An evaluation method for direct compression suitability of traditional Chinese medicine extract powder

Abstract

An evaluation method for the direct compression adaptability of traditional Chinese medicine extract powder, which measures the particle size distribution, bulk density, tap density, Hausner ratio, Carr index, inter-particle porosity, angle of repose, moisture content and hygroscopicity of the traditional Chinese medicine extract powder, and obtains the true density; standardizes each index into a radius value set of 0-10 according to a preset conversion relationship, and constructs a physical fingerprint; calculates the parameter index, parameter profile index and good compressibility index to obtain a first determination; directly compresses the tablets without adding excipients, calculates the tensile strength and porosity of the tablets, and obtains a second determination based on the Ryshkewitch-Duckworth equation fitting; and outputs the direct compression adaptability conclusion by comprehensively considering the two types of determination results. The method realizes the quantitative correlation between powder characteristics and forming behavior, and can be used for direct compression process screening and quality control.

Description

Technical Field

[0001] This invention belongs to the field of powder engineering and pharmaceutical process evaluation technology of traditional Chinese medicine preparations, and relates to a method for evaluating the direct compatibility of traditional Chinese medicine extract powder. Background Technology

[0002] Traditional Chinese medicine extract powders are widely used in the preparation of solid dosage forms such as tablets. Direct compression molding (DCM) offers advantages such as a short process flow, low energy consumption, and high production efficiency, but it imposes stricter requirements on the flowability, packing properties, stability, and compressibility of raw and auxiliary powders. Due to the complex origins and diverse compositions of traditional Chinese medicine extract powders, their particle size distribution, moisture content, and hygroscopicity vary significantly. Furthermore, inter-particle friction, bridging, and agglomeration can easily lead to fluctuations in flowability. Simultaneously, the densification and binding abilities of the powders differ during tableting, easily resulting in problems such as insufficient tablet hardness, brittleness, poor formability, and large batch-to-batch variations. Existing evaluation methods often focus on single or a few indicators (such as angle of repose, Karl Fischer index, or hardness), lacking a unified quantitative evaluation framework that systematically correlates the multidimensional characteristics of powder science with tableting behavior and tablet quality indicators. This leads to inconsistent criteria for DCM suitability assessment, poor comparability of results, and hinders process screening and quality control. Summary of the Invention

[0003] The technical problem to be solved by this invention is to provide a method for evaluating the direct compression compatibility of traditional Chinese medicine extract powder. By constructing a powder properties fingerprint spectrum and quantifying it together with the tableting performance parameters, the method achieves standardized and traceable determination of the direct compression compatibility of traditional Chinese medicine extract powder, thus solving the problems of scattered evaluation dimensions, inconsistent standards, and difficulty in reflecting tableting behavior in the prior art.

[0004] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is: a method for evaluating the direct pressure compatibility of traditional Chinese medicine extract powder, wherein the method for evaluating the direct pressure compatibility of traditional Chinese medicine extract powder includes the following steps: S1. Sample Acquisition: Obtain samples of the Chinese herbal extract powder to be evaluated; S2. Powder Characterization: The powder characteristics of the traditional Chinese medicine extract powder samples were characterized to obtain a set of original values ​​for secondary indicators. The set of original values ​​for secondary indicators includes: median diameter. Particle size distribution width (Span), uniformity (Un), bulk density tap density Hausner ratio (HR), angle of repose (AR), and interparticle porosity The Cartesian index (CI), moisture content (MC), and hygroscopicity (H) were measured; and the true density was also determined. ; S3. Standardization and fingerprint construction: The original set of secondary indicators is converted into a set of radius values ​​from 0 to 10 according to a preset conversion relationship, and a physical fingerprint spectrum of the Chinese herbal extract powder sample is constructed based on the set of radius values. S4, SeDeM Index Quantification: Calculating Parameter Indexes Based on Radius Value Sets Parameter profile index With a good compressibility index And according to the parameter index Parameter profile index Good compressibility index Output the first direct voltage compatibility determination result; S5. Quantification of tablet compressibility: The traditional Chinese medicine extract powder sample is directly compressed into tablets, and the porosity of the tablets is measured. With the tensile strength of tablets And based on the Ryshkewitch–Duckworth equation, a system was established. With tablet porosity The fitting relationship is used to obtain the shapeability parameters. and And based on the tablet porosity Tablet tensile strength Output the second direct pressure compatibility determination result; S6. Comprehensive Output: The first direct pressure compatibility judgment result and the second direct pressure compatibility judgment result are used as a comprehensive basis to output the direct pressure compatibility evaluation result of the Chinese herbal extract powder sample.

[0005] The S1 mentioned above includes, S1.1 Drying into a dry extract: Drying the thick extract of traditional Chinese medicine into a dry extract; S1.2, Crushing and Sieving: The dry extract is crushed to obtain Chinese herbal extract powder; S1.3 Sealed storage: The sieved Chinese herbal extract powder is sealed and stored as a sample to be evaluated.

[0006] The S2 mentioned above includes, S2.1, Liquidity index measurement: Measurement of the angle of repose (AR); S2.2, Measurement and Derivation Calculation of Bulk Density: Measurement of Bulk Density With tap density and based on , Calculate the Karl index (CI), Hausner ratio (HR), and interparticle porosity. ; S2.3 True density determination: Determining the true density ; S2.4 Particle Size Distribution Measurement and Derivative Calculation: Measurement of particle size distribution parameters , , And calculate Span and uniformity Un based on particle size distribution parameters; S2.5, Moisture content determination: Determine the moisture content MC; S2.6, Hygroscopicity test: Measure the hygroscopicity H.

[0007] The S3 mentioned above includes, S3.1 Radius value conversion: Convert the radius value obtained in step S2 Particle size distribution width (Span), uniformity (Un), bulk density tap density Hausner ratio (HR), angle of repose (AR), and interparticle porosity The original values ​​of Karl index CI, moisture content MC, and hygroscopic rate H are converted into radius values ​​of 0 to 10 according to preset conversion relationships, forming a set of radius values; S3.2 Fingerprint mapping: Using the set of radius values ​​as the radii of each axis of the radar chart, construct the physical fingerprint of the Chinese herbal extract powder sample, and set the primary index corresponding to the physical fingerprint as uniformity, packing, flowability, compressibility, and stability.

[0008] The S4 includes: S4.1, Comprehensive Index Calculation: Calculate the parameter index based on the radius value set from step S3. Parameter profile index With a good compressibility index ; S4.2, First Direct Voltage Adaptability Determination: Based on Parameter Index Parameter profile index Good compressibility index Output the first direct voltage compatibility determination result; In S4.1, let the total number of secondary indicators involved in the calculation be... The number of secondary indicators with a radius value of not less than 5 is NP. Then the parameter exponent , And when hour, .

[0009] The S5 includes: S5.1 Direct compression: The traditional Chinese medicine extract powder sample is directly compressed into tablets without the addition of excipients; S5.2, Tablet Geometry and Mechanical Measurements: This includes measuring tablet hardness (F), tablet diameter (d), tablet thickness (t), and tablet mass. ; S5.3 Calculation of tablet quality parameters: Calculate the tensile strength of the tablet based on the measured tablet hardness F, tablet diameter d, and tablet thickness t. And based on tablet density and true density Calculate the solid fraction (SF) and tablet porosity. ; S5.4, Formability Fit and Second Judgment: Based on Tablet Tensile Strength With tablet porosity Establish the Ryshkewitch–Duckworth equation fitting relationship to obtain the shaping parameters. and Based on this, the second direct pressure adaptability judgment result is output.

[0010] S6 includes: outputting a physical fingerprint spectrum, a set of original values ​​for secondary indicators, a set of radius values, and parameter indices. Parameter profile index Good compressibility index Tablet tensile strength Solid fraction (SF) and tablet porosity , , The first direct pressure adaptability judgment result and the second direct pressure adaptability judgment result are used as a comprehensive basis to output the direct pressure adaptability evaluation result.

[0011] In step S2.1, the fixed funnel method is used to allow the sample to naturally accumulate and form a cone. The height of the cone is measured as h, and the radius of the base is measured as r. The angle of repose AR is then calculated using the following formula: ; In S2.4, the particle size distribution parameters were measured. , , And calculate the particle size distribution width Span according to the following formula: Span = , ; In S2.2, the sample is filled into the graduated cylinder and leveled, the sample mass m is recorded, and the following calculations are performed. ; Vibrate until the volume stabilizes and read the volume v after vibration, then calculate. ; and calculate , , ; In S2.6, a sample with a thickness of 2 mm is placed in a weighing bottle and dried for 24 hours before being weighed to obtain the mass. The mass of the weighing bottle is Subsequently, the mass was obtained by absorbing moisture and weighing. And calculate the moisture absorption rate according to the following formula. : .

[0012] The radius value in S3.1 is converted as follows: , ; ; ; .

[0013] In S5.3, the tensile strength of the tablet Tablet volume Tablet density solid fraction Tablet porosity ; In S5.4, the Ryshkewitch–Duckworth equation is: ; and based on tablet porosity The tablet tensile strength is at 25±5%. This serves as the second threshold for judging direct pressure adaptability.

[0014] The main beneficial effects of this invention are as follows: 1. This invention measures and standardizes secondary indicators such as particle size distribution, packing and flowability, moisture content and hygroscopicity into a set of radius values ​​from 0 to 10, and constructs a physical fingerprint spectrum. This achieves a unified characterization and visual comparison of the multidimensional properties of powder, and improves the consistency and comparability of the evaluation of different batches of samples. 2. This invention utilizes calculations... , , It also forms the first direct pressure compatibility judgment, achieving the effect of quantitatively classifying the direct pressure potential of powder with a clear calculation caliber, avoiding the deviation caused by relying on a single indicator; 3. This invention directly compresses tablets and calculates without adding excipients. and By combining the Ryshkewitch–Duckworth equation to obtain The second direct pressure compatibility criterion, formed with σmax, achieves the effect of establishing a quantitative correlation between powder characteristics and tableting behavior and tablet quality and conducting cross-validation, thereby improving the reliability and engineering applicability of the evaluation conclusions. Attached Figure Description

[0015] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0016] Figure 1 The physical fingerprint spectra of 12 kinds of traditional Chinese medicine extract powders of the present invention; Figure 2 This invention relates to 12 kinds of traditional Chinese medicine extract powders based on the Ryshkewitch–Duckworth equation. and tablets ; Figure 3 This invention relates to the cluster analysis of raw powders. Figure 4 This is the overall flowchart of the method for evaluating the compatibility of traditional Chinese medicine extract powder with direct compression according to the present invention; Figure 5 This is a flowchart of the secondary index measurement process of the present invention; Figure 6 The flowcharts for the conversion of secondary indicators and generation of physical fingerprint maps, and the flowcharts for index calculation and first determination of this invention are as follows: Figure 7 This is a flowchart of the tablet compressibility evaluation and second determination process of the present invention; Figure 8 This is a flowchart of the comprehensive judgment and output report generation process of this invention. Detailed Implementation

[0017] like Figures 1-8 middle, A method for evaluating the direct pressure compatibility of traditional Chinese medicine extract powder; I. ​​Symbol and parameter definitions (unified standards and traceability basis): To avoid the "sudden introduction" of parameters or symbolic ambiguity in subsequent steps, the parameters used in the evaluation system of this invention are first defined centrally. All measured values, calculated values, and output values ​​described in subsequent steps shall be based on the definitions in this section. 1) Particle size distribution parameters: : The particle size corresponding to a cumulative distribution of 10%; : The particle size (median diameter) corresponding to a cumulative distribution of particle size reaching 50%; : Particle size distribution when the cumulative distribution reaches 90%; Span: Particle size distribution width index, reflecting the degree of dispersion of particle size distribution; Un: Uniformity index, reflecting the degree of uniformity of particle size distribution.

[0018] 2) Parameters related to accumulation and flow. Bulk density is the apparent density of powder in its natural packing state. Tap density: Apparent density of powder after it has been tapped to a volume stable state; CI: Carr index: a dimensionless index characterizing the difference in packability / compressibility of powder; HR: Hausner ratio: a dimensionless index characterizing the flowability of powder. : Interparticle porosity, a characterization index of packing voids derived from bulk density and tap density; AR: Angle of repose, an angular index characterizing powder flowability.

[0019] 3) Stability-related parameters: MC: moisture content, reflecting the moisture content of the powder; H: moisture absorption rate, reflecting the degree of moisture absorption of the powder under specified temperature and humidity conditions (expressed as a percentage).

[0020] 4) Parameters related to density, tableting and formability : True density; F: Crushing force obtained from tablet hardness test; d: Tablet diameter; t: Tablet thickness; Tablet quality; Tablet volume; Tablet density; Tablet tensile strength; SF: solid fraction; Tablet porosity; , : The forming parameters obtained from the Ryshkewitch–Duckworth fitting equation, where Used to characterize the strength of adhesive ability. Used to characterize the theoretical ultimate tensile strength when the porosity approaches 0.

[0021] 5) SeDeM index related parameters, : No. Standardized radius values ​​(range 0-10) of each secondary indicator; The total number of secondary indicators, as determined by this invention. ; The number of secondary indicators with a radius value of not less than 5; : Parameter index; : Profile index; Good compressibility index; : Credibility factor, when Time to take Note: The above symbol definitions are used to ensure that the entire process of "measurement-calculation-judgment-output" has a consistent standard, and that any output result can be traced back to the corresponding original measured value and formula calculation link.

[0022] Step S1: Sample preparation. The purpose of step S1 is to obtain the sample to be evaluated under uniform drying, particle size and storage conditions to ensure that the subsequent powder science indicators and tablet evaluation results are comparable.

[0023] S1.1 Drying to a dry extract: Place the thick extract of traditional Chinese medicine in an electrically heated drying oven and dry it to a dry extract at 60°C. This step is used to transform the sample from a viscous system into a pulverizable and sieveable solid state, avoiding distortion of subsequent particle size and packing indices due to differences in sample state.

[0024] S1.2 Crushing and Sieving: The dry extract is crushed and then passed through a No. 4 sieve with a mesh size of 250 μm ± 9.9 μm (65 mesh) to obtain the herbal extract powder. This step is used to standardize the upper limit of sample particle size and particle size aperture, providing a preliminary basis for the comparability of indicators such as particle size distribution parameters, bulk density / tapered density, etc.

[0025] S1.3 Sealed Storage: After sieving, the herbal extract powder is sealed and stored in an electronic dehumidifier as a sample to be evaluated. This step is used to reduce the disturbance of environmental humidity fluctuations on the moisture content (MC), hygroscopicity (H), and flowability / stacking properties, ensuring that the evaluation results are traceable and stable.

[0026] Step S2: Powder properties characterization. Step S2 is used to construct the original set of secondary index values ​​and obtain the true density. To facilitate review and reproduction, this step describes each indicator in the format of "Measurement Method - Raw Data - Calculation Formula - Unit / Scope", and ensures that the data input required for subsequent S3 standardization and S4 index calculation comes from the output of this step.

[0027] S2.1 Angle of Repose (AR) (flowability index), measurement method: using a fixed funnel method to allow powder to naturally accumulate and form a cone; raw data: measured cone height. With the base radius ; Calculation formula: Unit / caliber: Angle indicator; , A consistent unit of length is used; this index is used to characterize the flow and accumulation behavior of powders under conditions without external force.

[0028] S2.2 Bulk Density tap density and derived indicators CI, HR, (Related to stacking properties / compressibility / flowability), Measurement method: Freely fill a 25 mL graduated cylinder with the sample and level it, recording the sample mass; tap the graduated cylinder until the volume stabilizes, then read the volume; Raw data: Sample mass Volume after vibration ; Calculation formula: Bulk density: Tap density: Cartesian index: Houser ratio: Interparticle porosity: Unit / caliber: , It has the dimension of density; , , It is a dimensionless index; among which and It focuses more on reflecting the compressibility and porosity characteristics of the powder's packing structure. It is used in conjunction with AR for liquidity-level explanations.

[0029] S2.3 True Density (Density Standard), Measurement Method: Determine the true density of the sample. Raw data: True density measurement; Unit / caliber: As a subsequent tablet solid fraction SF and porosity The calculated density baseline ensures that the calculation of "tablet structure parameters" has a traceable physical reference.

[0030] S2.4 Particle size distribution and derived indices Span and Un (uniformity indices), measurement method: measure the particle size distribution parameters. , , Raw data: , , Their statistical meanings are the particle sizes corresponding to cumulative distributions reaching 10%, 50%, and 90%, respectively; calculation formula: , Unit / caliber: , , A consistent unit of length is used; Span and Un are dimensionless; this set of indicators is used to reflect the influence of powder particle size uniformity on packing, flow and tableting behavior.

[0031] S2.5 Moisture content MC (stability index), determination method: determine the moisture content of the sample; raw data: moisture content measurement reading; unit / caliber: MC is one of the components of the primary stability index, used together with hygroscopicity H to reflect the moisture state and environmental sensitivity of the sample, thereby explaining the possible sources of fluctuations in powder flowability and tableting properties.

[0032] S2.6 Moisture Absorption Rate H (Stability Index), Measurement Method: Place a 2 mm thick sample in a weighing bottle and dry for 24 h before weighing; place the sample at 25℃ and 80% RH to absorb moisture and then weigh; Raw Data: Weighing bottle mass Quality of "bottle + sample" after drying Quality of "bottle + sample" after moisture absorption ; Calculation formula: Unit / Diameter: H is expressed as a percentage; This index reflects the powder's response to environmental humidity, providing a stability dimension to support the interpretation of flowability and tableting performance results. At this point, step S2 outputs the complete set of original values ​​for secondary indices and true density. And it serves as the sole input source for the standardization process in step S3.

[0033] Step S3: Standardization and physical fingerprint map construction. The purpose of step S3 is to eliminate the differences in the dimensions of different secondary indicators, so that each indicator can be comprehensively compared on the same scale, and realize the visualization and structured interpretation in the form of fingerprint map.

[0034] S3.1 Radius Value Conversion: The original values ​​of the secondary indicators obtained in S2 are converted into a set of radius values ​​according to a preset conversion relationship, specifically as follows: ; , ; , , ; Among them, the radius value The physical meaning is "the score intensity of the secondary indicator on a unified evaluation scale", which is used for subsequent index calculation and fingerprint mapping.

[0035] S3.2 Fingerprint Mapping and Primary Index Interpretation Framework: Using 11 radius values ​​as the axes of the radar chart, these values ​​are arranged in a fixed order and plotted to obtain the physical fingerprint of the traditional Chinese medicine extract powder sample. To achieve "interpretable" structured analysis, the primary indices are set as: homogeneity, packing density, flowability, compressibility, and stability. The changes in the length of each axis radius in the fingerprint chart directly reflect the sample's strengths and weaknesses in the corresponding dimensions, thus providing an interpretive basis for subsequent index determination and tableting verification.

[0036] Step S4: SeDeM Index Calculation and First Direct Pressure Compatibility Determination: Step S4 calculates the SeDeM index based on the radius value set from Step S3. , , This results in the first direct pressure compatibility assessment. This assessment is a quantitative output at the "powder properties level" and is used to evaluate the direct pressure potential of the sample from a multi-dimensional perspective.

[0037] S4.1 Parameter Index Among the 11 radius values, those that satisfy the following conditions are considered: The number of indicators is NP, and the total number of secondary indicators is ,but: ,in, The coverage ratio of secondary indicators used to characterize samples at a "basically acceptable level" reflects the overall compliance of powder science.

[0038] S4.2 Parametric Profile Index Average all radius values: ,in, It is used to reflect the average level of the overall physical state of a sample on a uniform scale.

[0039] S4.3 Good compressibility index , among which when Time to take .based on , , The first direct voltage adaptability determination result is generated and used as one of the inputs to the comprehensive output of step S6.

[0040] Step S5: Quantification of tableting formability and determination of compatibility with the second direct compression method. Step S5 involves direct tableting under the condition of "no added excipients" and determining the compatibility based on "porosity". —Tensive strength "Relationship fitting to obtain shaping parameters" , This results in the second direct compression compatibility assessment. This assessment is a quantitative output of the "compression behavior / tablet quality level," complementing and cross-validating step S4.

[0041] S5.1 Direct tableting without excipients: The herbal extract powder sample obtained in step S1 is directly compressed into tablets without the addition of excipients. This setting is used to avoid the masking of the binding and densification behavior by excipients, so that the evaluation results can reflect the direct compression molding capability of the sample itself.

[0042] S5.2 Acquisition of raw tablet test data: The following parameters were measured on the obtained tablets: tablet hardness F, tablet diameter d, tablet thickness t, and tablet mass. Where F, d, and t are used to calculate tensile strength. , d and t are used to calculate tablet volume and density, and then to correlate with true density. Porosity obtained through linkage This ensures a closed-loop data chain between S2.3 and S5.

[0043] S5.3 Calculation of tensile strength, solid fraction and porosity, tensile strength of tablets: Tablet volume: Tablet density: In some embodiments, considering that the tablet shape may be biconvex, concave, or have rounded corners, the tablet volume... The calculation is based on the surface parameters of the punch used and the geometry of the tablet, where the surface parameters of the punch are obtained from the specifications of the punch used or the equipment configuration parameters.

[0044] Solid fraction and porosity: , ;in, The true density obtained in step S2.3; thus ensuring It has a clear physical meaning and a traceable origin. S5.4 Ryshkewitch–Duckworth Fitting and Second Decision: Establishing the Fitting Equation: ;pass and The fitting obtained and And using the tablet production baseline as the second judgment threshold: when At 25±5% and When the tablet formability baseline is met, the second direct pressure compatibility determination result is output.

[0045] Step S6: Comprehensive Output and Traceability of Evaluation Results: Step S6 is used to combine the "first judgment at the powder science level" and the "second judgment at the tableting formability level" into a single output, so that the final evaluation results are supported by both a multi-dimensional index system and direct tableting test verification, thereby improving the reliability of the conclusions and their engineering usability.

[0046] S6.1 Output List (Unified Delivery Standard), the final output of this invention shall include at least the following: (1) Set of original values ​​and true density of secondary indicators (2) Radius value set and physical fingerprint spectrum; (3) SeDeM index , , and the first judgment result; (4) Tablet calculation parameters , , With fitted parameters , and the second judgment result; (5) Comprehensive direct pressure adaptability evaluation result.

[0047] S6.2 Traceable Link Description (Closed Loop): Any SeDeM index result can be traced back to the radius value. Further back to the original measured values ​​of each secondary index in S2; any porosity With tensile strength All can be traced back to the original measured values ​​of the tablet. , , , and through true density The results were traced back to the S2.3 measurement; the final comprehensive conclusion was supported by the first and second judgments, forming a reproducible closed loop of "indicator system - tableting verification - comprehensive judgment".

[0048] Example 1: Evaluation of the direct compression compatibility of 12 kinds of traditional Chinese medicine extract powders I. Instruments and Materials, 1. Instruments: HS-88-118 multi-functional dryer (Ruian Hongsheng Food Machinery Factory), 101-3S electric heating blast drying oven (Shanghai Qiuzuo Scientific Instrument Co., Ltd.), HC103 moisture analyzer, ZKZMD-10 true density analyzer (Beijing Zhongke Micro-Nano Precision Instrument Co., Ltd.), CTB540FD electronic dehumidifier (Shenzhen Aiteer Electronic Technology Co., Ltd.), LHH-150GSP comprehensive drug stability test chamber (Shanghai Yiheng Scientific Instrument Co., Ltd.), ST-Z16 physical property analyzer, ZP-18 rotary tablet press (Shanghai Tianhe Pharmaceutical Machinery Co., Ltd.), pulverizer, and particle size analyzer were used.

[0049] 2. Materials: Aqueous extracts of Angelica sinensis and Paeonia lactiflora for promoting blood circulation, Angelica sinensis for relaxing muscles and tendons, Angelica sinensis for promoting blood circulation, Rehmannia glutinosa for strengthening muscles and tendons, Morus alba for relieving numbness, Angelica pubescens for removing dampness, Prunus persica for reducing swelling, Rehmannia glutinosa for strengthening bones, Astragalus membranaceus for eliminating dampness, Angelica sinensis and Ligusticum striatum for nourishing bones, Pueraria lobata for removing dampness, and Paeonia lactiflora for removing blood stasis, labeled as samples 1-12 respectively.

[0050] II. Experimental methods, step S1: Preparation of Chinese herbal extract powder: The thick extract of Chinese herbal medicine was placed in an electric heating drying oven and dried at 60°C until it became a dry extract, which was then pulverized; the pulverized dry extract was passed through a No. 4 sieve (250 μm±9.9 μm, 65 mesh) to obtain compound Chinese herbal extract powder; the obtained Chinese herbal extract powder was sealed and stored in an electronic dehumidifier for later use.

[0051] Step S2: Characterization of the properties of traditional Chinese medicine powders (acquisition of raw data for secondary indicators); To facilitate data traceability, the symbols used in this step are standardized as follows: v is the mass of the powder; h is the volume after compaction; r is the height of the stacking cone; and r is the radius of the base of the stacking cone. For the mass of the weighing bottle; The total mass of the weighing bottle and the sample after drying for 24 hours; The total mass of the weighing bottle and the sample after 24 hours of moisture absorption; , , For particle size statistics; F is the tablet crushing force; d is the tablet diameter; t is the tablet thickness; mp is the tablet mass. ρ is the true density; ρp is the tablet density; SF represents the tensile strength of the tablet; SF represents the solid fraction. Porosity.

[0052] S2.1 Angle of repose AR: The angle of repose AR is determined using the fixed funnel method: A culture dish with a known conical base radius r is used as the base. The sample is allowed to pass freely through the fixed funnel to form a stacked cone on the base. The height h of the cone is measured, and the angle of repose AR is calculated according to formula (1-1): Formula (1-1) (Note: AR classification can be used as a commonly used liquidity reference, but is not a necessary limiting condition for the evaluation system of this invention).

[0053] S2.2 Bulk Density tap density Karl index (CI), Hausner ratio (HR), and interparticle porosity Weigh a 25 mL graduated cylinder beforehand and tare it. Fill the cylinder with the sample to be tested, and level it with a scraper after filling. Weigh the sample mass m. Calculate the bulk density ρb using formula (1-2). Then, continuously press down on the sample to compact it until the volume no longer changes. Read the volume v of the powder in the graduated cylinder at this point. Calculate the tapped density using formula (1-3). And calculate CI, HR and respectively according to formulas (1-4) to (1-6). : , formula (1-2); , formula (1-3); , formula (1-4); , formula (1-5); , formula (1-6).

[0054] S2.3 True Density True density was determined using a true density analyzer. Each sample was cycled three times and the average was taken.

[0055] S2.4 Particle size and particle size distribution: Measurement was performed using a dry laser particle size analyzer module: The sample was added to the metal tank of the sampler, and the measurement was performed and recorded according to the preset SOP. , , Calculate the particle size distribution width Span and uniformity Un using formulas (1-7) and (1-8); repeat three times for each sample: Span = , formula (1-7); , formula (1-8).

[0056] S2.5 Moisture content MC: Moisture content MC was determined using an infrared rapid moisture analyzer: about 1 g of sample was evenly spread on a weighing pan and the temperature was set to 105℃; when the moisture content did not change within 30 s, the MC was read; each sample was measured three times and the average was taken.

[0057] S2.6 Moisture Absorption Rate H: Add a sample of approximately 2 mm thickness to a weighing bottle, place it in a desiccator and dry for 24 h to remove as much moisture as possible. Weigh the total mass after drying (m2) and record the mass of the weighing bottle (m1). Transfer the weighing bottle to a comprehensive drug stability test chamber and allow it to absorb moisture at 25℃ and 80%RH. Weigh the total mass after moisture absorption (m3) at different time points. Calculate the 24-h moisture absorption percentage H using formula (1-9): , formula (1-9); Step S3: Comprehensive evaluation of direct pressure performance and establishment of physical fingerprint spectrum (radius value set and radar chart, Figure 1 The physical properties of traditional Chinese medicine extract powder are characterized by five primary indicators: uniformity, bulking capacity, compressibility, flowability, and stability. Secondary indicators are selected and corresponding to the following: Uniformity: Span, Un; Stacking property: , Compressionability: CI, Liquidity: HR, AR; Stability: MC, H. The above 11 secondary indicators were normalized according to the numerical ranges and conversion methods listed in Table 3, converting each secondary indicator to a radius value between 0 and 10, forming a set of radius values; a radar chart of the physical fingerprint spectrum was drawn based on the set of radius values, see... Figure 1 .

[0058] Step S4: / / Calculate the compatibility with the first direct pressure and construct the parameter index based on the radius values ​​of the 11 secondary indicators obtained in step S3. Parameter profile index With a good compressibility index : Equation (1-14); where NP is the number of parameters with a radius value ≥ 5, and NPt is the total number of test parameters (NPt = 11 in this embodiment). Equation (1-15), where ri is the radius value of the i-th secondary index. Equation (1-16), where f is the confidence level of the factor, and when the number of parameters is 11, The first rule for determining DC voltage compatibility is as follows: If both conditions are met >0.5 >5 and If the value is greater than 5, the powder is considered suitable for direct tableting. like >0.5 and and If the value is between 3 and 5, it indicates that auxiliary materials need to be added to compensate for the deficiency before direct pressing; if >0.5 and and If all values ​​are less than 3, it indicates that the powder cannot be directly compressed. Appropriate excipients can be added and wet or dry granulation can be used before tableting.

[0059] Step S5: Evaluation of tablet-related properties and formability (second direct compression compatibility determination); S5.1 Tableting and Basic Parameter Determination: Tablets were obtained by directly compressing 500 mg of the corresponding powder using a tableting machine, without adding any excipients. The filling thickness was kept constant at 5.05 mm. Tablets of different thicknesses were compressed by adjusting the tablet thickness, with 3 tablets compressed for each thickness and each material. Tablet mass was then determined. The tablet diameter d and thickness t are measured using vernier calipers, and the tablet volume is calculated. And obtain tablet density .

[0060] The tablet hardness F was determined using a texture analyzer. The specific operating conditions were: trigger force 5.0 g, deformation 2.000 mm, and testing speed 80 mm / min. The tablet was placed under a P / 36R probe for testing. The hardness F was calculated using formulas (1-10) to (1-12). SF and : , formula (1-10); , formula (1-11); Formula (1-12), where, For tablet density, This is the true density of the material.

[0061] S5.2 Formability Fit (Ryshkewitch–Duckworth Equation): The Ryshkewitch–Duckworth equation is used to evaluate the formability of materials. The equation is as follows: Formula (1-13); where, For tablet porosity, for →The theoretical ultimate tensile strength of the tablet at 0. Let be a constant representing the adhesive strength.

[0062] S5.3 Second direct pressure compatibility judgment baseline: when the tablet porosity Within the range of 25±5% and the tablet tensile strength If the value is ≥2, the tablet production baseline is considered to be met; otherwise, the tablet production baseline is considered not to be met.

[0063] Step S6: Comprehensive Output. Combining the first judgment result of Step S4 and the second judgment result of Step S5, output the direct pressure compatibility evaluation conclusion for each sample; the output includes at least: the original powder science measurement results shown in Tables 1 and 2, the conversion method of secondary indexes shown in Table 3, and the set of radius values ​​of secondary indexes shown in Table 4. Figure 1 The physical fingerprint spectrum shown, the primary indicators shown in Table 5, and / / result, Figure 2 The results of the shape fit and the second judgment conclusion are shown in Table 6.

[0064] III. Results (Compared with Tables 1 to 6) Figures 1-2 (One-to-one correspondence) 3.1 Powder flowability: The flowability of traditional Chinese medicine extract powders was characterized by the angle of repose (AR), Karl Fischer index (CI), and Hausner ratio (HR). The results showed that the AR values ​​of the 12 traditional Chinese medicine extract powders ranged from 46.48 to 56.88°; the CI values ​​ranged from 23.87 to 37.47; and the HR values ​​ranged from 1.31 to 1.60. Overall, except for sample 4, which had relatively low CI and HR, the flowability indicators of the other samples were generally high, indicating that most samples had poor flowability. The results of the basic powder properties are shown in Table 1.

[0065] Table 1. Basic Powder Properties of Traditional Chinese Medicine Powders (x±s, n=3)

[0066] Table 2. Basic Powder Properties of Traditional Chinese Medicine Powders (x±s, n=3)

[0067] 3.2 Comprehensive Evaluation of Powder Direct Compression Performance and Establishment of Physical Fingerprint: To comprehensively characterize the physical quality properties of traditional Chinese medicine extract powder, a powder physical fingerprint was constructed. Powder properties were characterized from five aspects: uniformity, packability, compressibility, flowability, and stability, which were used as primary indicators. Eleven secondary indicators were selected, among which the median diameter D0.5 was also denoted as D50, which uses the same statistical caliber as D50 in Table 2.

[0068] The correspondence between secondary and primary indicators is as follows: Uniformity: Span, Un; Stacking property: , Liquidity: HR, AR; Compressibility: CI; Stability: MC, H.

[0069] Because the secondary indicators have different dimensions, they are normalized. According to the numerical ranges and conversion formulas listed in Table 3, the 11 secondary indicators are converted to radius values ​​between 0 and 10. These radius values ​​are then displayed as a radar chart to obtain the physical fingerprint spectrum. Figure 1 .

[0070] Based on the radius values ​​of 11 secondary indicators, a parametric index is constructed. Parameter profile index With a good compressibility index Based on this, the first direct voltage adaptability determination is made: when the following conditions are met simultaneously... >0.5 >5 and When >5, the powder is deemed suitable for direct tableting; when >0.5 and and When the value is between 3 and 5, it indicates that auxiliary materials need to be added to compensate for the deficiency before direct pressing; when >0.5 and and When all values ​​are <3, it indicates that the powder is not suitable for direct compression. Appropriate excipients can be added and wet or dry granulation can be used before tableting.

[0071] As can be seen from the results in Table 5, the 12 samples and All values ​​were less than 5, indicating poor compressibility, but performance could be improved by adding suitable excipients. Except for sample 4, whose flowability index was greater than 5, the other samples had values ​​below 5 in stability, flowability, and compressibility, indicating that stability, flowability, and compressibility are important factors affecting the direct compression of traditional Chinese medicine extract powder into tablets. Table 3 shows the conversion methods for 11 indicators in the SeDeM expert system (Note: ν represents the corresponding parameter in the conversion formula).

[0072] Table 4. Conversion results of secondary indexes of traditional Chinese medicine powder based on the SeDeM system

[0073] Table 5. Conversion results and parameter results of primary indicators of traditional Chinese medicine powder based on the SeDeM system.

[0074] 3.3 Formability evaluation: Direct compression is a simple process that does not introduce additional moisture, but it requires high powder flowability and compressibility. Tablet tensile strength. With porosity It varies with molding conditions; suitable porosity is beneficial for tablet disintegration, and tensile strength reflects the mechanical strength of the tablet. The production baseline can be used as a second criterion for determining direct compression compatibility: when the porosity... Within the range of 25±5% and tensile strength When the value is ≥2, the tablet production baseline is considered to be met.

[0075] The formability of 12 kinds of traditional Chinese medicine extract powders was evaluated based on the Ryshkewitch–Duckworth equation. (See...) Figure 2 Compared with Table 6. The results show that, under direct compression conditions, samples 2 and 8, when It can be achieved when it is in the range of 25±5%. The production baseline was ≥2; the remaining 10 samples were difficult to reach the minimum tensile strength baseline during direct tableting, resulting in poor formability. Furthermore, and It is negatively correlated. When the tensile strength cannot meet the production baseline, the tensile strength can be improved by applying greater pressure to reduce the tablet porosity.

[0076] Figure 2 Twelve kinds of Chinese herbal extract powders based on the Ryshkewitch–Duckworth equation and tablets Note: Generally, actual tablet production needs to meet the following requirements. When within the range of 25±5%, ≥2.

[0077] Table 6. Fit of the Ryshkewitch–Duckworth equation

[0078] The above embodiments are merely preferred technical solutions of the present invention and should not be considered as limitations on the present invention. The embodiments and features described in these embodiments can be arbitrarily combined without conflict. The scope of protection of the present invention should be limited to the technical solutions described in the claims, including equivalent substitutions of the technical features described in the claims. That is, equivalent substitutions and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. A method for evaluating the direct compression compatibility of traditional Chinese medicine extract powder, characterized in that, The method for evaluating the direct pressure compatibility of the traditional Chinese medicine extract powder includes the following steps: S1. Sample Acquisition: Obtain samples of the Chinese herbal extract powder to be evaluated; S2. Powder Characterization: The powder characteristics of the traditional Chinese medicine extract powder samples were characterized to obtain a set of original values ​​for secondary indicators. The set of original values ​​for secondary indicators includes: median diameter. Particle size distribution width (Span), uniformity (Un), bulk density tap density Hausner ratio (HR), angle of repose (AR), and interparticle porosity The Cartesian index (CI), moisture content (MC), and hygroscopicity (H) were measured; and the true density was also determined. ; S3. Standardization and fingerprint construction: The original set of secondary indicators is converted into a set of radius values ​​from 0 to 10 according to a preset conversion relationship, and a physical fingerprint spectrum of the Chinese herbal extract powder sample is constructed based on the set of radius values. S4, SeDeM Index Quantification: Calculating Parameter Indexes Based on Radius Value Sets Parameter profile index With a good compressibility index And according to the parameter index Parameter profile index Good compressibility index Output the first direct voltage compatibility determination result; S5. Quantification of tablet compressibility: The traditional Chinese medicine extract powder sample is directly compressed into tablets, and the porosity of the tablets is measured. With the tensile strength of tablets And based on the Ryshkewitch–Duckworth equation, a system was established. With tablet porosity The fitting relationship is used to obtain the shapeability parameters. and And based on the tablet porosity Tablet tensile strength Output the second direct pressure compatibility determination result; S6. Comprehensive Output: The first direct pressure compatibility judgment result and the second direct pressure compatibility judgment result are used as a comprehensive basis to output the direct pressure compatibility evaluation result of the Chinese herbal extract powder sample.

2. The method for evaluating the direct compatibility of traditional Chinese medicine extract powder according to claim 1, characterized in that: The S1 mentioned above includes, S1.1 Drying into a dry extract: Drying the thick extract of traditional Chinese medicine into a dry extract; S1.2, Crushing and Sieving: The dry extract is crushed to obtain Chinese herbal extract powder; S1.3 Sealed storage: The sieved Chinese herbal extract powder is sealed and stored as a sample to be evaluated.

3. The method for evaluating the direct compatibility of traditional Chinese medicine extract powder according to claim 1, characterized in that: The S2 mentioned above includes, S2.1, Liquidity index measurement: Measurement of the angle of repose (AR); S2.2, Measurement and Derivation Calculation of Bulk Density: Measurement of Bulk Density With tap density and based on , Calculate the Karl index (CI), Hausner ratio (HR), and interparticle porosity. ; S2.3 True density determination: Determining the true density ; S2.4 Particle Size Distribution Measurement and Derivative Calculation: Measurement of particle size distribution parameters , , And calculate Span and uniformity Un based on particle size distribution parameters; S2.5, Moisture content determination: Determine the moisture content MC; S2.6, Hygroscopicity test: Measure the hygroscopicity H.

4. The method for evaluating the direct compression compatibility of traditional Chinese medicine extract powder according to claim 1, characterized in that: The S3 mentioned above includes, S3.1 Radius value conversion: Convert the radius value obtained in step S2 Particle size distribution width (Span), uniformity (Un), bulk density tap density Hausner ratio (HR), angle of repose (AR), and interparticle porosity The original values ​​of Karl index CI, moisture content MC, and hygroscopic rate H are converted into radius values ​​of 0 to 10 according to preset conversion relationships, forming a set of radius values; S3.2 Fingerprint mapping: Using the set of radius values ​​as the radii of each axis of the radar chart, construct the physical fingerprint of the Chinese herbal extract powder sample, and set the primary index corresponding to the physical fingerprint as uniformity, packing, flowability, compressibility, and stability.

5. The method for evaluating the direct compression compatibility of a traditional Chinese medicine extract powder according to claim 1, characterized in that, The S4 includes: S4.1, Comprehensive Index Calculation: Calculate the parameter index based on the radius value set from step S3. Parameter profile index With a good compressibility index ; S4.2, First Direct Voltage Adaptability Determination: Based on Parameter Index Parameter profile index Good compressibility index Output the first direct voltage compatibility determination result; In S4.1, let the total number of secondary indicators involved in the calculation be... The number of secondary indicators with a radius value of not less than 5 is NP. Then the parameter exponent , And when hour, .

6. The method for evaluating the direct compression compatibility of a traditional Chinese medicine extract powder according to claim 1, characterized in that, The S5 includes: S5.1 Direct compression: The traditional Chinese medicine extract powder sample is directly compressed into tablets without the addition of excipients; S5.2, Tablet Geometry and Mechanical Measurements: This includes measuring tablet hardness (F), tablet diameter (d), tablet thickness (t), and tablet mass. ; S5.3 Calculation of tablet quality parameters: Calculate the tensile strength of the tablet based on the measured tablet hardness F, tablet diameter d, and tablet thickness t. And based on tablet density and true density Calculate the solid fraction (SF) and tablet porosity. ; S5.4, Formability Fit and Second Judgment: Based on Tablet Tensile Strength With tablet porosity Establish the Ryshkewitch–Duckworth equation fitting relationship to obtain the shaping parameters. and Based on this, the second direct pressure adaptability judgment result is output.

7. The method for evaluating the direct compatibility of traditional Chinese medicine extract powder according to claim 1, characterized in that, S6 includes: outputting a physical fingerprint spectrum, a set of original values ​​for secondary indicators, a set of radius values, and parameter indices. Parameter profile index Good compressibility index Tablet tensile strength Solid fraction (SF) and tablet porosity , , The first direct pressure adaptability judgment result and the second direct pressure adaptability judgment result are used as a comprehensive basis to output the direct pressure adaptability evaluation result.

8. The method for evaluating the direct compression compatibility of a traditional Chinese medicine extract powder according to claim 3, characterized in that: In step S2.1, the fixed funnel method is used to allow the sample to naturally accumulate and form a cone. The height of the cone is measured as h, and the radius of the base is measured as r. The angle of repose AR is then calculated using the following formula: ; In S2.4, the particle size distribution parameters were measured. , , And calculate the particle size distribution width Span according to the following formula: Span = , ; In S2.2, the sample is filled into the graduated cylinder and leveled, the sample mass m is recorded, and the following calculations are performed. ; Vibrate until the volume stabilizes and read the volume v after vibration, then calculate. ; and calculate , , ; In S2.6, a sample with a thickness of 2 mm is placed in a weighing bottle and dried for 24 hours before being weighed to obtain the mass. The mass of the weighing bottle is ; The mass was then obtained by absorbing moisture and weighing. And calculate the moisture absorption rate according to the following formula. : .

9. The method for evaluating the direct compatibility of traditional Chinese medicine extract powder according to claim 4, characterized in that: The radius value in S3.1 is converted as follows: , ; ； ； 。 10. The method for evaluating the direct compatibility of traditional Chinese medicine extract powder according to claim 6, characterized in that: In S5.3, the tensile strength of the tablet ; Tablet volume Tablet density solid fraction Tablet porosity ; In S5.4, the Ryshkewitch–Duckworth equation is: ; and based on tablet porosity The tablet tensile strength is at 25±5%. This serves as the second threshold for judging direct pressure adaptability.

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