spectrophotometric and Size Exclusion Chromatography (SEC) methods. The larger organic molecules present in the sludge water phase (i.e. polysaccharides, proteins and organic colloids) originating from microbial activity (extracellular polymeric substances) were found to impact on the fouling and to explain the difference in membrane performance between the two MBR units. In both pilot plants, a linear relationship could be clearly demonstrated between the fouling rate of the membrane and the concentration of polysaccharides in the sludge water phase during a 5 month operational period at an SRT of 8 days.

Organic colloids and their influence on low-pressure membrane filtration.

Wastewater treatment by low-pressure membrane filtration (MF and UF) is affected to a large extent by macromolecules and colloids. In order to investigate the influence of organic colloids on the membrane filtration process, colloids were isolated from a wastewater treatment plant effluent using a rotary-evaporation pre-concentration step followed by dialysis. Stirred cell tests were carried out using redissolved colloids, with and without additional glass fiber filtration. After constant pressure membrane filtration of 190 L/m2, the initial flux had declined by 50% for colloids > 6-8 kD (glass fiber filtered) with a hydrophilic MF membrane and for colloids > 12-14 kD (glass fiber filtered) with a hydrophobic MF membrane. For the non-filtered colloidal solutions, the flux decline was even steeper with the flux being below 10% of the initial flux after 190 L/m2 were passed through the membranes. As with larger particles, colloids form a filtration cake layer on top of the membrane surface when used as isolates without prior filtration. This filtration cake is easily removed during backwashing. However, polysaccharides as a macromolecular component of the colloid isolate cause severe fouling by the formation of a gel layer on the membrane surface that is difficult to remove completely.