Prediction of partitioning coefficients: potential for drug formulations and bioseparation technologies
Advancing the chemical engineering fundamentals
Interfacial & Colloidal Phenomena - II (T2-6b)
Keywords: Partitioning coefficients, micelles, COSMO-RS, UNIFAC
Solubilization of solutes in micellar solutions is a process having a wide range of application, Some examples are: detergency, enhancing the aqueous solubility of hydrophobic drugs or separation of products of biosynthesis. The measure of solubilization is a solute partitioning coefficient between the micellar and aqueous phase (Kmw). In pharmaceutical industry, the knowledge of the partitioning of drug candidates in the different media of the human body (n-octanol/water, Kow, or the micelle/water partition coefficient) is of importance at the early stage of the design process and should be known from measurements or calculations. In case of biosynthesis, the separation of products from the reaction media is often made by adding surfactants to the system followed by the separation of the product-containing micellar phase by filtration. In this case, the proper information on Kmw is essential for choosing the surfactant with the highest selectivity. In such applications, the possibility to predict the partitioning of the substance under investigation in solutions containing different surfactants would be especially valuable. Presently, only few models exist allowing the prediction of Kmw. All of them belong to the class of linear correlations between some molecular properties and log(Kmw) values.
The aim of this work is to show that the thermodynamically based models can be effectively utilised to predict the drug partitioning, and the prediction can be achieved quantitatively based solely on the chemical structure of the substances. Furthermore, such models account for the concentration of each ingredient and temperature, so they can be utilised to predict how the solute partitioning changes when these conditions are varied. Two models are examined here: the structure-interpolating UNIFAC model and the a-priori COSMO-RS model. The partitioning of a variety of solute classes in aqueous solutions of nonionic and ionic surfactants is investigated. The theoretically predicted partition coefficients were found to be in good quantitative agreement with the experimentally measured ones. The theoretical approaches can be extended and applied to multicomponent systems (mixtures of solutes and/or mixtures of surfactants). Effects of temperature and concentration can be examined. The results of the modeling can be used for the prediction of the enhanced drug solubilisation as well as for the optimization of separation and purification processes in biotechnology and pharmaceutical industry.
Presented Thursday 20, 09:25 to 09:45, in session Interfacial & Colloidal Phenomena - II (T2-6b).
