1. EPSRC Portfolio Partnership in Complex Fluids and Complex Flows Nanofiltration of Pharmaceuticals: Theory and Practice Nanofiltration MF SUSPENDED PARTICLES UF MACROMOLECULES NF SUGARS DIVALENT SALTS DISSOCIATED ACIDS RO MONOVALENT SALTS UNDISSOCIATED ACIDS WATER Used for the fractionation and purification of small organics and salts (~ MW < 1000) Pore radii in the range of less than 2 nm. Pore size distributions. Steric or size based exclusion. Donnan or charged based exclusion Dielectric exclusion ------ Negatively charged membrane Direction of flux - - + Feed + Membrane Theory Flux through NF membranes is described by the extended Nernst-Planck equation: ConvectionDiffusionElectrical Pressure Describes the transport of a solute through the membrane internal structure. The first two terms are relatively small and the first term is neglected in subsequent calculations. rearranged to give: Where Linear Transport Where Equilibrium Partitioning Steric Donnan Dielectric Where Bulk Feed Membrane Bulk Permeate Equilibrium Transport The models have three main parameters: Effective membrane pore radius Pore solvent dielectric constant Effective membrane charge density (6R,7R)-3-carbamoyloxymethyl-7-[(Z)-2-(fur-2-yl)-2- methoxyimino-acetamido] ceph-3-em-4-carboxylic acid 2 nd gen Cephalosporin Cefuroxime sodium Antibiotic Process Description Final stage Crystallization Process fluid Excess sodium lactate Cefuroxime product Waste stream The efficiency of the crystallisation is not 100%. Is it possible to recycle the cefuroxime ? Typically produced on a 100 Te/year plant 1 Typical value of $100 per kg 1 % increase in yield gives $100k/year Typical yields for crystallisation 30 – 60 % 2,3 We will assume 70 % 1. Ghosh et al., Adv. Biochem. Eng. Biotech., 56 (1997). 2. Al-Zoubi and Malamataris, Int. J. Pharmaceutics, 260 (2003) 123. 3. De Faveri et al., J. Food Eng., In press. Membrane properties Depends also on solution properties 6.3 m 3 140 mol m -3 Cefuroxime 2,230 mol m -3 lactate 98 mol m -3 Cef. (Now solid product) 42 mol m -3 Cef. 2,230 mol m -3 Lac. Nanomax™-50 Desal-5-DK SelRO® MPF-44 3 commercially available membranes were used 0.55 nm 0.52 nm 0.49 nm Pore radii Component Rejection Cefuroxime Sodium lactate Nanomax™-50 membraneDesal-5-DK membrane Cefuroxime Sodium lactate SelRO® MPF-44 membrane Sodium lactate Glucose Nanomax™-50Desal-5-DK R(Cef) > 89 % R(Lac) = good R(Cef) > 99.7 % R(Lac) = reasonable NoYes Rejection of Mixtures R(Cef) > 99.5 % R(Lac) = reasonable Charge Profile Diafiltration R(Cef) > 99.7 % 99.6 % recovery Lactate reduced by a factor of 2.5 Penicillin alternative Gram (+) cocci Assumptions made: Spiral wound membranes Cross flow is sufficient to avoid mass transfer effects Osmotic pressure described by Van’t Hoff equation 1 in 5 dilution of waste stream made 3 MPa operating pressure Industrial Recovery Feeding all the data into the model gives: Recovery of sodium cefuroxime is 98.5 %. Production of sodium cefuroxime is reduced from 877 moles/day to 618 moles/day. This is a saving of 116 kg/day. The overall recovery efficiency will increase from 70 % to 99.3 %. No extra burden is placed on the crystallization unit as the throughput is the same. Conclusions This work demonstrates that NF modelling is viable for real industrial separations. We need further industrial collaborations to increase model use and effectiveness. Ideally with cheap materials so pilot scale can be used without major financial investment. Development of a computer simulation package for non-specialised engineers. Outlook PRIFYSGOL CYMRU ABERTAWE UNIVERSITY OF WALES SWANSEA