CN-121974808-A - Feedback control method for crystallization process of cyclopropylamine (R) -mandelate

CN121974808ACN 121974808 ACN121974808 ACN 121974808ACN-121974808-A

Abstract

The invention belongs to the technical field of automatic control, and discloses a feedback control method for a cyclopropylamine (R) -mandelate crystallization process, which comprises the steps of obtaining the concentration of cyclopropylamine (R) -mandelic acid in a solvent, the solvent temperature, the stirring speed and the pH value in real time, and forming a state parameter set reflecting the real-time state of a cyclopropylamine (R) -mandelate crystallization system; based on a state parameter set, the change rate of the supersaturation degree of the solute, the nucleation rate and the crystal growth rate are deduced by adopting an explicit dynamic relation to obtain a dynamic characteristic set of cyclopropylamine (R) -mandelate, the particle size, the shape and the crystallization uniformity of crystals are collected, a corresponding crystal quality prediction function is constructed by combining the dynamic characteristic set of cyclopropylamine (R) -mandelate to obtain a predicted crystal quality index, the actually detected crystal morphology index is compared with the predicted crystal quality index, the deviation is calculated, and the crystallization quality of cyclopropylamine (R) -mandelate is improved.

Inventors

QIAN JIANFENG
ZHANG ZHAOYONG
Zou Shichong
ZHANG CHAO

Assignees

巨野现代精细化工有限公司

Dates

Publication Date: 20260505
Application Date: 20251222

Claims (10)

1. A method for feedback control of a cyclopropylamine (R) -mandelate crystallization process, comprising: s1, acquiring the concentration of cyclopropylamine (R) -mandelic acid in a solvent, the temperature of the solvent, the stirring speed and the pH value in real time, and forming a state parameter set reflecting the real-time state of a cyclopropylamine (R) -mandelate crystallization system; s2, deriving a solute supersaturation degree change rate, a nucleation rate and a crystal growth rate by adopting an explicit dynamic relation based on a state parameter set to obtain a dynamic characteristic set of cyclopropylamine (R) -mandelate; S3, collecting the grain size, the shape and the crystallization uniformity of crystals, and constructing a corresponding crystal quality prediction function by combining the dynamic characteristic set of cyclopropylamine (R) -mandelate to obtain a predicted crystal quality index; s4, comparing the actually detected crystal morphology index with the predicted crystal quality index, and calculating to obtain a deviation amount; s5, applying the generated operation parameter correction amount to a crystallization kettle, and dynamically adjusting the temperature, stirring and solvent addition of cyclopropylamine and (R) -mandelate solution to form control of the cyclopropylamine (R) -mandelate crystallization process.
2. The feedback control method for cyclopropylamine (R) -mandelate crystallization process according to claim 1, wherein the method for obtaining in real time the concentration of cyclopropylamine (R) -mandelic acid in the solvent, the solvent temperature, the stirring speed and the pH value comprises: An immersed optical sampling probe with a fixed optical path is arranged in the reaction kettle, a reaction system is continuously scanned through a multi-wavelength absorption spectrum, and the instantaneous concentration of cyclopropylamine (R) -mandelic acid in a solvent is calculated in real time based on a pre-stored spectrum-concentration calibration model; the method comprises the steps of obtaining transient temperature data of a solvent by using a temperature sensor arranged on the wall of a reaction kettle, obtaining the stirring speed by measuring the stirring speed in real time by using a rotating speed sensor arranged on the driving end of a stirrer, and obtaining the pH value of a system by using an online pH electrode in direct contact with the reaction solvent.
3. The method for feedback control of a cyclopropylamine (R) -mandelate crystallization process according to claim 2, wherein the method for forming a state parameter set reflecting a real-time state of a cyclopropylamine (R) -mandelate crystallization system comprises: the method comprises the steps of adding an acquisition time stamp to the concentration of the cyclopropylamine (R) -mandelic acid in a solvent, the solvent temperature, the stirring speed and the pH value, and carrying out time synchronization processing; Performing a low-pass filtering process on the solvent temperature and the concentration of cyclopropylamine (R) -mandelic acid in the solvent in the instantaneous parameter set, performing a median filtering process on the stirring speed, and performing an exponential moving average process on the pH signal; And converting the synchronized and filtered instantaneous parameter set into multidimensional parameters reflecting the solvothermal state, the solute accumulation state and the fluid shearing state according to a preset mapping relation to form a state parameter set representing the real-time state of the cyclopropylamine (R) -mandelate crystallization system.
4. A method for feedback control of a cyclopropylamine (R) -mandelate crystallization process according to claim 3, characterized in that said method for obtaining a dynamic feature set of cyclopropylamine (R) -mandelate comprises: The instantaneous solute concentration, the solvent temperature and the pH value after the state parameter set synchronization and filtration are utilized, a preset solubility function is called to obtain equilibrium solubility, and the instantaneous supersaturation degree of the solute is calculated; substituting the instantaneous supersaturation degree, the solvent temperature and the shearing strength obtained by mapping the stirring speed into a preset nucleation dynamics model to obtain a corresponding instantaneous nucleation rate, and substituting the supersaturation degree, the solvent temperature and the crystal morphology feedback factor into a preset crystal growth dynamics model to obtain a corresponding instantaneous crystal growth rate; the nucleation dynamic model and the growth dynamic model are in explicit analytic forms, and finally the instantaneous supersaturation degree, the supersaturation degree change rate, the instantaneous nucleation rate and the instantaneous crystal growth rate are combined to form a dynamic characteristic set of cyclopropylamine (R) -mandelate.
5. The feedback control method for crystallization of cyclopropylamine (R) -mandelate salt according to claim 4, wherein said method for collecting crystal grain size, shape and uniformity of crystallization comprises: An on-line optical imaging unit is arranged on the side wall or the bottom of the crystallization kettle and is used for obtaining continuous microscopic images of the suspension crystal in a direct contact mode with the reaction solution, wherein the on-line optical imaging unit comprises an illumination light source, a microscopic imaging lens and an image sensor; Collecting a crystal image sequence with a time stamp by taking a sampling master clock as a trigger signal, performing light intensity equalization processing and background noise suppression processing on the collected crystal image sequence, and performing foreground segmentation based on edge gradients to extract crystal particles from a solution background; The shape of the single crystal grain comprises projection area, equivalent particle diameter, length-width ratio, roundness and angle distribution, and the particle diameter distribution width, shape dispersion and uniformity index of the crystal group are calculated based on the particle diameter and shape characteristics of all crystal grains at the same sampling time.
6. The feedback control method for cyclopropylamine (R) -mandelate crystallization process according to claim 5, wherein said predicted crystal quality index obtaining method comprises: Based on the acquired crystal grain size, shape and crystallization uniformity indexes, a corresponding crystal quality prediction function is constructed by combining a dynamic characteristic set of cyclopropylamine (R) -mandelate; The crystal quality prediction function combines the input crystal grain diameter, shape, crystallization uniformity index and the dynamics characteristic set of cyclopropylamine (R) -mandelate into a group of predicted crystal quality index through a multivariable nonlinear mapping mode.
7. The method for feedback control of a cyclopropylamine (R) -mandelate crystallization process according to claim 6, wherein said calculating a deviation amount comprises: and respectively acquiring crystal morphology indexes which are actually detected on line at the same sampling moment, carrying out one-to-one correspondence comparison on the actually detected crystal morphology indexes and the predicted crystal quality indexes according to the average particle size and the particle size distribution width, and obtaining the deviation value of each crystal quality characteristic by calculating the difference value of the actually detected crystal morphology indexes and the predicted crystal quality indexes.
8. The method for feedback control of a cyclopropylamine (R) -mandelate crystallization process of claim 7, wherein said method for generating an operating parameter correction comprises: Inputting the deviation amount of each crystal quality characteristic into a preset crystallization process control rule, wherein the crystallization process control rule is set according to the known dynamics relation among the supersaturation degree of solute, the nucleation rate, the crystal growth rate and the operation condition in a cyclopropylamine (R) -mandelate crystallization system; Determining the direction and degree of the deviation of the crystal quality from the target by judging the sign and the amplitude of the deviation, and determining a corresponding process adjustment strategy; When the average particle diameter deviation exceeds a preset average particle diameter deviation threshold, generating a correction amount for adjusting the solvent temperature, stirring speed or solvent addition amount according to a crystallization process control rule; when the deviation of the particle size distribution width exceeds a preset threshold value of the deviation of the particle size distribution width, a correction amount for adjusting the shearing condition or the crystallization cooling rate is generated according to the control rule, and finally, an operation parameter correction amount is formed.
9. The feedback control method of cyclopropylamine (R) -mandelate crystallization process according to claim 8, wherein said method of applying the generated correction amount of the operating parameter to the crystallization kettle comprises: and updating the real-time parameters of the corresponding control execution units in the crystallization kettle according to the correction amounts of the operation parameters, wherein the control execution units comprise a temperature control unit, a stirring control unit and a solvent adding control unit, and the system writes the correction amounts of the operation parameters into the corresponding control execution units.
10. A feedback control method for a cyclopropylamine (R) -mandelate crystallization process according to claim 9, characterized in that the method for forming the control of the crystallization process of cyclopropylamine (R) -mandelate salt comprises the following steps: The temperature control unit continuously adjusts heating or cooling power according to the operation parameter correction, the stirring control unit adjusts stirring rotation speed according to the operation parameter correction, and the solvent adding control unit controls intermittent or continuous adding speed of the solvent according to the operation parameter correction so as to change the supersaturation level of the system, thereby realizing control of the crystallization process of cyclopropylamine (R) -mandelate.

Description

Feedback control method for crystallization process of cyclopropylamine (R) -mandelate Technical Field The invention relates to the technical field of automatic control, in particular to a feedback control method for a cyclopropylamine (R) -mandelate crystallization process. Background Cyclopropylamine (R) -mandelate as an important organic salt compound has significant influence on downstream formulation performance in terms of crystal morphology, particle size distribution and purity. In the industrial crystallization process of organic salt compounds such as cyclopropylamine (R) -mandelate, the crystallization quality is often affected by the solute dissolution behavior, the supersaturation formation mechanism and the nucleation and crystal growth kinetics. Conventional crystallization process control techniques mostly rely on empirically set temperature profiles, fixed stirring strategies, or single concentration monitoring signals to guide the crystallization process, lacking the ability to identify real-time the true thermodynamic and kinetic states of the system. Because of the obvious coupling relation among the solvent temperature, the pH value, the stirring intensity and the instantaneous solute concentration, the prior art can not accurately describe the equilibrium solubility and the instantaneous supersaturation state of the solute under different operation conditions, so that the supersaturation amplitude, the accumulation speed and the change trend are difficult to effectively monitor. Under the condition of lacking accurate supersaturation degree information, the crystallization operation often cannot avoid the problems of sudden nucleation, excessive nucleation or crystal agglomeration in time, so that the crystal particle size distribution is difficult to keep stable. In addition, the conventional process cannot estimate key kinetic parameters such as nucleation rate and crystal growth rate in real time, so that dynamic unbalance between nucleation and growth is difficult to capture by a control system, and therefore, deviation of crystal size from a target interval, fluctuation of product purity or subsequent reduction of filtering performance is easily caused. Meanwhile, because the prior art lacks structural dynamic characteristic information, the temperature, stirring speed or solvent addition amount cannot be flexibly adjusted according to microscopic changes of the system, the feedback control effect is limited, and the stability and repeatability of the crystallization process are difficult to meet the requirement of industrial production. In view of the above, the present invention proposes a feedback control method for crystallization of cyclopropylamine (R) -mandelate salt to solve the above-mentioned problems. Disclosure of Invention In order to overcome the defects in the prior art and achieve the purposes, the invention provides a feedback control method for the crystallization process of cyclopropylamine (R) -mandelate, which comprises the following steps: s1, acquiring the concentration of cyclopropylamine (R) -mandelic acid in a solvent, the temperature of the solvent, the stirring speed and the pH value in real time, and forming a state parameter set reflecting the real-time state of a cyclopropylamine (R) -mandelate crystallization system; s2, deriving a solute supersaturation degree change rate, a nucleation rate and a crystal growth rate by adopting an explicit dynamic relation based on a state parameter set to obtain a dynamic characteristic set of cyclopropylamine (R) -mandelate; S3, collecting the grain size, the shape and the crystallization uniformity of crystals, and constructing a corresponding crystal quality prediction function by combining the dynamic characteristic set of cyclopropylamine (R) -mandelate to obtain a predicted crystal quality index; s4, comparing the actually detected crystal morphology index with the predicted crystal quality index, and calculating to obtain a deviation amount; s5, applying the generated operation parameter correction amount to a crystallization kettle, and dynamically adjusting the temperature, stirring and solvent addition of cyclopropylamine and (R) -mandelate solution to form control of the cyclopropylamine (R) -mandelate crystallization process. Preferably, the method for obtaining the concentration of the cyclopropylamine (R) -mandelic acid in the solvent, the solvent temperature, the stirring speed and the pH value in real time comprises the following steps: An immersed optical sampling probe with a fixed optical path is arranged in the reaction kettle, a reaction system is continuously scanned through a multi-wavelength absorption spectrum, and the instantaneous concentration of cyclopropylamine (R) -mandelic acid in a solvent is calculated in real time based on a pre-stored spectrum-concentration calibration model; the method comprises the steps of obtaining transient temperature data of a solvent by using a temperatu