The purpose of this study was to monitor a crystallization process by near-infrared (NIPR) spectroscopy involving α-form and γ-form of indomethacin (IMC).IMC has a complicated polymorphism consisting of five true polymorphs.Two most frequently used polymorphs are stable γ-form and recta-stable α-form [1].The biological absorption rate of α-form was reported to be substantially greater than that of y-form.Also,the rectal absorption rate of α-form in rats was better as well [2].Principal component analysis (PCA) was applied to interpret NIR in-line spectra.Characteristics of intermediate crystals sampled in process of crystallization were measured using X-ray powder diffraction (XRD) and optical microscopy (OMD,followed by a correlation with PCA results.Polymorphic transformation from y-form to α-form was achieved by two methods:pouring solution into an anti-solvent,and pouring an anti-solvent into the solution.The former method resulted in IMC powder of mixed polymorphs (7-form and α-form),whereas the latter method produced α-form only powder.These two polymorphs are formed in distinctively different shape:plate-like γ-form and needle-like α-form.It was demonstrated that the IMC crystallization process takes place in multiple steps and each process can be monitored with PCA score plots.In addition,each step was well matched with XRD and OM measurements.Conclusively,the NIR in-line monitoring can be effectively applied to observe and predict key quality attributes of crystals such as polymorph or size during a pharmaceutical crystallization process.