Stable chlorine dioxide effervescent tablet and preparation method thereof

Abstract

The invention provides a stable chlorine dioxide effervescent tablet and a preparation method thereof, and relates to the technical field of chlorine dioxide effervescent tablets, the stable chlorine dioxide effervescent tablet comprises the following components by weight: 50-100 parts of a chlorine dioxide releasing agent, 200-500 parts of an effervescing agent, 50-150 parts of a stabilizer, 20-80 parts of an adhesive, 10-50 parts of a wetting agent, and 50-150 parts of beta-cyclodextrin. According to the invention, through partitioned weighing and humidity adjustment of the releasing agent and the effervescing agent and by adopting a constant-temperature space and periodic humidity monitoring technology, accurate control and uniform adjustment of humidity are realized, and instability of raw materials in storage and reaction processes is reduced. A specific humidity control range and an electrostatic environment regulation measure are adopted in the mixing stage, so that the interference of electrostatic accumulation on the granulation process is effectively reduced, and the granulation uniformity and the material distribution stability are improved.

Description

Technical Field

[0001] The invention relates to the technical field of chlorine dioxide effervescent tablets, in particular to a stable chlorine dioxide effervescent tablet and a preparation method thereof. Background Art

[0002] The technical field of chlorine dioxide effervescent tablets involves the fields of chemistry and pharmaceutical engineering, focusing on the preparation and application of chlorine dioxide as a highly efficient oxidant and disinfectant. This field mainly focuses on the stable release technology of chlorine dioxide, the selection and optimization of carrier materials, the control mechanism of effervescent reactions, and its application in water treatment, food processing, medical and health care, and environmental disinfection.

[0003] In the preparation of existing chlorine dioxide effervescent tablets, the interference control of the electrostatic environment during the granulation process is insufficient, resulting in adhesion or uneven distribution of particles during molding, affecting the consistency and stability of the particles. The lack of accurate monitoring of the layered compaction parameters during the compaction stage, combined with the problem of insufficient strength, can easily cause tablet delamination or cracking, affecting the overall quality of the tablet. The residual stress inside the tablet is not effectively eliminated during the humidity balancing stage, and the tablet is prone to cracking or loss of strength during storage and use. Therefore, improvements are needed. Summary of the invention

[0004] The purpose of the present invention is to solve the shortcomings of the prior art and to propose a stable chlorine dioxide effervescent tablet and a preparation method thereof.

[0005] In order to achieve the above object, the present invention adopts the following technical scheme: a stable chlorine dioxide effervescent tablet, the stable chlorine dioxide effervescent tablet comprises the following components in parts by weight: 50-100 parts of chlorine dioxide releaser, 200-500 parts of effervescent agent, 50-150 parts of stabilizer, 20-80 parts of binder, 10-50 parts of wetting agent, 50-150 parts of beta-cyclodextrin, 20-60 parts of diatomaceous earth powder and 30-100 parts of hydroxyapatite.

[0006] Preferably, the chlorine dioxide releaser is sodium chlorate or sodium chloride, the effervescent agent is sodium carbonate, sodium bicarbonate, tartaric acid or citric acid, and the stabilizer is polyvinyl pyrrolidone, hydroxypropyl methylcellulose, mannitol or sorbitol.

[0007] Preferably, the binder is sodium carboxymethyl cellulose, starch, gelatin and gum arabic, and the wetting agent is polyethylene glycol, polysorbate 80, glycerol or propylene glycol.

[0008] The present invention provides a method for preparing a stable chlorine dioxide effervescent tablet, comprising the following steps: The chlorine dioxide releaser and effervescent agent are weighed and the humidity is adjusted in different areas, and the agents are placed in a constant temperature space and periodically tested and recorded by a humidity probe. The humidity values ​​are recorded at fixed time intervals and the dehumidification and humidification intensities are adjusted to generate raw material pretreatment products; The raw material pretreatment product, stabilizer and binder are mixed uniformly and the humidity is maintained in the range of 45 to 55 percent, and the layout of the ion wind jet head is optimized and the electrostatic potential data is recorded, the static charge accumulation is monitored and the static electricity removal intensity is adjusted to generate a granulated product; The granulated product, wetting agent and β-cyclodextrin are compacted in layers and the layer thickness and bonding strength are measured and the compaction uniformity is detected and the parameters of each layer are recorded, and different pressure sections are controlled and the alignment error of the upper and lower layers is confirmed and the feeding amount is corrected to generate a multilayer compact; The multilayer pressed body, diatomaceous earth powder and hydroxyapatite are stacked and the pulse frequency and pressure are set, and the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, and the change trend of the pressure curve is compared to generate a pulsed formed body; The pulse forming body is placed in a relative humidity range of 40 to 50 percent, humidity deviation is monitored at intervals, dehumidification and humidification parameters are adjusted, temperature fluctuations are recorded, compared with pre-set reference values, and data is summarized in sections, abnormal fluctuation rates are checked, and humidity balance sheets are generated; The moisture-balanced tablets are visually inspected, the tablet weight consistency and disintegration time are tested, the stability index is recorded, the pulse tabletting parameter records are compared, the tablet shape integrity and hardness are checked, the presence of cracks in the outer layer are recorded, the grouping and numbering and weighing records are performed, and the batch files are retrieved to generate the finished product.

[0009] Preferably, the steps of obtaining the pretreated raw material are: Weigh and adjust the humidity of chlorine dioxide releasers and effervescent agents in different areas, place them in a constant temperature space, and perform periodic detection and recording of humidity probes. Record humidity values ​​at fixed intervals and adjust dehumidification and humidification intensities. Divide the dosage and record batch parameters to generate basic weighing humidity data. Based on the weighed humidity basic data, compare the humidity probe readings in the constant temperature space and maintain the collection cycle, correct the humidity values ​​in the record table and control the dehumidification device and humidification system, perform partition verification and update the parameter list, and generate humidity adjustment records; Based on the humidity adjustment record, multi-point humidity probes are collected and the record table is integrated, the partitions are merged and the humidity interval values ​​are summarized, the dehumidification and humidification are compared and the final humidity range is confirmed to generate the raw material pretreatment product.

[0010] Preferably, the steps of obtaining the granulated product are: Based on the raw material pretreatment, stabilizer and adhesive are mixed and maintained in the humidity range of 45 to 55, the ion wind jet head is arranged and the electrostatic potential is recorded, the static charge is monitored and the static removal intensity is adjusted, the stirring operation is performed and the dispersion degree is collected, and the mixed humidity dispersion record is generated; Based on the mixed humidity dispersion record, the dispersion range is compared and the stabilizer ratio is adjusted, the electrostatic potential is measured at multiple points and the potential change is recorded, the ion wind jet head angle is corrected and the comparison results are collected to generate electrostatic monitoring data; Based on the electrostatic monitoring data, the electrostatic potential limit is confirmed and the stabilizer mixing uniformity is tested, the binder content is sampled and the humidity range is checked, the dispersed samples are reviewed and the key values ​​are recorded to generate the granulation product.

[0011] Preferably, the steps of obtaining the multilayer pressed body are: Based on the granulated product, wetting agent and β-cyclodextrin, compacting is performed in layers, compaction uniformity is detected and parameters of each layer are recorded, different pressure sections are controlled, alignment errors of upper and lower layers are confirmed and feeding amount is corrected, compaction equipment is operated at intervals and compaction density is collected to generate layered compaction records; Based on the layered pressing record, layer thickness comparison is performed and pressing uniformity data is checked, wetting agent content is sampled and values ​​are registered, β-cyclodextrin distribution is tested and a compaction structure list is formed, and pressing correction data is generated; Based on the pressing correction data, multi-stage pressure parameter comparison is performed and the feed rate is modified, the inter-layer ratio is reviewed and the layer thickness is confirmed, the pressing forming steady-state monitoring is performed and the strength of each layer is summarized to generate a multi-layer pressed body.

[0012] Preferably, the steps of obtaining the pulse forming body are: Based on the superposition of the multilayer pressed body, diatomaceous earth powder and hydroxyapatite, the pulse frequency and pressure are set, the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, the pulse device is operated at intervals and the pressure peak is collected to generate a pulse pressing record; Based on the pulse suppression record, pulse frequency comparison is performed and impact interval is corrected, multi-point measurement of temperature sensor is performed and instantaneous readings are compared, pressure curve segmentation check is performed and pulse parameters are updated to generate temperature and pressure monitoring data; Based on the temperature and pressure monitoring data, the pressure peak value is compared with the instantaneous reading and the pulse frequency is corrected, the pulse duration is confirmed and the tableting stability information is recorded, the diatomaceous earth powder and hydroxyapatite stacking condition is reviewed, and a pulse molded body is generated.

[0013] Preferably, the steps of obtaining the humidity balancing sheet are: The pulse forming body is placed in a relative humidity range of 40 to 50, the humidity deviation is monitored at intervals, the dehumidification and humidification parameters are adjusted, the temperature fluctuation is recorded and compared with the reference value, the sensor is repeatedly sampled and the data list is corrected to generate the humidity monitoring record; Based on the humidity monitoring records, humidity deviation comparison is performed and the static time is updated, dehumidification device and humidification system switching operation is performed and parameter range is corrected, temperature fluctuation data is summarized multiple times and abnormal values ​​are identified to generate static summary data; Based on the static summary data, perform segmented analysis of humidity and temperature curves and supplement monitoring records, recheck deviation values ​​and troubleshoot abnormal fluctuations, confirm the switching of dehumidification and humidification devices and register the correction results to generate a humidity balance sheet.

[0014] Preferably, the steps of obtaining the prepared product are: Conduct appearance screening of moisture-balanced tablets and test tablet weight consistency and disintegration time, record stability indicators and compare pulse tableting parameter records, conduct tablet shape integrity and hardness tests and observe the outer layer crack conditions to generate appearance inspection data; Based on the appearance inspection data, tablet weight consistency comparison is performed and disintegration time information is checked, stability indicators are recorded multiple times and compared with pulse tableting parameters, outer layer crack conditions are re-screened and inspection results are summarized to generate finished product inspection records; Based on the finished product inspection record, the sheet hardness and outer layer crack data are compared and the screening results are confirmed, grouping and numbering and weighing operations are performed and batch files are integrated, and the record signing steps are performed and archived to obtain the prepared finished product.

[0015] 1. Compared with the prior art, the present invention can improve the embedding stability of chlorine dioxide and form inclusion compounds by adding β-cyclodextrin, achieve sustained release effect and reduce volatilization loss; at the same time, the diatomaceous earth powder used in the formula can further stabilize chlorine dioxide with its excellent adsorption and porous structure, improve tablet disintegration performance and control moisture to improve storage stability; and the addition of hydroxyapatite brings good biocompatibility and safety, which can be used as a carrier material to provide a sustained release platform and improve the mechanical strength of the tablet. These improvements have comprehensively improved the product in terms of stability, release control, safety and physical properties.

[0016] 2. Compared with the prior art, the present invention achieves precise humidity control and uniform adjustment by zoning weighing and humidity adjustment of the release agent and effervescent agent, and adopts constant temperature space and periodic humidity monitoring technology, thereby reducing the instability of the raw materials during storage and reaction. The mixing stage adopts a specific humidity control range and electrostatic environment adjustment measures to effectively reduce the interference of static electricity accumulation on the granulation process, improve the uniformity of granulation and the stability of material distribution. The compaction process is based on layered measurement and bonding strength detection, combined with real-time feeding adjustment and optimization of different pressure sections, which enhances the interlayer bonding and structural integrity of the tablet body and improves the overall molding quality. The molding stage uses real-time monitoring and adjustment of temperature and pressure to achieve dynamic stability management during the molding process and reduce the accumulation of stress in the tablet structure. Humidity balance treatment eliminates the hidden dangers of microcracks in the tablet body through humidity control and stress release, and improves the physical strength and consistency of the product's disintegration time. The final detection link integrates multi-dimensional parameters such as tablet weight, disintegration time, and stability, realizes a comprehensive evaluation of the appearance integrity and quality consistency of the tablet body, and promotes the improvement of product performance and quality.

[0017] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0019] Figure 1 The present invention provides a preparation process diagram of a method for preparing a stable chlorine dioxide effervescent tablet. DETAILED DESCRIPTION

[0020] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0021] Embodiment 1, a stable chlorine dioxide effervescent tablet, the stable chlorine dioxide effervescent tablet comprises the following components in parts by weight: 100 parts of chlorine dioxide releaser, 200 parts of effervescent agent, 150 parts of stabilizer, 80 parts of binder, 10 parts of wetting agent, 150 parts of beta-cyclodextrin, 20 parts of diatomaceous earth powder and 100 parts of hydroxyapatite.

[0022] In this embodiment, the chlorine dioxide releaser is sodium chlorate, the effervescent agent is sodium carbonate, and the stabilizer is polyvinyl pyrrolidone.

[0023] In this embodiment, the binder is sodium carboxymethyl cellulose and the wetting agent is polyethylene glycol.

[0024] This embodiment provides a method for preparing a stable chlorine dioxide effervescent tablet, comprising the following steps: The chlorine dioxide releaser and effervescent agent are weighed and the humidity is adjusted in different areas, and the agents are placed in a constant temperature space and periodically tested and recorded by a humidity probe. The humidity values ​​are recorded at fixed time intervals and the dehumidification and humidification intensities are adjusted to generate raw material pretreatment products; The raw material pretreatment, stabilizer and binder are mixed uniformly and the humidity is maintained in the range of 45 to 55 percent, and the layout of the ion wind jet head is optimized and the electrostatic potential data is recorded, the static charge accumulation is monitored and the static electricity removal intensity is adjusted to generate a granulated product; The granulated product, wetting agent and β-cyclodextrin are compacted in layers and the layer thickness and bonding strength are measured and the compaction uniformity is detected and the parameters of each layer are recorded, and different pressure sections are controlled and the alignment error of the upper and lower layers is confirmed and the feeding amount is corrected to generate a multilayer compact; The multilayer pressed body, diatomaceous earth powder and hydroxyapatite are stacked and the pulse frequency and pressure are set, and the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, and the pressure curve change trend is compared to generate a pulsed formed body; The pulse forming body is placed in a relative humidity range of 40 to 50 percent, humidity deviation is monitored at intervals, dehumidification and humidification parameters are adjusted, temperature fluctuations are recorded, compared with pre-set reference values, and data is summarized in sections, abnormal fluctuation rates are checked, and humidity balance sheets are generated; Conduct appearance inspection on moisture-balanced tablets, test tablet weight consistency and disintegration time, record stability indicators, compare pulse tablet compression parameter records, check tablet shape integrity and hardness, record whether there are cracks in the outer layer, group and number tablets, record weighing, and retrieve batch files to generate finished products.

[0025] In this embodiment, the steps for obtaining the raw material pretreatment product are: Weigh and adjust the humidity of chlorine dioxide releasers and effervescent agents in different areas, place them in a constant temperature space, and perform periodic detection and recording of humidity probes. Record humidity values ​​at fixed intervals and adjust dehumidification and humidification intensities. Divide the dosage and record batch parameters to generate basic weighing humidity data. Based on the basic data of weighing humidity, compare the humidity probe readings in the constant temperature space and maintain the collection cycle, correct the humidity values ​​in the record table and control the dehumidification device and humidification system, check the partitions and update the parameter list, and generate humidity adjustment records; Based on the humidity adjustment records, multi-point humidity probes are collected and the record table is integrated, the partitions are merged and the humidity interval values ​​are summarized, the dehumidification and humidification are compared and the final humidity range is confirmed to generate the raw material pretreatment.

[0026] Specifically, the chlorine dioxide releaser and effervescent agent are weighed and the humidity is adjusted in different areas. During the specific implementation, a basic humidity range, such as 30% to 70%, is first set as an initial reference and corrected according to experience and historical records. If the actual humidity measured is lower than 30%, a humidifier is used to adjust it until it returns to the set range. If it is higher than 70%, a dehumidifier is used to repeatedly perform dehumidification operations until it meets the requirements. During this period, the humidity obtained from each measurement is compared with the pre-established effective range between 0% and 100% and recorded, and the test results are associated with the material information of the corresponding area to determine the matching degree of the amount of chlorine dioxide releaser and effervescent agent in the area, and then the actual weighing data is compared with the established formula parameters according to the ratio indication to determine whether it is necessary A secondary weighing calibration is required. In this process, the dosage is divided according to the previously obtained chlorine dioxide releaser partition allocation results and the effervescent agent partition allocation results, and they are marked correspondingly with the batch parameters to facilitate subsequent inquiries and repeated tests. Then, interval collection is carried out for possible humidity fluctuations in the constant temperature space, and a fixed time interval is used, such as reading the probe data every five minutes and recording it once. If a certain collection result exceeds the specified threshold, such as higher than 75% or lower than 25%, the humidification or dehumidification strategy is adjusted again through the empirical correction method. The threshold of the empirical correction method is set by the operator based on previous test data and can be continuously updated according to new data. When all data meet the requirements of partition weighing and humidity adjustment, the basic weighing humidity data is generated.

[0027] Based on the basic data of weighing humidity obtained previously, during the execution process, each humidity collection moment is first retrieved in chronological order, and the humidity probe reading in the constant temperature space is compared with the value recorded at the same time. If the difference between the two is greater than 3%, which is the interval obtained by empirical statistics, it is necessary to further check whether the probe has a reading offset. After confirming that the probe reading itself is correct, the difference is used as a mark value that needs to be corrected and the working frequency of the dehumidification or humidification system is adjusted. For example, when multiple tests find that the humidity exceeds 70%, the working cycle of the dehumidification device can be shortened to once every two minutes, and repeated records and continuous observations are made until the humidity returns to between 45% and 55%. Then, according to the previously obtained partition verification requirements, the parameter list corresponding to each partition is compared with the new round of humidity test results. If the actual humidity in the partition differs from the target humidity given in the parameter list by more than 5%, compensation is made based on the humidity correction range statistically calculated in previous tests. This correction range is the most common correction range obtained by analyzing historical data of different batches. After the final humidity data of each partition is updated, a humidity adjustment record is generated.

[0028] Based on the humidity adjustment record obtained above, in the specific implementation, multi-point humidity probe collection is first performed one by one according to the timestamp and partition information contained in the record, and the real-time humidity value of each collection point is viewed in parallel with the previous correction result. If any record deviates from the previously corrected humidity value by more than 2%, the humidification or dehumidification equipment needs to be restarted and dynamically adjusted according to the reference threshold set by the operator's experience. For example, when the humidity in partition A is lower than 30%, the humidification program will be started immediately and the humidification intensity will be gradually increased in steps of 1% until the detection value gradually approaches between 45% and 55%. At a fixed frequency, such as every three minutes, the probe readings are cross-compared with historical records to evaluate short-term stability. After completing the sampling of all partitions, the data of all time periods are horizontally summarized and the average and fluctuation range of the humidity in each partition are calculated. If the fluctuation range of some partitions still exceeds the pre-defined normal limit of 3% to 5%, further dehumidification or humidification comparison can be performed before the partitions are merged. Finally, when all the partition data are finally merged, the humidity value is controlled within 40% to 60% and the corresponding interval statistical information is established. After confirming the final humidity range of all partitions, the raw material pretreatment is generated.

[0029] In this embodiment, the steps for obtaining the granulated product are: Based on the raw material pretreatment, stabilizer and adhesive are mixed and maintained in the humidity range of 45 to 55, the ion wind jet head is arranged and the electrostatic potential is recorded, the static charge is monitored and the static removal intensity is adjusted, the stirring operation is performed and the dispersion degree is collected, and the mixed humidity dispersion record is generated; Based on the mixed humidity dispersion record, the dispersion range is compared and the stabilizer ratio is adjusted. The electrostatic potential is measured at multiple points and the potential change is recorded. The ion wind jet head angle is corrected and the comparison results are collected to generate electrostatic monitoring data. Based on the static monitoring data, the static potential limit is confirmed and the stabilizer mixing uniformity is tested. The binder content is sampled and the humidity range is checked. The dispersed samples are reviewed and key values ​​are recorded to generate granulation products.

[0030] Specifically, based on the raw material pretreatment obtained above and the stabilizer and adhesive prepared in advance, the overall humidity is controlled between 45% and 55%. In the specific operation, the stabilizer and the raw material pretreatment are first mixed in a mass ratio of 2:1 and the adhesive is added to observe the humidity change. If the humidity value is detected to deviate from the 45% to 55% range, the humidification equipment or the static electricity removal device is used for fine adjustment. Then, the layout is carried out according to the predetermined number and position placement requirements of the ion wind injection heads, and the static electricity potential generated by the injection heads is collected at a fixed point. If the potential exceeds the value determined by previous test statistics, The ±20V range obtained means that the static electricity accumulation is high. At this time, it is necessary to increase the ion wind spray intensity or extend the spray time. When the static electricity condition tends to stabilize, start the stirring device and stir evenly at a speed of 200rpm to 300rpm. During the process, the dispersion of the mixture is measured every 10 minutes and compared with the pre-established qualified interval, such as the dispersion coefficient interval of 0.8 to 1.2. If it exceeds this interval, the adhesive addition amount or stabilizer ratio needs to be re-evaluated. When all detection points remain within the dispersion coefficient interval, a mixed humidity dispersion record is generated.

[0031] Based on the mixed humidity dispersion record obtained above, in the dispersion range comparison stage, it is necessary to first extract the dispersion data of multiple time points from the record and judge according to the qualified range of 0.8 to 1.2. If the dispersion is detected to be higher than 1.2 at some time points, it means that the current stabilizer ratio may need to be adjusted down. If the dispersion is lower than 0.8, the stabilizer dosage needs to be adjusted up. The increase or decrease range can be determined by the average value of multiple historical adjustments. For example, the adjustment range is initially set to 0.5% each time. After completing such adjustments, the electrostatic potential is measured at multiple points. During the measurement, the data can be collected at segmented time intervals under the same stirring rate and humidity environment, and the obtained potential value is compared with the normal range of ±20V obtained by statistics before. If it is found that the potential exceeds ±25V in a certain period of time, which is a critical value established based on accumulated experience, it is necessary to fine-tune the intensity or duration of the ion wind jet again, and then calibrate the angle of the jet and observe the potential change after adjustment in real time. If the potential is restored to within ±20V, it means that the intensity and angle remain relatively stable under the current humidity dispersion conditions. Finally, the electrostatic change results of all measurement periods are summarized to generate electrostatic monitoring data.

[0032] Based on the electrostatic monitoring data obtained above, the limit of the electrostatic potential is first determined and compared with the preset interval of ±20V, which is the average range obtained after analyzing the historical potential distribution of multiple batches in the past. If it is found that the current electrostatic potential exceeds ±25V at any time, the warning value obtained by statistical analysis, it is necessary to adjust the ion wind injection intensity or extend the injection time again. When the electrostatic potential remains within the preset interval, the mixing uniformity of the stabilizer is tested. The test can be completed by sequentially sampling the mixture samples at several positions and comparing the proportions of their main components. If the test results show that the stabilizer content error at a certain position exceeds 0.5%, the deviation threshold verified by multiple batches, the stirring time and the order of adhesive addition are continued to be optimized. Subsequently, the adhesive content is randomly sampled while ensuring that the humidity is maintained between 45% and 55%. If the sampling results are all within the range of ±0.3%, which is determined based on previous experience, the dispersed samples are reviewed again and the key values ​​of dispersion and potential are recorded. After completing all the above operations, a granulation product is generated.

[0033] In this embodiment, the steps for obtaining the multilayer pressed body are: Based on the granulation product, wetting agent and β-cyclodextrin, the compaction uniformity is tested and the parameters of each layer are recorded. Different pressure sections are controlled and the alignment error of the upper and lower layers is confirmed and the feeding amount is corrected. The compaction equipment is operated at intervals and the compaction density is collected to generate a layered compaction record. Based on the layered pressing records, layer thickness comparison and pressing uniformity data are checked, wetting agent content is sampled and the value is registered, β-cyclodextrin distribution is tested and a compaction structure list is formed, and pressing correction data is generated; Based on the pressing correction data, multi-stage pressure parameter comparison is carried out and the feeding rate is modified, the inter-layer ratio is reviewed and the layer thickness is confirmed, the pressing forming steady-state monitoring is carried out and the strength of each layer is summarized to generate a multi-layer pressed body.

[0034] Specifically, based on the granulation product, wetting agent and β-cyclodextrin obtained above, layered compaction is performed. During the execution process, the mass ratio of the granulation product and the addition criteria of the wetting agent are first confirmed according to the formula instructions extracted in advance. The preliminarily prepared layer mixture is laid on the working area of ​​the compaction equipment at a fixed rate and pressed in stages using the pressure range set by experience. For example, the pressure is divided into three intervals of 0MPa to 1MPa, 1MPa to 2MPa and 2MPa to 3MPa. The compression uniformity value after each compression is compared with the deviation range of 0% to 5%. The range is compared to determine whether correction is needed, and then the alignment error of the upper and lower layers is checked and its changing trend between 0mm and 2mm is recorded. If the alignment deviation is found to exceed 2mm, which is the limit value obtained according to previous test experience, the feed amount is corrected in time, and the equipment is paused every few minutes to collect the compaction density. If the density value is between 90% and 100%, it is considered to meet the preset standard. The standard range of 90% to 100% is the average range determined by comparing multiple batches. After completing multiple cycles of compaction and testing, a layered pressing record is generated.

[0035] Based on the layered pressing records obtained previously, during the execution process, the average thickness data and pressing uniformity values ​​of each layer are first extracted from them, and then these data are matched one by one with the wetting agent content indicators sorted out earlier. If the wetting agent content is between 0.5% and 1.0%, it is considered normal. If it exceeds or is lower than this range, the pressing parameters of the layer segment are reviewed and the abnormal situation is recorded. At the same time, the β-cyclodextrin distribution information is compared with the data of each layer. If it is found that the distribution result of a certain layer is significantly different from the previous layered pressing record, for example, the deviation exceeds 2%, the timing pressing parameters of the layer during the compaction process are further tracked. The 2% threshold is determined based on the previous experience summary and actual verification, and the layer thickness comparison is recorded one by one. After completing the above operations, the pressing uniformity of each layer and the distribution of β-cyclodextrin are sorted into a compaction structure list, and the pressing correction data is obtained comprehensively.

[0036] Based on the pressing correction data obtained above, in the specific implementation, the pressure adjustment range of the equipment is first divided into several gears according to the configuration information of the multiple pressure sections, such as 0MPa to 1MPa, 1MPa to 2MPa and 2MPa to 3MPa, and the corresponding feed rate correction value of each gear is extracted and compared with the feeding state during actual production. If it is found that the feed rate deviates from the preset value by more than 5%, and the 5% value is calculated based on multiple production practices and the statistical results obtained above, it should be corrected immediately and its impact on the multi-layer pressing molding effect should be re-observed. After the pressure gear is corrected, the inter-layer ratio is reviewed again, mainly by comparing the mass ratio records of each layer and confirming that the layer thickness is within the range of 3mm to 5mm. If the layer thickness exceeds 5mm or is lower than 3mm, the feed amount is lowered or increased again and it is observed whether it meets the correction requirements. After ensuring that the pressure gear and thickness of each layer meet the requirements of the current equipment and formula, the pressing molding is monitored at intervals in a steady state and the final strength value of each layer is statistically calculated. Finally, all measurement results are summarized to generate a multi-layer pressed body.

[0037] In this embodiment, the steps for obtaining the pulse forming body are: Based on the superposition of multi-layer pressed bodies, diatomaceous earth powder and hydroxyapatite, the pulse frequency and pressure are set, and the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, the pulse device is operated at intervals and the pressure peak is collected to generate a pulse pressing record; Based on the pulse suppression record, the pulse frequency is compared and the impact interval is corrected, the temperature sensor is measured at multiple points and the instantaneous readings are compared, the pressure curve is checked in sections and the pulse parameters are updated to generate temperature and pressure monitoring data; Based on the temperature and pressure monitoring data, the pressure peak value is compared with the instantaneous reading and the pulse frequency is corrected. The pulse duration is confirmed and the tableting stability information is recorded. The stacking of diatomaceous earth powder and hydroxyapatite is reviewed to generate a pulsed molded body.

[0038] Specifically, based on the multilayer pressed body obtained previously and the diatomaceous earth powder and hydroxyapatite ratio information obtained by disassembly and extraction, the multilayer pressed body is first spread flat in the working area and diatomaceous earth powder is evenly sprinkled on its surface in the range of 0.1g to 0.3g. At the same time, check whether the originally set pulse frequency and pressure setting values ​​are in the appropriate working range, such as the pulse frequency is 10Hz to 20Hz, and the pulse pressure is 2MPa to 3MPa. If the actual measured frequency or pressure deviates from these ranges, corrections should be made immediately. Then, temperature sensors are arranged on the equipment to record the instantaneous readings at each pulse at fixed time intervals and compare them with the reference range of 0℃ to 90℃. If the instantaneous temperature is found to exceed 90℃, the equipment is paused to check whether it is caused by sensor failure or abnormal superposition. After confirmation, the pulse operation is continued and the pressure peak is collected during the interval operation of the equipment. The peak is compared one by one with the previously specified 2MPa to 3MPa range. Finally, all records that meet the pulse conditions are summarized to generate pulse compression records.

[0039] Based on the pulse suppression record obtained previously, during the execution process, the pulse frequency is first read in chronological order and checked one by one with the impact interval standard obtained in advance. If the pulse frequency differs from the standard by more than 2Hz, the 2Hz value is the stable range obtained after combining multiple pulse tests, and it should be corrected immediately. Then, the instantaneous temperature is measured one by one at the multi-point layout positions of the matching temperature sensors, and these temperature values ​​are compared with the effective range between 0℃ and 90℃. If any reading is above 90℃, the pulse parameters are reduced accordingly. At the same time, the pressure curves of different pulse time periods are divided into several intervals and the maximum and minimum peak values ​​are compared in each interval. If the peak value exceeds the interval of 2MPa to 3MPa, it is classified as an abnormal segment and the pulse parameters are updated. After completing all pulse detections, the temperature and pressure monitoring data are obtained.

[0040] Based on the temperature and pressure monitoring data obtained previously, the pressure peak and the instantaneous temperature reading are first divided into sections and checked for their corresponding relationship during execution. If it is found that a certain section of the pressure peak exceeds 3MPa, a threshold value set by the equipment performance and multiple pulse tests, the pulse frequency is further adjusted to avoid equipment failure under excessively high pressure. The adjustment can be gradually corrected downward by reducing 1Hz each time. When the pulse frequency and the pressure peak return to their respective safety ranges, the pulse duration is confirmed and compared with the duration setting value obtained from the previous disassembly, such as the interval of 1s to 3s. If the actual pulse duration deviates from this interval, the duration is shortened or extended again through empirical judgment. At the same time, the stacking contact status of the diatomaceous earth powder and the hydroxyapatite is observed and reviewed section by section. Finally, all completed test information is summarized to generate a pulsed body.

[0041] In this embodiment, the steps for obtaining the humidity balance sheet are: The pulse forming body is placed in a relative humidity range of 40 to 50, the humidity deviation is monitored at intervals, the dehumidification and humidification parameters are adjusted, the temperature fluctuation is recorded and compared with the reference value, the sensor is repeatedly sampled and the data list is corrected to generate the humidity monitoring record; Based on the humidity monitoring records, humidity deviation comparison is performed and the static time is updated. The dehumidification device and humidification system are switched and the parameter range is corrected. The temperature fluctuation data is summarized multiple times and abnormal values ​​are identified to generate static summary data. Based on the static summary data, perform segmented analysis of the humidity and temperature curves and supplement monitoring records, re-check the deviation values ​​and check for abnormal fluctuations, confirm the switching of the dehumidification and humidification devices and register the correction results to generate a humidity balance sheet.

[0042] Specifically, the pulse forming body is left to stand at a relative humidity range of 40% to 50%. During the specific execution, the monitoring interval is first determined based on the material information of the forming body extracted by disassembly and the humidity monitoring reference value, and a humidity range of 40% to 50% is preset. If the actual detection value is lower than 40%, the humidification device is turned on and the humidity is gradually increased in steps of 1% or 2%. The step size is determined based on the humidity stability study and multi-batch statistical results obtained previously. If the actual detection value is higher than 50%, the dehumidification device is started and the dehumidification operation is performed in the same step size. During this process, a temperature sensor is used to record temperature fluctuations and compare them with an effective control range of 0°C to 90°C. If the temperature deviates from 90°C or more, the humidification or dehumidification process is paused to check the sensor and equipment. Status, continue to record at intervals after confirming that the equipment and data are normal, and compare the current humidity value with the initial interval of 40% to 50% each time you re-record. If the error exceeds the critical value of 5%, the humidification or dehumidification intensity is corrected according to the average deviation of previous monitoring. The 5% critical value is calculated based on the actual environment and historical data. At the same time, repeatedly sample the humidity readings of each sensor and include the difference between any two readings in the error distribution analysis. If the difference exceeds 2%, the limit value obtained by the deviation statistics of the same batch of products, calibrate the sensor again or replace the spare equipment. After multiple rounds of measurement and adjustment, record the temperature fluctuation and compare it with the reference value set previously. Finally, integrate all the collected humidity and temperature information to generate a humidity monitoring record.

[0043] Based on the humidity monitoring records obtained above, the difference is compared with the timestamp in the record and the humidity value during the specific execution. If the humidity deviation in a certain period is higher than 5% (a range determined by actual tests and historical experience), the static time is extended and the dehumidification device or humidification system is started again to gradually return the humidity to between 40% and 50%. During this process, the frequency of device switching operations is checked and a maximum switching number is set according to previous monitoring data, for example, no more than 5 times per hour. If frequent switching leads to continuous fluctuations, the intensity of humidification or dehumidification should be reduced, and each corrected temperature fluctuation is included in the summary and a temperature range of 0°C to 90°C is used. The temperature is taken as the basic control. If it is detected that the reading exceeds 90℃ in certain periods, check whether the humidification equipment or dehumidification device is working abnormally. After confirmation, repeat the test several times to eliminate the abnormal instantaneous data. At the same time, when identifying abnormal values, first trace back to the corresponding multiple measuring points in steps of 1℃. If three consecutive samplings exceed 90℃, it is regarded as high temperature and the steam temperature in the humidification process or the equipment heat in the dehumidification process is reduced. After all the temperature fluctuation data are merged, it is determined whether it is stable between 0℃ and 90℃. If outliers appear, recheck the execution link of the humidification or dehumidification action. Finally, all adjustments and data are merged to generate static summary data.

[0044] Based on the static summary data obtained above, the humidity and temperature are first analyzed in the time dimension in a segmented manner during the specific execution. For example, the entire static process is divided into several periods and the maximum and minimum humidity values ​​and the corresponding temperature are recorded in each period. If the lowest humidity value in a certain period is lower than 40%, the humidification amount is gradually increased using an empirical judgment method. The basis of this empirical judgment method is the historical comparison of the humidification effect and the humidity recovery rate of each period obtained above. If the highest humidity exceeds 50%, the dehumidification intensity is enhanced in the same way. Then, at the end of each period, the measured value is re-measured and compared with the target range of 40% to 50%. If it still deviates by more than 3%, the working status of the equipment in the period is re-evaluated, and the deviation that still occurs after verification is recorded in the abnormal list, and the temperature fluctuation in the abnormal period is marked in detail. Then, the dehumidification and humidification devices are switched and confirmed, and the start time and end time of each switching operation and the switching parameters are recorded so that they can be quickly traced back when larger fluctuations occur in the subsequent stage. Finally, the monitoring data is supplemented after the segmented inspection of the entire static process, and the results of confirming no abnormal fluctuations in all segments are merged to generate a humidity balance sheet.

[0045] In this embodiment, the steps for obtaining the finished product are: Conduct appearance screening of moisture-balanced tablets and test tablet weight consistency and disintegration time, record stability indicators and compare pulse tableting parameter records, conduct tablet shape integrity and hardness tests and observe the outer layer crack conditions to generate appearance inspection data; Based on the appearance inspection data, tablet weight consistency comparison and disintegration time information are checked, stability indicators are recorded multiple times and compared with pulse tableting parameters, outer layer cracks are re-screened and inspection results are summarized to generate finished product inspection records; Based on the finished product inspection records, the sheet hardness and outer crack data are compared and the screening results are confirmed. Grouping and numbering and weighing operations are performed and batch files are integrated. The record signing steps are performed and archived to obtain the finished product.

[0046] Specifically, the moisture-balanced tablets obtained above are screened for appearance and the tablet weight consistency and disintegration time are tested. During the specific implementation, each tablet is weighed first and the measured weight is compared with a known reference value, such as a range of 1g to 2g. If a tablet weighs less than 1g or more than 2g, it is included in the abnormal statistics and the specific number of the batch is recorded. At the same time, the disintegration time interval set by the operator, such as 30 seconds to 90 seconds, is used to test the decomposition speed of each tablet. If the disintegration time of a tablet exceeds 90 seconds, it is also registered and compared with the pulse compression parameters obtained by the previous disassembly, and the pressure recorded in the parameters is matched with the time period to confirm whether there is abnormal compression. If it is found that multiple tablets compressed in the same period of time in this batch exceed the specified disintegration time, it may indicate that there is a deviation in the pressure setting or temperature control during this period. At this time, the instantaneous data of the pulse tableting parameters can be checked again. After confirming that there is no obvious fluctuation in the parameters, you can further check whether there is an impact of temperature and humidity fluctuations. If the temperature in the corresponding record is indeed between 0℃ and 90℃ but the disintegration time of the continuous tablets is long, enter a more in-depth screening process, then check the tablet integrity and hardness, and observe whether there are cracks in the outer layer of each tablet, compare the observation results with the corresponding pulse tableting parameters, and finally summarize all the results to generate appearance inspection data.

[0047] Based on the appearance inspection data obtained previously, the tablet weight consistency is compared and the difference between any two tablets is checked during specific execution. If the difference exceeds 0.1g, the upper limit of the deviation obtained from batch production statistics, it is judged that the weight difference is large and the batch is marked as requiring further analysis. At the same time, the disintegration time information is compared with the set standard of 30 seconds to 90 seconds. If it is found that multiple consecutive tablets are above 90 seconds, the pulse tableting parameters of this period are re-called for cross-reference. After confirming that the parameters are correct, the stability index data extracted from the previous disassembly are reviewed and recorded multiple times. If there is no abnormal fluctuation in stability within the same period, it is preliminarily judged that it is caused by uneven distribution of individual tablet raw materials or slight temperature changes. Subsequently, the outer layer crack screening results are also included in the comprehensive statistics. Once it is found that the outer layer crack occurrence rate exceeds 5%, the limit inferred from the benchmark data of similar products and previous test results, it will be recorded first. Finally, all inspection results are combined in sequence to generate finished product inspection records.

[0048] Based on the finished product inspection records obtained previously, in the specific implementation, the sheet hardness data in the record is first compared with the detection results of the outer cracks one by one. If the hardness is lower than a certain critical value, such as 30N, and the crack detection rate is higher than 5% in the same period, and the value of 30N is based on the average measurement results of multiple previous tests, then further check whether there is a fluctuation in the ratio of grouped batches of raw materials, and reconfirm the weighing records of this batch of raw materials. If the abnormality cannot be eliminated after confirmation, the operator is enabled to manually check the fault and give a conclusion. After confirming that all sheet hardness and crack distribution meet the previous pre-judgment criteria, the finished product is then weighed according to the group number and indexed accordingly with the batch file. After that, the arrangement information of each batch is summarized and the relevant signatures are registered. Finally, all processed data are summarized to obtain the prepared finished product.

[0049] Example 2, which is different from Example 1, is as follows: 80 parts of chlorine dioxide releaser, 300 parts of effervescent agent, 150 parts of stabilizer, 80 parts of binder, 10 parts of wetting agent, 70 parts of β-cyclodextrin, 30 parts of diatomaceous earth powder, and 100 parts of hydroxyapatite.

Claims

1. A stable chlorine dioxide effervescent tablet, characterized in that: The stable chlorine dioxide effervescent tablet comprises the following components in parts by weight: 50-100 parts of chlorine dioxide releaser, 200-500 parts of effervescent agent, 50-150 parts of stabilizer, 20-80 parts of binder, 10-50 parts of wetting agent, 50-150 parts of beta-cyclodextrin, 20-60 parts of diatomaceous earth powder and 30-100 parts of hydroxyapatite.

2. The stable chlorine dioxide effervescent tablet according to claim 1, characterized in that: The chlorine dioxide releaser is sodium chlorate or sodium chloride, the effervescent agent is sodium carbonate, sodium bicarbonate, tartaric acid or citric acid, and the stabilizer is polyvinyl pyrrolidone, hydroxypropyl methylcellulose, mannitol or sorbitol.

3. The stable chlorine dioxide effervescent tablet according to claim 1, characterized in that: The binder is sodium carboxymethyl cellulose, starch, gelatin and gum arabic, and the wetting agent is polyethylene glycol, polysorbate 80, glycerol or propylene glycol.

4. A method for preparing a stable chlorine dioxide effervescent tablet, characterized in that: The following steps are involved: The chlorine dioxide releaser and effervescent agent are weighed and the humidity is adjusted in different areas, and the agents are placed in a constant temperature space and periodically tested and recorded by a humidity probe. The humidity values ​​are recorded at fixed time intervals and the dehumidification and humidification intensities are adjusted to generate raw material pretreatment products; The raw material pretreatment product, stabilizer and binder are mixed uniformly and the humidity is maintained in the range of 45 to 55 percent, and the layout of the ion wind jet head is optimized and the electrostatic potential data is recorded, the static charge accumulation is monitored and the static electricity removal intensity is adjusted to generate a granulated product; The granulated product, wetting agent and β-cyclodextrin are compacted in layers and the layer thickness and bonding strength are measured and the compaction uniformity is detected and the parameters of each layer are recorded, and different pressure sections are controlled and the alignment error of the upper and lower layers is confirmed and the feeding amount is corrected to generate a multilayer compact; The multilayer pressed body, diatomaceous earth powder and hydroxyapatite are stacked and the pulse frequency and pressure are set, and the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, and the change trend of the pressure curve is compared to generate a pulsed formed body; The pulse forming body is placed in a relative humidity range of 40 to 50 percent, humidity deviation is monitored at intervals, dehumidification and humidification parameters are adjusted, temperature fluctuations are recorded, compared with pre-set reference values, and data is summarized in sections, abnormal fluctuation rates are checked, and humidity balance sheets are generated; The moisture-balanced tablets are visually inspected, the tablet weight consistency and disintegration time are tested, the stability index is recorded, the pulse tabletting parameter records are compared, the tablet shape integrity and hardness are checked, the presence of cracks in the outer layer are recorded, the grouping and numbering and weighing records are performed, and the batch files are retrieved to generate the finished product.

5. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps for obtaining the raw material pretreatment product are: Weigh and adjust the humidity of chlorine dioxide releasers and effervescent agents in different areas, place them in a constant temperature space, and perform periodic detection and recording of humidity probes. Record humidity values ​​at fixed intervals and adjust dehumidification and humidification intensities. Divide the dosage and record batch parameters to generate basic weighing humidity data. Based on the weighed humidity basic data, compare the humidity probe readings in the constant temperature space and maintain the collection cycle, correct the humidity values ​​in the record table and control the dehumidification device and humidification system, perform partition verification and update the parameter list, and generate humidity adjustment records; Based on the humidity adjustment record, multi-point humidity probes are collected and the record table is integrated, the partitions are merged and the humidity interval values ​​are summarized, the dehumidification and humidification are compared and the final humidity range is confirmed to generate the raw material pretreatment product.

6. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps of obtaining the granulated product are: Based on the raw material pretreatment, stabilizer and adhesive are mixed and maintained in the humidity range of 45 to 55, the ion wind jet head is arranged and the electrostatic potential is recorded, the static charge is monitored and the static removal intensity is adjusted, the stirring operation is performed and the dispersion degree is collected, and the mixed humidity dispersion record is generated; Based on the mixed humidity dispersion record, the dispersion range is compared and the stabilizer ratio is adjusted, the electrostatic potential is measured at multiple points and the potential change is recorded, the ion wind jet head angle is corrected and the comparison results are collected to generate electrostatic monitoring data; Based on the electrostatic monitoring data, the electrostatic potential limit is confirmed and the stabilizer mixing uniformity is tested, the binder content is sampled and the humidity range is checked, the dispersed samples are reviewed and the key values ​​are recorded to generate the granulation product.

7. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps of obtaining the multilayer pressed body are: Based on the granulated product, wetting agent and β-cyclodextrin, compacting is performed in layers, compaction uniformity is detected and parameters of each layer are recorded, different pressure sections are controlled, alignment errors of upper and lower layers are confirmed and feeding amount is corrected, compaction equipment is operated at intervals and compaction density is collected to generate layered compaction records; Based on the layered pressing record, layer thickness comparison is performed and pressing uniformity data is checked, wetting agent content is sampled and values ​​are registered, β-cyclodextrin distribution is tested and a compaction structure list is formed, and pressing correction data is generated; Based on the pressing correction data, multi-stage pressure parameter comparison is performed and the feed rate is modified, the inter-layer ratio is reviewed and the layer thickness is confirmed, the pressing forming steady-state monitoring is performed and the strength of each layer is summarized to generate a multi-layer pressed body.

8. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps of obtaining the pulse forming body are: Based on the superposition of the multilayer pressed body, diatomaceous earth powder and hydroxyapatite, the pulse frequency and pressure are set, the temperature sensor is arranged and the instantaneous reading is monitored, the temperature change is detected and the tableting time is recorded, the pulse device is operated at intervals and the pressure peak is collected to generate a pulse pressing record; Based on the pulse suppression record, pulse frequency comparison is performed and impact interval is corrected, multi-point measurement of temperature sensor is performed and instantaneous readings are compared, pressure curve segmentation check is performed and pulse parameters are updated to generate temperature and pressure monitoring data; Based on the temperature and pressure monitoring data, the pressure peak value is compared with the instantaneous reading and the pulse frequency is corrected, the pulse duration is confirmed and the tableting stability information is recorded, the diatomaceous earth powder and hydroxyapatite stacking condition is reviewed, and a pulse molded body is generated.

9. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps for obtaining the humidity balance sheet are as follows: The pulse forming body is placed in a relative humidity range of 40 to 50, the humidity deviation is monitored at intervals, the dehumidification and humidification parameters are adjusted, the temperature fluctuation is recorded and compared with the reference value, the sensor is repeatedly sampled and the data list is corrected to generate the humidity monitoring record; Based on the humidity monitoring records, humidity deviation comparison is performed and the static time is updated, dehumidification device and humidification system switching operation is performed and parameter range is corrected, temperature fluctuation data is summarized multiple times and abnormal values ​​are identified to generate static summary data; Based on the static summary data, perform segmented analysis of humidity and temperature curves and supplement monitoring records, recheck deviation values ​​and troubleshoot abnormal fluctuations, confirm the switching of dehumidification and humidification devices and register the correction results to generate a humidity balance sheet.

10. The method for preparing the stable chlorine dioxide effervescent tablet according to claim 4, characterized in that: The steps of obtaining the prepared finished product are: Conduct appearance screening of moisture-balanced tablets and test tablet weight consistency and disintegration time, record stability indicators and compare pulse tableting parameter records, conduct tablet shape integrity and hardness tests and observe the outer layer crack conditions to generate appearance inspection data; Based on the appearance inspection data, tablet weight consistency comparison is performed and disintegration time information is checked, stability indicators are recorded multiple times and compared with pulse tableting parameters, outer layer crack conditions are re-screened and inspection results are summarized to generate finished product inspection records; Based on the finished product inspection record, the sheet hardness and outer layer crack data are compared and the screening results are confirmed, grouping and numbering and weighing operations are performed and batch files are integrated, and the record signing steps are performed and archived to obtain the prepared finished product.

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