Application of OSN in membrane cascade for purification of the API Amoxicillin

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

The present work developed at Imperial College London (ICL) in collaboration with the Massachusetts Institute of Technology (MIT) had the objective of purifying the API amoxicillin containing an initial concentration of 30ppm of the compound 4-hydroxy-l-phenylglycine (impurity) using an OSN membrane cascade. Project proposal:  Solubility and stability studies of the API in different solvents.  Solvent choice for the separation process.  Dissociation study of the API and impurity to exploit a promising optimization of the process.  Membrane screening using dead-end and m-CSTR upside-down measurements.  Process modeling and simulation of different configurations Amoxicillin showed to be a sensitive compound to work with having a low solubility and a fast decomposition in the studied solvents. The solvents tested in detail were water, acetone, ethanol and methanol, being water the one choose to performed the purification. From the dissociation study it was possible to understand the possible exploitation of the pH parameter in the optimization of the separation process. In the membrane screening the effect of pressure and pH were studied in six types of membranes. It could be conclude that the main obstacle for the purification process was the membrane performance itself, with insufficient separation between the compounds (difference of 10 p.p. in rejection). The most promising results were obtained using the TFNF-DL membrane, with an API rejection of 99.12% and an impurity rejection of 87.80%. The process modelling was performed in a semi-batch mode with one and two stages, respectively, and in continuous mode with two-stages and two different configurations. An increase from two to three stages was also analyzed for the continuous configuration II. A maximum purity of 99.65% with a yield of 97.86% was obtained with the semi-batch two-stage cascade system. From the continuous three stage cascade system, a purity of 98.65% and a yield of 98.54% were achieved.