A previous post discussed the degree of crystallinity of ethylene vinyl acetate (EVA) copolymers and its dependence on the vinyl acetate (VA) content of the polymer. Differing degrees of crystallinity in turn result in different melting temperature ranges as a function of VA content. The melting point temperature is reduced with increasing VA content due to the resulting reduction of the thickness of the crystalline lamella, which are comprised only of series of ethylene units not interrupted by incorporation of a VA unit. As more VA is randomly incorporated into the polymer backbone, the average block length of sequential ethylene units becomes shorter, resulting in fewer, thinner crystals which have lower melting temperatures. The melting range is then comprised of a distribution of melting points reflecting the distribution of crystal thicknesses which arise from the statistical distribution of ethylene block lengths around the average. If one measures the melting process using differential scanning calorimetry (DSC), an analytical technique that measures the heat flow required to change the temperature of a specimen, the melting event will appear as a broad peak across a temperature range with the maximum rate of heat flow into the sample typically designated the “peak melting temperature”. Of course, the exact position and shape of that peak depends on heating rate and heat history of the sample, but the “peak melting temperature” will correlate rather well with the VA content in EVA copolymers, as illustrated here for typical EVA copolymers.
There are additional effects which influence crystallization dynamics and thus the melting point distribution. These include average molecular weight, molecular weight distribution, and polymerization process conditions, the latter of which can influence the degree of short and long chain branching. I’ll discuss how branches form and their influence on polymer properties in my next post.
So what is the significance of this relatively low and controllable melting temperature range for pharmaceutical excipient applications? It means that active ingredients and other excipients can be melt compounded with EVA at relatively low temperatures, thus potentially avoiding thermal degradation of, or thermally induced reactions among, those components. EVA can be compounded and/or fabricated at as little as 20 to 40°C above its peak melting point, depending on the process chosen and other criteria. EVA alone is relatively stable to thermal degradation, but will begin to slowly degrade at measurable rate, typically with evolution of acetic acid, above around 200 to 220°C. However, the available temperature range between the required threshold processing temperature and the temperature of onset of any degradation or undesired reaction can often be quite sufficient to allow a robust formulation process with the targeted ingredients. Therefore, EVA is a potential candidate to consider in the formulation of pharmaceuticals via melt extrusion.