Estimation of Kinetics for Batch Cooling Crystallization by Focused‐Beam Reflectance Measurements

Abstract

Numerical simulation of the seeded batch cooling crystallization process of active pharmaceutical ingredients was performed. Crystal size distribution was observed by focused-beam reflectance measurements and concentration by simultaneous Fourier transform infrared spectroscopy. First, kinetic parameters were estimated. Nucleation rate coefficient and order were estimated from the linear regression equation between cooling rate and metastable zone width. The remaining parameters were estimated from the evaluation function. Then, the numerical simulation was performed by utilizing the method of moments. Finally, observed data were compared with simulated data. The simulated values of mean mass size corresponded reasonably with the observed ones.An ethanolic solution of acetaminophen (CH 3 CONHC 6 H 4 OH, AAP) and an aqueous solution of L-arginine (C 6 H 14 N 4 O 2 , Arg) were selected as target substances. Physical properties of these substances are listed in Tab. 1.

Partial Seeding Policy for Controlling the Crystal Quality in Batch Cooling Crystallization

“…Here, R is the gas constant, T is the absolute temperature, Δ T is the super‐cooling, σ is the relative supersaturation, k b0 , E b , and b are the nucleation rate constant, the activation energy, and the order, respectively, and k g0 , E g , and g are the growth rate constant, the activation energy, and the order, respectively. The kinetic parameters in the above equations were estimated in the previous study and are listed in Tab. .…”

Computing Crystal Size Distribution by Focused‐Beam Reflectance Measurement when Aspect Ratio Varies

“…Each element of the shape transformation matrix S corresponds with the ratio of the probability event of each chord length range in the sample space of the domains of five independent variables and can be computed with Monte Carlo analysis . For example, ( S ) ij corresponds with the probability that the chord length defined by five independent variables, the values of which are uniformly random within the domain of the j ‐th bin in CSD, is present within the range of the i‐ th bin in CLD.…”

“…In previous work , the algorithm of the computation of the mapping matrix which can afford to take into account the change in crystal shape was described. In this study, the suspension of L ‐arginine (Arg) in water was used.…”

Impact of Ultrasound Amplitude on Crystallization of Borax Decahydrate in a Stirred‐Batch Crystallizer

“…In any case, previous studies have shown that sonication during crystallization can affect the induction time and metastable zone width, the mechanism and rate of nucleation, but also the kinetics of crystal growth [5][6][7][8][9]. Sonication also increases the repeatability which is one of its key advantages in comparison to conventional crystallization.…”