Real-time concentration determination is critical in process analytical technology for advance quality control of crystallization. A novel approach is presented to correlate in-situ concentration of paracetamol in ethanol solution with the attenuated total reflection/ultraviolet (ATR-UV) spectrum by using the partial least squares method. The correlated concentrations are well consistent with the measurement of gravimetric method and the root-mean-square derivation is found to be 0.0075. Supersaturation correlation based on the developed ATR-UV in-situ concentration measurement

coupled with focused beam reflection measurement for monitoring the nucleation and growth during crystallization procedure

is utilized to investigate the effect of three cooling policies on cooling crystallization

i.e.

natural cooling policy (NCP)

linear cooling policy (LCP) and control cooling policy (CCP). The results show that the CCP has advantages over NCP and LCP in producing more crystals with the large and well-distributed crystal sizes.