Nonlinear optical imaging of pharmaceutical formulations.

摘要

Nonlinear optical (NLO) techniques such as second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon excited ultraviolet fluorescence (TPE-UVF) were applied toward various pharmaceutical and biological applications, allowing for the selective and sensitive detection of protein crystals and quantitation of low levels of active pharmaceutical ingredient (API) crystallinity within a wide variety of formulations and conditions. Commonly utilized pharmaceutical formulations and a wide variety of excipients were assessed for their potential NLO background contributions with SHG, TPEF, and TPE-UVF. Also examined was the wide range of SHG and TPEF responses arising from different APIs. A library of nearly 40 APIs was examined, and the resultant NLO intensities spanned seven orders of magnitude. The high temporal and spatial resolution of NLO microscopy can also allow for the performing of measurements quantifying nucleation, crystallization, and dissolution rates, over time with varying temperature and humidity conditions. Furthermore, a combined NLO and synchrotron X-ray diffraction (XRD) system was implemented to decrease the detection limits of XRD, while simultaneously allowing for the elucidation of structural information.