A critical review and analysis of thermodynamic and kinetic effects on extraction of medical devices by organic solvents as a sample preparation step in devices’ chemical characterization

ABSTRACT The extraction of medical devices by organic solvents as a sample preparation step is perhaps the most critical process in chemical characterization of medical devices, as the decision of solvent choice determines not only the resulting extractables profiles ( e.g. , the number, molecular weight, and concentration of extractables), but also the degree of analytical challenges in identification and quantification, when performing instrumental analysis of extracts. Both concentration and chemical identities of all extractables are used in subsequent toxicological risk assessment, which is required to support regulatory submission and approval of medical devices. There is currently a considerable debate on which solvent(s) should be used to balance the desired extraction and clinical relevance to biological tissue exposure due to scientific and regulatory consequences. The purpose of this article is intended to streamline solvent selection in chemical characterization, particularly on the rational development of a semipolar solvent to stimulate or exaggerate biological (storage) fatty tissues. A comprehensive review and analysis of solvent extraction of polymer materials from thermodynamic and kinetic perspectives is provided first. The solvent-material interactions (swelling) and their consequences on kinetics and thermodynamics are subsequently elaborated. The conclusions of thermodynamic and kinetic properties, together with solvent-material interactions, are used to establish solvent similarity criteria between semipolar solvents and fatty tissues. Finally, solvent solubility, degree of material swelling by solvents, diffusion coefficients in device material, partition coefficient between material and solvent, and solvent compatibility with instrumental analysis are used as the criteria to establish representative solvents to fatty tissues in chemical characterization studies. Blood simulating solvents are well established and not discussed in the article.