Optimization of Reaction Conditions in the Production of Gadolinium Diethylenetriamine Pentaacetate-Folate

Abstract

A previous study has performed the laboratory-scale synthesis and characterization of Gadolinium Diethylenetriaminepentaacetate-Folate. Some parameters associated with the synthesis have been defined. In current study was focused on establishment the parameters for scaling up the production of Gadolinium Diethylenetriaminepentaacetate-Folate as a targeted MRI contrast agent. For the purpose of subsequent scaling up the synthesis, the parameters particularly those determining the yield of the reaction product should be established. This report presents the use of The Placket Burman Design and the Response Surface Methodology in establishing the parameters. Thus, following the Placket Burman Design, a number of synthesis reactions were carried out, each with different reaction conditions, with respect to parameters to include: mole ratio of reactants (i.e mole of Gd3+ to DTPA-Folate), time of reaction, temperature, stirring rate, pH and solvent volume. Using this method, a conclusion could be drawn that the three factors were found to be significant. To get final conclusions on the optimal synthesis reaction conditions, the Response Surface Methodology was then applied. For this purpose, again, some synthesis reactions experiments were performed. These were done, in accordance to the Response Surface Methodology, verified by analysis of countour plots, helped to locate the optimal value of the factors. The resulted data showed that for optimal yield of the synthesis reaction there were three dominant parameters. They were mole ratio of reactants, stirring rate process, and the volume of water.