Solute dissolution and diffusion parameter measurement system and measurement method

Abstract

The invention discloses a solute dissolution and diffusion parameter measurement system and method, and the system comprises a semiconductor laser, a light beam adjustment module, a liquid core column lens, an imaging device and a control device which are sequentially arranged. The light beam adjusting module is used for adjusting the monochromatic collimated light beam to obtain an incident light beam with a target width, a solution cavity of the liquid core column lens is formed between two negative meniscus column lenses of the liquid core column lens, and the solution cavity is used for injecting a target solvent after a target solute is placed at the bottom; the liquid core column lens is used for transmitting an incident light beam with a target width to the imaging device, so that the imaging device collects multiple frames of continuous dissolution and diffusion images of a target solute in the dissolution process of the target solute; and the control device is used for analyzing each frame of dissolution and diffusion image to obtain dissolution and diffusion parameters of the target solute in the target solvent. According to the scheme, the dissolution parameter measurement efficiency and accuracy are improved.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of solubility parameter measurement, and particularly relates to a solute solubility and diffusion parameter measurement system and a measurement method. BACKGROUND

[0002] Solid dissolving in liquid is a common physical phenomenon, and accurate measurement of the solubility and dissolution rate constant of solid in aqueous solution can provide basic data support for the study of physical and chemical processes, and there is a lack of relevant data for new drugs and materials in the pharmaceutical industry. For solid / semi-solid and suspension dosage form drugs, only the dissolved API (drug ingredient) can be finally absorbed by the human body, so the study of the solubility and dissolution rate constant of solid drug ingredients in aqueous solution can better understand the overall drug absorption in the biological system.

[0003] At present, the methods for measuring the solubility of solid include equilibrium method, kinetic method, potentiometric titration method, and thermal analysis method. However, these methods have problems such as large sample consumption, low automation level, and long determination time. The study of the solid dissolution process can only understand the solid dissolution process by measuring the changes of solid solute, solvent and solution before and after the experiment. The solid dissolution process studied by these methods is an invisible process.

[0004] The optical imaging through the liquid-core column lens can accurately analyze the dissolution process, and the dissolution process at each moment can be directly observed through the experimental image. At the same time, the solubility and dissolution rate constant can be calculated according to the dissolution image. The establishment of this method has very important academic significance and practical application value for the study of the dissolution behavior of solid solute. However, the optical measurement method is used to study the dissolution and diffusion process of solid solute, but due to the deflection of light when imaging through non-uniform medium, the calculation of "solubility and dissolution rate constant" will deviate. SUMMARY

[0005] In order to solve the problems in the prior art, the application provides a solute solubility and diffusion parameter measurement system and a measurement method to solve the problem of low accuracy of the solubility and diffusion parameter measurement in the prior art.

[0006] According to one aspect of the present application, a solute dissolution and diffusion parameter measurement system is disclosed, which comprises a semiconductor laser, a light beam adjustment module, a liquid core column lens, an imaging device and a control device arranged in sequence, the semiconductor laser is used to emit a monochromatic collimated light beam, the light beam adjustment module is used to adjust the monochromatic collimated light beam to obtain an incident light beam with a target width, the liquid core column lens is formed based on the combination of two opposite negative meniscus column lenses, a solution cavity of the liquid core column lens is formed between the two negative meniscus column lenses, and the solution cavity is used to place a target solute at the bottom and inject a target solvent; the liquid core column lens is used to transmit the incident light beam with the target width to the imaging device, so that the imaging device collects multiple continuous dissolution and diffusion images of the target solute during the dissolution process of the target solute; and the control device is used to analyze each frame of dissolution and diffusion image to obtain the dissolution and diffusion parameters of the target solute in the target solvent.

[0007] In some embodiments, the light beam adjustment module comprises an attenuation sheet, a spatial filter, a converging lens and a width limiting slit arranged in sequence, the attenuation sheet is used to attenuate the light intensity of the monochromatic collimated light beam to obtain an attenuated light beam, the spatial filter is used to filter stray light of the attenuated light beam to obtain a filtered light beam, the focusing lens is used to converge the filtered light beam to obtain a parallel light beam, and the width limiting slit is used to limit the width of the parallel light beam to obtain the incident light beam with the target width.

[0008] According to another aspect of the present application, a solute dissolution and diffusion parameter measurement method is also disclosed, which is performed based on the solid dissolution parameter measurement system of any one of the above, and the method comprises:

[0009] obtaining a target solvent concentration and a target dissolution and diffusion image of a target solute at a target time in the target solvent;

[0010] extracting a target dissolution and diffusion width in the target dissolution and diffusion image;

[0011] obtaining a refractive index linear relationship and a ray tracing equation;

[0012] constructing a deviation differential equation of light propagation in a non-uniform medium based on the refractive index linear relationship and the ray tracing equation;

[0013] determining a deflection value of the target solute in the target solvent at the target time based on the deviation differential equation, the deflection value being used to represent the deviation between a concentration calculation value and a concentration true value determined based on the target dissolution and diffusion image;

[0014] obtaining an expression of the dissolution and diffusion parameters of the target solute;

[0015] Based on the deflection value and the expression for the dissolution-diffusion parameter, the dissolution-diffusion parameter corresponding to the target solute is determined.

[0016] In some embodiments, constructing the deviation differential equation for ray propagation in a non-uniform medium based on the linear relationship of refractive index and the ray tracing equation includes:

[0017] Construct a concentration function expression;

[0018] Based on the concentration function expression, the refractive index linear relationship, and the ray tracing equation, the deviation differential equation for propagation in the non-uniform medium is derived; wherein, the concentration function expression is based on formula (1), the refractive index linear relationship is based on formula (2), and the ray tracing equation is based on formula (3).

[0019]

[0020] n(z,t)=p×C(z,t)+q (2);

[0021]

[0022] The deviation differential equations derived based on formulas (7) to (9) are as follows:

[0023]

[0024] In the formula, Used to characterize the amount of deflection that occurs during the propagation of light;

[0025] z represents the diffusion length of the solute concentration along the z-direction after dissolution and diffusion over time t.

[0026] p and q are both linear fitting coefficients for refractive index and concentration;

[0027] c0 is the initial concentration of the target solvent;

[0028] c s The saturation concentration of the target solute;

[0029] D0 is the diffusion coefficient of the target solute;

[0030] n0 is the initial refractive index of the target solvent;

[0031] erf is the error function;

[0032] t is the diffusion time of the target solute, which is determined based on the target time.

[0033] p is the fitting coefficient between refractive index and concentration; e is the exponential form;

[0034] The diffusion coefficient D0 is determined based on equation (1.1):

[0035]

[0036] In some embodiments, the construction concentration function expression comprises:

[0037] The Nernst-Brunner equation and the boundary condition of Fick's law are obtained;

[0038] Based on the Nernst-Brunner equation and the boundary condition of Fick's law, the concentration function expression is constructed in combination with Fick's law, wherein the Nernst-Brunner equation is represented based on equation (5), Fick's law is represented based on equation (6), and the boundary condition of Fick's law is represented based on equation (6.1):

[0039]

[0040]

[0041] wherein, is the dissolution rate at time t;

[0042] D is the diffusion coefficient of the target solute;

[0043] A is the solid-liquid contact area;

[0044] C(t) is the dissolution concentration at time t;

[0045] L is the diffusion length of the target solute in the target solvent;

[0046] V is the volume of the target solvent;

[0047] z is the diffusion length of the solute concentration along the z direction after dissolution and diffusion for t time.

[0048] In some embodiments, the determining the diffusion depth deflection value of the target solute in the target solvent at the target time based on the deviation differential equation comprises:

[0049] Solving the deviation differential equation;

[0050] Taking the value of the solved deviation differential equation as the diffusion depth deflection value of the target solute in the target solvent at the target time.

[0051] In some embodiments, the dissolution and diffusion parameters include solubility, the target time is the time corresponding to the dissolution equilibrium of the target solute, and the method further comprises:

[0052] obtaining a solubility formula;

[0053] determining solubility of the target solute based on the solubility formula and the dissolution saturation degree;

[0054] wherein the solubility formula is:

[0055] S=C S ×M×V (7);

[0056] wherein S is solubility, C S is saturation concentration, M is relative molecular mass of the target solute, and V is volume of the target solvent.

[0057] In some embodiments, the dissolution diffusion parameter further comprises a dissolution rate constant corresponding to the target solute, and the method further comprises:

[0058] determining the dissolution rate of the target solute based on a Noyes-Whitney dissolution equation;

[0059] wherein the Noyes-Whitney dissolution equation is:

[0060]

[0061] the integral formula is:

[0062]

[0063] wherein, is dissolution rate, and k is dissolution rate constant of the target solute;

[0064] B is intercept;

[0065] M max is maximum dissolution mass.

[0066] In some embodiments, the dissolution diffusion parameter further comprises dissolution amount at a target time, and the method further comprises:

[0067] determining the dissolution amount at the target time based on solute mass and solid-liquid contact area in combination with formula (10);

[0068]

[0069] wherein m is dissolved mass;

[0070] M is relative molecular mass of the target solute;

[0071] is integral of thin layer concentration C i along z direction.

[0072] The present application includes but is not limited to the following beneficial effects: the scheme combines liquid-core column lens optical imaging method and digital image processing technology, extracts and analyzes the features of the dissolution diffusion image, and reduces the error caused by light deflection through optical simulation, realizes the interdisciplinary modeling of optics and computer science, and then uses the modeling model after the interdisciplinary modeling to measure and correct the chemical data, and through the method, the dissolution diffusion parameters in the solid-liquid dissolution diffusion process can be more accurately measured. BRIEF DESCRIPTION OF DRAWINGS

[0073] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced as follows.

[0074] Figure 1 is a structural schematic diagram of a solute dissolution diffusion parameter measurement system of the embodiment of the present application;

[0075] Figure 2 is a structural schematic diagram of a liquid-core column lens of the embodiment of the present application;

[0076] Figure 3 is a flowchart of a solute dissolution diffusion parameter measurement method of the embodiment of the present application;

[0077] Figure 4 is a schematic diagram of a plurality of dissolution diffusion images of the embodiment of the present application;

[0078] Figure 5 is a potassium chloride dissolution schematic image of the embodiment of the present application;

[0079] Figure 6 is a potassium chloride dissolution simulation image of the embodiment of the present application;

[0080] Figure 7 is a D(C) relationship diagram of the embodiment of the present application;

[0081] In the figure, 1 is a semiconductor laser, 2 is an attenuating sheet, 3 is a spatial filter, 4 is a converging lens, 5 is a width limiting slit, 6 is a liquid-core column lens, and 7 is an imaging device. DETAILED DESCRIPTION

[0082] The terms "first", "second", "third", "fourth" and the like in the description and in the claims of the present application, if any, are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the use of these terms herein is to be construed to cover a non- exhaustive list, provided such distinction between the similar objects becomes relevant for explaining the subject matter embodied by any of the embodiments described herein. Furthermore, the terms "comprising", "having", "including", and the like, when used in the present specification, are used in their open-ended, non-limiting sense, for example, to mean that a process, method, system, product, or apparatus that "comprises", "has", or "includes" one step or unit can also comprise, have, or include additional steps or units not expressly mentioned or inherent to such process, method, system, product, or apparatus. The terms "plurality" and "a plurality" contained herein mean "two or more" unless expressly specified otherwise. The terms "plurality" and "a plurality" contain the term "plurality" mean "two or more" unless expressly specified otherwise.

[0083] For the sake of understanding, the specific flow of the embodiments of the present application is described below, in particular, Figure 1 As shown in the figure, a solute dissolution and diffusion parameter measurement system is disclosed, the system comprises a semiconductor laser 1, a light beam adjustment module, a liquid core column lens 6, an imaging device 7 and a control device arranged in sequence, the semiconductor laser 1 is used to emit a monochromatic collimated light beam, the light beam adjustment module is used to adjust the monochromatic collimated light beam to obtain an incident light beam with a target width, such as Figure 2 As shown in the figure, the liquid core column lens 6 is formed based on the combination of two opposite negative meniscus column lenses, a solution cavity of the liquid core column lens 6 is formed between the two negative meniscus column lenses, and the solution cavity is used to place the target solute at the bottom and inject the target solvent; the liquid core column lens 6 is used to transmit the incident light beam with the target width to the imaging device 7, so that the imaging device 7 collects a plurality of continuous dissolution and diffusion images of the target solute in the dissolution process of the target solute; and the control device is used to analyze each frame of the dissolution and diffusion image to obtain the dissolution and diffusion parameters of the target solute in the target solvent.

[0084] In some implementable schemes, the light beam adjustment module comprises an attenuation sheet 2, a spatial filter 3, a converging lens 4, a width limiting slit 5 arranged in sequence, the attenuation sheet 2 is used to attenuate the light intensity of the monochromatic collimated light beam to obtain an attenuated light beam, the spatial filter 3 is used to filter stray light of the attenuated light beam to obtain a filtered light beam, the converging lens is used to converge the filtered light beam to obtain a parallel light beam, and the width limiting slit 5 is used to limit the width of the parallel light beam to obtain the incident light beam with the target width.

[0085] Specifically, in the present example, a semiconductor laser 1 with a wavelength of 589 nm and a power of 20 mW can be selected. The spatial filter 3 is set to a 40 times microscopic objective lens + 15 μm pinhole, a converging lens 4 with a focal length of 500 mm, and a width adjustable width limiting slit 5. The imaging device 7 adopts a CCD camera with a resolution of 4090x3072 and a pixel size of 5.5 μm x 5.5 μm, and is placed at the focal plane position of the liquid core column lens 6.

[0086] Further, as shown in Figure 3 A solute dissolution diffusion parameter measurement method is disclosed, the method is performed based on the solid dissolution parameter measurement system of any one of the above, the method comprises:

[0087] S100, obtaining a target solvent concentration and a target solute dissolution diffusion image of a target time point of a target solute in a target solvent.

[0088] Specifically, a plurality of frames of dissolution diffusion images can be continuously obtained by the imaging device 7 every interval target time, in the example of the present application, the interval time can be 120S, so as to obtain a plurality of frames of continuous dissolution diffusion images at a plurality of time points, in the example of the present application, one frame of dissolution diffusion image at one time point is taken as an example to illustrate the method. Wherein, the target time point can be any time point in the plurality of time points. The target solvent can be pure water or ethanol, in the example, the target solvent is preferably pure water, and the target solute can be a substance to be measured, for example, it can be potassium chloride, sodium chloride and the like.

[0089] It can be understood that the target dissolution diffusion image obtained by the imaging device 7 is obtained after the light beam passes through the liquid core column lens 6. The liquid core column lens 6 is formed based on two negative meniscus column lenses. The curvature of the negative meniscus column lens determines the focal length. The greater the curvature, the shorter the focal length, and the smaller the image width on the focal plane. Curvature mismatch will cause aberration (such as coma, astigmatism), which will cause the edge of the diffusion image to diffuse (for example, when the curvature error is 10%, the image edge blur width increases by 2-3 pixels. Therefore, in one embodiment, before the light beam irradiation, the curvature can be simulated and optimized by optical software such as Zemax, so that the parallel light forms a sharp edge image with a line width ≤2 pixels on the focal plane after passing through the lens.

[0090] Further, the liquid core column lens 6 is formed by gluing two negative meniscus column lenses. If there is a large fluctuation on the gluing surface of the two lenses, it will cause a local refractive index mutation and form a false concentration gradient signal. In one example, an interferometer can be used to detect the flatness of the gluing surface, and a refractive index matching glue, such as NOA61, n = 1.52, can be used to reduce the interface reflection.

[0091] S102, extracting a target dissolution diffusion width in the target dissolution diffusion image.

[0092] It can be understood that, as Figure 4 to Figure 5As shown, the bright area (white cone-shaped part) in the figure represents the area of the solute dissolved and diffused: after the target solute is dissolved, the target solute molecules diffuse into the target solvent, forming a "concentration gradient area" - the closer to the bottom (the position of the solid), the higher the concentration; the higher, the lower the concentration. The uneven concentration causes the light to deflect (similar to "light passing through sugar water and bending"), and the deflected light is imaged on the CCD camera as a bright area. The width of the bright area reflects the range of the concentration gradient. The dark area in the figure is the solvent area / optical system background that is not affected by the diffusion of the solute. The dark area is the part of the target solvent that is not diffused by the target solute (or the area where the diffusion is very weak and the concentration can be considered as 0). These areas have weak refraction / scattering of light, and almost no light deflection enters the imaging system, so they appear as dark areas. It can also include the background noise of the optical system itself (such as the black base of the CCD camera).

[0093] Specifically, when extracting the width of the target solubility and diffusion, image analysis software such as a program based on MATLAB can be used to analyze the solubility edge position of each target solubility and diffusion image based on the bright and dark changes of the solubility and diffusion, measure the distance between these edges, and express it in pixel number or actual length (such as millimeters), denoted as image width W.

[0094] S104, obtaining a linear relationship of refractive index and a ray tracing equation.

[0095] Specifically, the linear relationship of the refractive index is the linear relationship between the refractive index and the concentration.

[0096] S106, constructing a deflection differential equation of the light propagation in the non-uniform medium based on the linear relationship of the refractive index and the ray tracing equation.

[0097] It can be understood that during the dissolution of the target solute in the target solvent, the solution concentration is uneven (the closer to the solid, the higher the concentration), and the light passing through will deflect like "the chopsticks inserted in the water and bent", resulting in an error in the extracted target solubility and diffusion width W (for example, the actual width is 10mm, and the extracted width from the image after deflection may be other values), therefore, it is necessary to determine how much width is deflected, and then subtract the deflected error from the original measured (based on image extraction) width W to obtain a more real width.

[0098] Specifically, the linear relationship of the refractive index can be expressed in combination with the concentration function expression, and step S106 can specifically include the following steps;

[0099] Step 1, constructing a concentration function expression.

[0100] Step 2, deriving a deflection differential equation of the light propagation in the non-uniform medium based on the concentration function expression, the linear relationship of the refractive index, and the ray tracing equation.

[0101] The concentration function expression is represented based on formula (1), the refractive index linear relationship is represented based on formula (2), and the ray tracing equation is represented based on formula (3).

[0102]

[0103] n(z,t)=p×C(z,t)+q (2);

[0104]

[0105] The deviation differential equation derived based on formulas (7) to (9) is as follows:

[0106]

[0107] In the formula, for representing the deflection amount of the light ray in the propagation process;

[0108] z is the diffusion length of the solute concentration along the z direction after the solute is dissolved and diffused for t time;

[0109] p and q are linear fitting coefficients of the refractive index and the concentration;

[0110] c0 is the initial concentration of the target solvent;

[0111] c s is the saturation concentration of the target solute;

[0112] D0 is the diffusion coefficient of the target solute;

[0113] n0 is the initial refractive index of the target solvent;

[0114] erf is an error function;

[0115] t is the diffusion time of the target solute, which is determined based on the time of the target moment;

[0116] p is a fitting coefficient of the refractive index and the concentration; and e is an exponential form;

[0117] The diffusion coefficient D0 is determined based on formula (1.1):

[0118]

[0119] Further, the construction of the concentration function expression can specifically include the following steps:

[0120] Step 11, obtaining the boundary conditions of the Nernst-Brunner equation and the Fick's law.

[0121] Step 12, based on the Nernst-Brunner equation and the boundary condition of Fick's law, the concentration function expression is constructed in combination with Fick's law.

[0122] Wherein, the Nernst-Brunner equation is expressed based on formula (5), the Fick's law is expressed based on formula (6), and the boundary condition of Fick's law is expressed based on formula (6.1):

[0123]

[0124] In the formula, is the dissolution rate at time t;

[0125] D is the diffusion coefficient of the target solute;

[0126] A is the solid-liquid contact area;

[0127] C(t) is the dissolution concentration at time t;

[0128] L is the diffusion length of the target solute in the target solvent;

[0129] V is the volume of the target solvent;

[0130] z is the diffusion length of the solute concentration along the z direction after dissolution and diffusion for t time.

[0131] S108, based on the deviation differential equation, the diffusion depth deflection value of the target solute in the target solvent at the target time is determined.

[0132] It can be understood that, in the scheme of the present application, in order to determine the deflected value, the deviation differential equation of light propagation in non-uniform medium can be constructed based on the linear relationship of refractive index and the ray tracing equation, and the deflection value is obtained by solving the deviation differential equation, so that the more realistic concentration distribution is obtained, and the dissolution mass is solved according to the concentration distribution obtained according to D(C) relationship.

[0133] S110, obtaining the dissolution and diffusion parameter expression of the target solute.

[0134] It can be understood that, in the process of dissolution of the target solute in the target solvent, the dissolution parameters representing the dissolution information include but are not limited to solubility, dissolution concentration, dissolution mass, dissolution rate constant and other information, and each dissolution parameter has a corresponding expression to solve the corresponding diffusion parameter.

[0135] S112, based on the deflection value and the dissolution and diffusion parameter expression, determining the dissolution and diffusion parameter corresponding to the target solute.

[0136] It can be understood that based on the above explanation, after eliminating the deflection value, the more real concentration, solubility and other dissolution parameters can be obtained based on the accurate value (obtained after eliminating the deflection value) combined with each dissolution and diffusion parameter expression. For example, if the deflection width is more than 0.5mm, the 10.5mm determined based on the image is corrected to 10mm, and the concentration is calculated again, the result is more accurate.

[0137] Specifically, in the present example, the dissolution and diffusion parameter can include solubility, and at this time, the deflection value and the dissolution and diffusion parameter expression in step S112 determine the dissolution and diffusion parameter corresponding to the target solute can be:

[0138] First, the solubility formula is obtained, and then the solubility of the target solute is determined based on the solubility formula and the dissolution saturation degree;

[0139] Wherein, the solubility formula is:

[0140] S=C S ×M×V (7);

[0141] In the formula, S is the solubility, C S is the saturation concentration, M is the relative molecular mass of the target solute, and V is the volume of the target solvent.

[0142] Further, the dissolution and diffusion parameter also includes the dissolution rate constant corresponding to the target solute, and at this time, the deflection value and the dissolution and diffusion parameter expression in step S112 determine the dissolution and diffusion parameter corresponding to the target solute can be:

[0143] Based on the Noyes-Whitney dissolution equation, the dissolution rate of the target solute is determined;

[0144] Wherein, the Noyes-Whitney dissolution equation is:

[0145]

[0146] The integral formula is:

[0147]

[0148] In the formula, is the dissolution rate, k is the dissolution rate constant of the target solute;

[0149] B is the intercept;

[0150] M max is the maximum dissolution mass.

[0151] Further, the dissolution and diffusion parameter also includes the dissolution amount at the target time, and at this time, the deflection value and the dissolution and diffusion parameter expression in step S112 determine the dissolution and diffusion parameter corresponding to the target solute can be:

[0152] The solubility at the target time is determined based on the solute mass and the solid-liquid contact area in combination with formula (10);

[0153]

[0154] In the formula, m is the dissolved mass;

[0155] M is the relative molecular mass of the target solute;

[0156] The concentration C of the thin layer is determined. i The integral along the z direction.

[0157] Specifically, the concentration distribution in the z direction is obtained by solving the analytical solution of the deviation differential equation of formula (10). The deflection value of the light propagation is obtained. Finally, D(C) is obtained according to the concentration distribution in the z direction in combination with formula (10), and the concentration distribution obtained according to D(C) is integrated to obtain the dissolved mass.

[0158] The scheme combines the liquid-core column lens 6 optical imaging method and the digital image processing technology, extracts and analyzes the features of the dissolution and diffusion image, and performs optical simulation to reduce the error caused by light deflection, realizes the interdisciplinary modeling of optics and computer disciplines, and then uses the modeling model after the interdisciplinary modeling to measure and correct the chemical data. Through this method, the dissolution and diffusion parameters in the solid-liquid dissolution and diffusion process can be measured more accurately.

[0159] For ease of understanding, the target solute is potassium chloride, the target solvent is pure water, and the imaging device 7 is a CCD.

[0160] 300 mg of KCl solid particles are placed at the bottom of the liquid-core column lens 6, and pure water is slowly injected at the upper part (to avoid disturbing the solid), forming a solid-liquid contact interface. The imaging device 7 is moved to the focal plane position of the liquid-core column lens 6. When a single liquid is injected, the CCD receives a fine and sharp straight line with the same width, i.e. the collimated light converges into a fine straight line after passing through the liquid-core column lens 6. With the continuous diffusion of the binary solution, different diffusion images are formed. The concentration near the solid interface is relatively large, which corresponds to the corresponding diffusion image. During the diffusion process, a concentration gradient is formed, and the corresponding refractive index is also different.

[0161] The imaging device 7 is connected through the control device, and in this program module, the "save the time interval of each dissolution diffusion image, and save the position" is set to collect multiple frames of dissolution diffusion images at multiple time points. After the image collection is completed, the image enters image processing, the image diffusion width position feature is extracted, and the width position is saved in real time. After the required dissolution diffusion width is determined, the concentration linear relationship is combined to obtain the dissolution diffusion concentration, Figure 5 is a frame of dissolution experiment image of potassium chloride.

[0162] Further, the solubility, dissolution rate constant and dissolution amount at the target time are determined according to the formulas (8) to (10) respectively. Taking the target time and the saturation concentration as an example, when the saturation concentration is reached, the maximum dissolution diffusion width at the dissolution equilibrium and the linear fitting relationship between the potassium chloride concentration and the refractive index are obtained:

[0163] C = 105.06 x n - 140.07 R 2 = 0.996

[0164] wherein R 2 represents the linear correlation;

[0165] The linear fitting relationship between the potassium chloride concentration and the width is:

[0166] C = 0.00542 x w - 0.0176 R 2 = 0.998

[0167] For example, at the initial stage of dissolution (which can be 0-10 minutes): the closer to the saturation concentration near the solid-liquid interface, the wider the image. The farther away from the interface, the lower the concentration, and the narrower the image. With the dissolution diffusion, the image gradually diffuses along the Z direction, and at this time, the image feature is that the bright area width increases rapidly from the initial W0 = 20 pixels (corresponding to C0 ≈ 0.1 mol / L) to W 10 = 80 pixels; concentration calculation: C 10 = 0.00542 x 80 - 0.0176 = 0.416 mol / L; the solid surface KCl dissolves rapidly, and the solute diffuses horizontally, forming a gradient zone with high concentration near the solid and low concentration far from the solid. The width increases rapidly, indicating that more solute diffuses in unit time, the dissolution rate dt / dc is large, which is consistent with the rule of "large Cs-C(t) difference, fast dissolution" in the Noyes-Whitney equation.

[0168] At the middle stage of dissolution (which can be 30-60 minutes): the width growth slows down, and at this time, the image feature is that the width increases from W 30 = 150 pixels to W 60 = 180 pixels (an increase of 30 pixels, only 37.5% of the initial stage); concentration calculation: C60 = 0.00542 x 180 - 0.0176 = 0.968 mol / L; Cs-C(t) difference is reduced, the solubility rate is reduced, and the solute diffusion range is expanded and slowed down. The width growth slows down, which directly reflects the physical process of "weakening of solubility driving force".

[0169] Dissolution equilibrium (after 60 minutes): width is stable, reflecting a solubility rate of zero, and the image characteristics at this time are W max = 700 ± 2 pixels, with a change rate of <1% for 30 consecutive minutes; concentration state: C(t) = Cs, dissolution-crystallization dynamic equilibrium, diffusion stops; measurement significance: stable width W max = 700 pixels corresponding to the saturation concentration, C max = 0.00542 x 700 - 0.0176 = 3.7764 mol / L Substituting into the solubility formula gives: S = 3.7764 x 74.55 x 0.01 = 28.15 g / 100 mL, i.e., 100 mL of water can dissolve a maximum of 28.15 g of KCl, which is consistent with the literature value (KCl solubility at 25°C is 28 g).

[0170] Through the width-concentration relationship, the optical signal is converted into diffusion parameters. Each 1-pixel width change corresponds to a concentration change, and the width increases from 20 pixels to 700 pixels, corresponding to a concentration increase from 0.1 mol / L to 3.7764 mol / L, reflecting the concentration accumulation caused by diffusion. The fitting of the width change rate and the solubility rate constant is linearly fitted with ln(Cs-C(t)) and time t, and combined with formulas (9) and (10), we can get:

[0171] ln(M max -m(t)) = kt + B, where M max is the maximum dissolution mass, and m(t) is the dissolution mass at time t. max = C S x M x S x L. m(t) is shown in Table 1. The maximum dissolution mass M max = 861.4836 mg, and the diffusion length L is 3 cm.

[0172] Table 1 Relationship between dissolution mass and time

[0173]

[0174] Combined with formula (9), the fitting of mass and time in Table 1, and the solubility rate constant determined by the dissolution mass obtained from the library dissolution image, the experimental value k = 0.90 x 10 -5 , the solubility mass determined by considering the deflection amount, the time k = 0.995 x 10 -5 , and the theoretical value k = 1.008 x 10 -5 under the D(C) system.

[0175] Further, in the examples of the present application, numerical simulation based on the dissolution and diffusion process is performed to obtain the simulation images of the dissolution and diffusion of potassium chloride as shown in FIG. 6, which is consistent with the schematic diagram of the dissolution of potassium chloride as shown in FIG. 5. Figure 6 Figure 5

[0176] In order to reduce the error caused by the deflection of light, D0is measured according to formula 7 and Figure Four D0= 1.79 x 10-5cm2 / s is obtained. D(C) is obtained according to the concentration distribution in the z direction, and the dissolution mass is obtained by integrating the concentration distribution obtained according to D(C). The diffusion coefficient varying with the concentration is obtained by the finite difference method, the distribution of the spatial concentration at different times is obtained, and the dissolution mass at different times is calculated according to D(C). D(C) = 1.79 x (1 + 0.1642 x C + 0.00831 x C2) x 10-5cm2 / s, and the relationship of D(C) is Figure 7 .

[0177] The above examples are only used to illustrate the technical solutions of the present application, but not to limit it; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that the technical solutions recorded in the foregoing examples can still be modified, or some technical features can be replaced by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application.​​

Claims

1. A solute dissolution and diffusion parameter measurement system, characterized in that, The system includes a semiconductor laser, a beam adjustment module, a liquid core lens, an imaging device, and a control device arranged sequentially. The semiconductor laser emits a monochromatic collimated beam. The beam adjustment module adjusts the monochromatic collimated beam to obtain an incident beam of the target width. The liquid core lens is formed by combining two opposing negative meniscus lenses, with a solution cavity between the two negative meniscus lenses. The solution cavity is used to inject the target solvent after placing the target solute at the bottom. The liquid core lens transmits the incident beam of the target width onto the imaging device, so that the imaging device can acquire multiple consecutive dissolution and diffusion images of the target solute during the dissolution process of the target solute. The control device is used to analyze each frame of the dissolution-diffusion image to obtain the dissolution-diffusion parameters of the target solute in the target solvent.

2. The solid dissolution parameter measurement system according to claim 1, characterized in that, The beam adjustment module includes an attenuator, a spatial filter, a converging lens, and a width-limiting slit arranged sequentially. The attenuator is used to attenuate the light intensity of the monochromatic collimated beam to obtain an attenuated beam. The spatial filter is used to filter stray light from the attenuated beam to obtain a filtered beam. The converging lens is used to converge the filtered beam to obtain a parallel beam. The width-limiting slit is used to limit the width of the parallel beam to obtain the incident beam of the target width.

3. A method for measuring solute dissolution and diffusion parameters, characterized in that, The method is performed based on the solid dissolution parameter measurement system according to any one of claims 1-2, and the method includes: Acquire the target solvent concentration and the target solute's dissolution-diffusion image in the target solvent at a target time; Extract the target dissolution-diffusion width from the target dissolution-diffusion image; Obtain the linear relationship of refractive index and the ray tracing equation; Based on the aforementioned linear relationship of refractive index and the aforementioned ray tracing equation, a deviation differential equation for the propagation of light in a non-uniform medium is constructed. Based on the aforementioned deviation differential equation, the deflection value at the target time when the target solute dissolves in the target solvent is determined. The deflection value is used to characterize the deviation between the calculated concentration value determined based on the target dissolution and diffusion image and the actual concentration value. Obtain the expression for the dissolution and diffusion parameters of the target solute; Based on the deflection value and the expression for the dissolution-diffusion parameter, the dissolution-diffusion parameter corresponding to the target solute is determined.

4. The method for measuring solute dissolution and diffusion parameters according to claim 3, characterized in that, The deflection differential equation for the propagation of light in a non-uniform medium, constructed based on the linear relationship of refractive index and the ray tracing equation, includes: Construct a concentration function expression; Based on the concentration function expression, the refractive index linear relationship, and the ray tracing equation, the deviation differential equation for propagation in the non-uniform medium is derived; wherein, the concentration function expression is based on formula (1), the refractive index linear relationship is based on formula (2), and the ray tracing equation is based on formula (3): n(z,t)=p×C(z,t)+q (2); The deviation differential equations derived based on formulas (7) to (9) are as follows: In the formula, Used to characterize the amount of deflection that occurs during the propagation of light; z represents the diffusion length of the solute concentration along the z direction after dissolution and diffusion over time t. p and q are both linear fitting coefficients for refractive index and concentration; c0 is the initial concentration of the target solvent; c s The saturation concentration of the target solute; D0 is the diffusion coefficient of the target solute; n0 is the initial refractive index of the target solvent; erf is the error function; t is the diffusion time of the target solute, which is determined based on the target time. p is the fitting coefficient between refractive index and concentration; e is the exponential form; The diffusion coefficient D0 is determined based on formula (1.1):

5. The method for measuring solute dissolution and diffusion parameters according to claim 1, characterized in that, The constructed concentration function expression includes: Obtain the boundary conditions of the Nernst-Brunner equations and Fick's law; Based on the Nernst-Brunner equation and the boundary conditions of Fick's law, and in conjunction with Fick's law, the concentration function expression is constructed; wherein, the Nernst-Brunner equation is expressed based on formula (5), Fick's law is expressed based on formula (6), and the boundary conditions of Fick's law are expressed based on formula (6.1): In the formula, Let be the dissolution rate at time t; D is the diffusion coefficient of the target solute; A represents the solid-liquid contact area; C(t) is the concentration of solution at time t; L is the diffusion length of the target solute in the target solvent; V is the volume of the target solvent; z represents the diffusion length of the solute concentration along the z-direction after dissolution and diffusion over time t.

6. The method for measuring solute dissolution and diffusion parameters according to claim 3, characterized in that, The determination of the diffusion depth deflection value at the target time when the target solute dissolves in the target solvent based on the deviation differential equation includes: Solve the aforementioned deviation differential equation; The value of the solved deviation differential equation is taken as the deflection value when the target solute dissolves in the target solvent at the target time.

7. The method for measuring solute dissolution and diffusion parameters according to claim 3, characterized in that, The dissolution-diffusion parameter includes solubility, the target time is the time corresponding to the dissolution equilibrium of the target solute, and the method further includes: Obtain the solubility formula; Based on the solubility formula and the solubility saturation, the solubility of the target solute is determined; The solubility formula is: S=C S ×M×V(7); In the formula, S is the solubility, and C is the solubility. S Where M is the saturation concentration, M is the relative molecular mass of the target solute, and V is the volume of the target solvent.

8. The method for measuring solute dissolution and diffusion parameters according to claim 3, characterized in that, The dissolution-diffusion parameters also include the dissolution rate constant corresponding to the target solute, and the method further includes: Based on the Noyes-Whitney dissolution equation, the dissolution rate of the target solute was determined; The Noyes-Whitney dissolution equation is as follows: The integral formula is: In the formula, Let be the dissolution rate, and k be the dissolution rate constant of the target solute; B is the intercept; M max This represents the maximum dissolved mass.

9. The method for measuring solute dissolution and diffusion parameters according to claim 3, characterized in that, The dissolution-diffusion parameters also include the amount of dissolution at the target time, and the method further includes: Based on the solute mass and the solid-liquid contact area, the amount of solubility at the target time is determined using formula (10). In the formula, m is the mass of dissolved; M is the relative molecular mass of the target solute; To determine the concentration C of the thin-layer chromatography system i Integral along the z-direction.

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