The pharmaceutical industry must address the release of nonbiodegradable APIs into the environment, and the objective of this study was to develop a solution for treating an aqueous process waste stream that contained APIs and an organic solvent. It was found that solvent-stable nanofiltration (NF) membranes displayed the potential to produce a filtered stream suitable for discharge to the conventional chemical treatment plant, as well as enabling a 70% waste stream volume reduction. The developed process resulted in the installation of a system that would enable future production expansion to take place without an increase in energy requirements.

The route for waste

On the go...

Pharma's use of thermal oxidation is a well-established disposal route for waste streams containing organic solvents and APIs that cannot be inactivated by conventional chemical and biological waste water treatment techniques. Thermal oxidation is very effective for such waste streams, but it uses an uneconomical amount of energy for high water, low organic solvent and contaminant content streams. Because of high capital and operating costs, as well as environmental constraints, this study investigates and develops a solution based on membrane technology, which offers an energy efficient and 'green' technology process.

A client's site that manufactures APIs by a multiple step chemical synthesis process, which results in waste streams of varying composition, was examined. The aqueous waste stream contains <2% organic solvent, mono and divalent salts, APIs and byproducts. The study objective was to reduce the waste stream volume by ~70% and permeate quality compliant with site discharge limits for the APIs.

Waste stream characterization dictated a requirement for a membrane that would be stable with the site process organic solvent and provide a high rejection of the ~650 MW API. Reverse osmosis (RO) membranes offer a significantly high rejection of the target molecule, but, unfortunately, current state-of-the-art technology for these membranes does not provide long-term membrane integrity in the presence of the organic solvent.

The characteristics of the SelRO¹NF MPS-44 hydrophilic membrane (Koch Membrane Systems; MA, USA) offered the potential for retention of the API and stability with the organic solvent.

NF separations with complex streams are difficult to predict or model without experimental data. A series of membrane filtration tests was required to establish proof of concept, and the results provided confidence to embark on pilot site trials to obtain the data required for production scale-up of the custom-designed waste treatment system. In this work, the approach to trials and some of the results are presented.

Figure 1: Crossflow flat sheet test cell.

Methods and material Process stream characterization.The process waste stream from the API synthesis reactor sequences was collected in the aqueous waste tank (Figure 1). Initial proof-of-concept test work conducted trials on grab samples to establish API rejection. Pilot trials were conducted with composite samples for process development trials.

Figure 2: Pilot trials plant.

Proof-of-concept trials.A flat sheet test cell was used to verify the initial rejection profile of the key components with the SelRO MPF-44 NF membrane at 10–35 bar operating pressure (Figure 2). The membrane sample was soaked in concentrated feed material for 12 months to establish membrane integrity.