Second order nonlinear optical imaging of solid state crystallization

Duangporn Wanapun, Purdue University

Abstract

Second order nonlinear optical imaging of chiral crystals (SONICC) was applied to study crystallization of amorphous solid emphasizing the application in pharmaceutical research. Second harmonic generation, a fundamental phenomenon underpinning the technique is selective to systems without inversion symmetry including crystals of chiral molecules such as a majority of active pharmaceutical ingredient. SONICC was applied to monitor crystal formation of active pharmaceutical ingredients (APIs) and it demonstrated 8 order of magnitude improvement of detection limit compared to conventional macroscopic methods. Kinetics of crystallization of an API was investigated and the results showed that the energy barrier of crystallization analyzed using SONICC is in good agreement with the energy barrier estimated by traditional thermal analysis. Furthermore, SONICC was used to explore the effect of mechanical milling on a reduction of API crystallinity. SONICC enables lower detection limit than powder X-ray diffraction. In addition to improvement in detection limit, SONICC enables selective detection of crystals within bulk scattering powder and allows accessing microscopic information including crystal nucleation and crystal size distribution. These studies collectively suggest that SONICC can potentially be an alternative technique for characterizing crystals of APIs.

Degree

Ph.D.

Advisors

Simpson, Purdue University.

Subject Area

Physical chemistry

COinS