Determination of the optical second harmonic response of pharmaceutical solid–solid mixtures

We report on a new method for characterising crystallinity and polymorphism of pharmaceutical drugs and excipients in the solid state. The optical nonlinearity of certain crystalline structures allows under certain circumstances the quantitative determination of polymorphism or crystallinity. An apparatus was set up to measure the second harmonic response of powdered samples when irradiated with a pulsed laser source. Here we present experimental results from various pharmaceutically interesting materials. This rapid, novel technique has potential for industrial monitoring of pharmaceutical manufacturing processes.