Clavulanic acid concentration and purification by nanofiltration

Author(s)

Andrea Limoeiro Carvalho

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia de Alimentos
• Defense date: 2011-05-04

Examining board members

Francisco Maugeri Filho; Clóvis Sacardo da Silva; Luiz Antonio Viotto; Marco Di Luccio; Raquel Cristine Kuhn

• Advisor: Francisco Maugeri Filho

Abstract

Nanofiltration is a pressure driven membrane process, with desorption and diffusion, which is also applied to the concentration of clavulanic acid from a clarified juice. In this study, clavulanic acid was concentrated, and the process had its efficiency evaluated and its mass transfer parameters studied and applied to the mathematical model SEDE-VCh, and in addition scale up was also evaluated. This study was divided into the following stages: selection and characterization of the membranes, and the application of the model, in which experiments were performed to evaluate the performance of the NF and NF90 membranes (both FilmtecTM), and NP010 and NP030 (both Microdyne Nadir®), and the scale up of the process, in which the membrane that showed the best results in the previous steps was used. Concerning the selection of the membrane, the evaluated responses were the retention coefficient, productivity and purification factor. In the characterization of the membrane step, we evaluated the surface morphology of the four membranes, targeting the pore size and pore size distribution, roughness, fractal dimension and permeability, in addition to studies that provided data on the electrical and steric effects over the transport through the membranes, as their surface and volumetric density charges, the concentration of solute in its external surfaces and the mass transfer coefficient of the process. From these data a model was created to explain the transport through the membranes. Finally experiments were carried out to verify the behavior of the process in a pilot scale. The results showed that the NF membrane is best for the process of concentration of clavulanic acid with retention coefficient average of 0.988 in bench scale and almost 1.0 in the pilot plant. All the four membranes had pore radii below 1 nm and an isoelectric point between pH 5 and 6. The NP010 membrane showed the higher water permeability, in the following order: NP010 > NP030 > NF > NF90. This parameter is related linearly with the average pore size and its reduction increases with the difference between the fractal dimension before and after the use of the membranes. It was also verified that at high adsorption the roughness of the membranes tends to be similar. The NF90 membrane showed a higher mass transfer coefficient, followed by NF, NP010 and NP030, in that order and the rejection varied with the pH for the NF and NF90 membranes. The dielectric constant inside the pores increases inversely with pore size of the membranes even when it reaches the value of free water. The selectivity of the membrane to KCl and clavulanic acid shows the same trend as the volumetric density charge: NF > NF90 > NP030 _ NP010. By means of the studies of scale up it was determined that the conventional system with a stirrer that promotes the convection movement in the process can be used in other studies of process evaluation and selection of membranes in view of industrial application, and also that peptide and mino acid substances improve the process concentration of clavulanic acid by nanofiltration. The final productivity was about 6.4 [CA]RET/[CA]0.L.h. (AU)