Tablet product without flow aid and preparation method thereof

Abstract

The invention relates to a glidant-free tablet product and a preparation method thereof. According to the method, raw material powder is tableted to prepare a tablet product; wherein the raw material powder meets the following requirements: the D50 of the powder is 50-150 [mu] m; the particle size distribution width (D90-D10) / D50 of the powder is equal to 1.8-3; the bulk density of the powder is 0.4-0.5 g / cm < 3 >; the difference between the tap density and the bulk density of the powder is greater than or equal to 0.2 g / cm < 3 >; the tabletting process comprises the following steps: pre-pressing the raw material powder to obtain a pre-pressed molded body, and carrying out main pressing on the pre-pressed molded body. According to the method disclosed by the invention, the stable batch production of the glidant-free tablets can be realized.

Description

Technical Field

[0001] This invention relates to a tablet product without flow aids and its preparation method, belonging to the field of food processing technology. Background Technology

[0002] In solid dosage form production, tablets are the most commonly used dosage form due to their advantages such as accurate dosage, convenient administration, and good stability. To ensure a smooth tableting process and stable tablet quality, traditional tablet formulations typically require the addition of a certain proportion of glidants, such as silica, tricalcium phosphate, and magnesium stearate. The main function of these glidants is to reduce the internal friction between powder particles, improve flowability, and to a certain extent, provide lubrication and anti-adhesion effects.

[0003] However, due to certain specific needs (such as clean labeling, increased drug loading, avoidance of interactions with specific excipients, meeting special formulation requirements, or simplifying formulation composition), the development of tablets without any traditional gliders has become an important research direction in the industry. However, the development and production of glide-free tablets face the following three interrelated and difficult-to-solve core technical challenges: 1. Poor powder flowability: Due to the lack of a flow aid and the resulting "ball bearing" effect, the internal friction coefficient between powder particles increases significantly. This leads to poor material flow in the tablet press hopper, easily causing "bridging" or "retention," which in turn results in uneven filling of the tablet press die. This problem directly manifests as excessive tablet weight variation, with a relative standard deviation typically exceeding 5%, failing to meet the stringent requirements for tablet weight variation stipulated in regulations such as the Chinese Pharmacopoeia.

[0004] 2. Insufficient Powder Compressibility: Traditional gliding agents can enhance compressibility under certain conditions. In systems without gliding agents, the plastic deformation capacity of powders is often weak. During tableting, powder particles cannot effectively bind and rearrange, resulting in insufficient mechanical strength of the compressed tablets. This manifests as generally low tablet hardness (usually below 40N), and tablets are prone to cracking and loosening during tableting or subsequent processing, severely affecting product yield and quality.

[0005] 3. Poor stability of molding process: Powders without glidants are generally more sensitive to changes in temperature and humidity in the production environment. When the ambient temperature is above 28℃ or the relative humidity is above 50%, the powder, especially those containing hygroscopic components, easily absorbs moisture. This not only further deteriorates the powder's flowability but also leads to severe sticking (material adhering to the punch surface) and cracking (tablet breakage during demolding) during tableting. The combination of these problems results in a generally low batch yield of glidant-free tablets, often below 85%, causing significant production costs and material waste.

[0006] To address the aforementioned problems, existing technologies typically employ isolated, stopgap solutions. While these may temporarily alleviate certain symptoms, they fail to address the fundamental nature of powder properties. Therefore, existing technologies cannot completely resolve the flowability issue while simultaneously ensuring good compressibility and stable formability, thus hindering the stable and efficient industrial production of flow-free tablets.

[0007] Therefore, there is an urgent need in this field for a novel technical solution that can fundamentally improve the overall performance of non-fluidized powders, thereby developing a high-quality non-fluidized tablet with excellent flowability, compressibility, and process stability. Summary of the Invention

[0008] To address the aforementioned technical problems, the present invention aims to provide a method for preparing a tablet product without a flow aid, which enables stable mass production of tablets without a flow aid.

[0009] To achieve the above objectives, the present invention provides a method for preparing a tablet product without a flow aid, wherein the method involves compressing raw material powder to obtain a tablet product. The raw material powder meets the following requirements: the powder's D50 is 50-150 μm; the particle size distribution width (D90-D10) / D50 = 1.8-3; and the powder's bulk density is 0.4-0.5 g / cm³. 3 The difference between the tapped density and the loose density of the powder is greater than or equal to 0.2 g / cm³. 3 ; The tableting process includes pre-compressing the raw material powder to obtain a pre-compressed body, and then performing main compression on the pre-compressed body.

[0010] This invention reduces internal particle friction and improves the natural flowability of powders by controlling the properties of raw material powders, thereby reducing reliance on flow aids. The flow aid-free formulation of this invention refers to a formulation system that does not contain traditional flow aids such as silica, tricalcium phosphate, magnesium stearate, and talc.

[0011] According to a specific embodiment of the present invention, by controlling the D50 of the powder to 50-150 μm, the present invention can reduce the agglomeration of fine powder, reduce the adsorption force between particles, and decrease the angle of repose of the powder from 45° to below 40°, thereby improving the flowability. If the D50 of the powder is less than 50 μm, it will lead to an excessive amount of fine powder, causing agglomeration and resulting in the angle of repose of the powder exceeding 40°.

[0012] According to a specific embodiment of the present invention, by controlling the particle size distribution width (D90-D10) / D50 of the powder to be between 1.8 and 3, the powder has a high proportion of large-diameter particles and a small proportion of particles with large size differences. This is beneficial for the formation of a dense structure by large particles during the pressing process, while the small particles have a low volume proportion and can fill gaps, thus improving the tablet forming stability. The hardness of the prepared tablets can be increased from 40N to over 60N. If the particle size distribution width (D90-D10) / D50 < 1.8 or > 3, it will result in fewer large particles and more small particles, leading to poor tablet forming stability.

[0013] According to a specific embodiment of the present invention, the loose density of the powder is controlled to be 0.4-0.5 g / cm³. 3 This ensures that the raw material powder is fed evenly into the hopper.

[0014] According to a specific embodiment of the present invention, the difference between the tapped density and the loose density of the powder is controlled to be greater than or equal to 0.2 g / cm³. 3 Good compression molding results can be obtained by using a specific method. Furthermore, the greater the difference between the tapped density and the loose density, the higher the bonding potential between particles during compression, resulting in better compression molding. If the difference between the tapped density and the loose density is less than 0.2, the bonding potential between particles is low during compression, leading to poor compression molding.

[0015] According to a specific embodiment of the present invention, preferably, the moisture content of the powder is 2.0-3.0% by mass. By controlling the moisture content within a suitable range, the plastic deformation ability of the particles can be enhanced, and the bonding can be promoted. In particular, for powders with high fat content, it can improve the tablet separation phenomenon caused by their strong hydrophobicity.

[0016] According to a specific embodiment of the present invention, the tableting process of the present invention can employ two processes: pre-compression and main compression. This two-step compression (pre-compression-main compression) reduces the elastic recovery of the tablets and optimizes particle density uniformity, reducing stress concentration during tableting and lowering the risk of tablet cracking. Preferably, the pre-compression pressure is 2-4 kN, and the main compression pressure is preferably 8-12 kN.

[0017] According to a specific embodiment of the present invention, preferably, the tableting speed is 100,000-180,000 tablets / hour.

[0018] According to a specific embodiment of the present invention, preferably, the tablet press uses a hopper with a consistent upper and lower pipe diameter, and employs a high-frequency, low-amplitude rotary vibration of 200-500Hz during the feeding process. Using a hopper with a consistent upper and lower pipe diameter forces the powder to achieve uniform speed during transport, eliminating dead zones or sudden changes in flow velocity within the flow channel, and ensuring stable operation of downstream equipment. During the feeding process, the high-frequency, low-amplitude rotary vibration of 200-500Hz (generated by an eccentric shaft or electromagnetic exciter) transfers vibration energy to the flow channel wall, preventing fluid particles from adhering to the pipe wall and forming a "scaling layer," while further disrupting locally stagnant fluid areas. The tablet press, with the aforementioned hopper design and rotary vibration treatment, can break down interparticle forces and "bridge" structures, avoiding "bridging" phenomena, resolving blockages and weight fluctuations, and enabling continuous tablet pressing for 12 hours without downtime. This solves the problems of material retention and uneven filling, further improving tablet weight stability.

[0019] According to a specific embodiment of the present invention, preferably, the raw material powder is obtained by mixing two or more powders, and the temperature during the mixing process is controlled at 18-27℃ (preferably 20-25℃), and the humidity is controlled at 38-52% (preferably 40-50%).

[0020] According to a specific embodiment of the present invention, preferably, the temperature during the tableting process is controlled at 20-25°C and the humidity is controlled at 40-50% (±2% fluctuation).

[0021] According to a specific embodiment of the present invention, by controlling the temperature and humidity in the mixing and tableting areas, the influence of environmental factors on the hygroscopicity of the powder can be eliminated, avoiding defects such as sticking and cracking. If the temperature and humidity exceed the range of 20-25℃ and 40-50%, defects such as high sticking rate and cracking will occur. For example, when the humidity is >60%, the powder is prone to hygroscopicity, and the sticking rate is >5%.

[0022] Specifically, infrared moisture meters (accuracy ±0.2%) and temperature and humidity sensors can be installed in the dry mixing room and tableting room to provide real-time feedback of temperature and humidity values, so as to achieve real-time adjustment of temperature and humidity.

[0023] According to a specific embodiment of the present invention, the powder contains nano-sized calcium carbonate (preferably added at 1-15‰ of the total mass of the tablet raw materials), which can further improve the hardness (+10 N).

[0024] According to a specific embodiment of the present invention, preferably, the method further includes a coating step, which can improve the appearance of the tablets. Specific coating materials and methods can be found in conventional practices in the art.

[0025] The present invention also provides a tablet product without a flow aid, which is prepared by the above method.

[0026] According to a specific embodiment of the present invention, preferably, the tablet product is a milk tablet, milk shell, effervescent tablet, compressed candy, tablet nutritional supplement, chewable tablet, milk-containing solid molded product, etc.

[0027] According to a specific embodiment of the present invention, preferably, the above-mentioned tablet product is a milk tablet, and the filler is glucose, solid corn syrup, erythritol, xylitol, sorbitol, maltitol, etc.

[0028] According to a specific embodiment of the present invention, preferably, the above-mentioned tablet product is a chewable tablet, and the crispness can be improved by adjusting the ratio of sweetener and filler.

[0029] According to a specific embodiment of the present invention, preferably, the above-mentioned tablet product is an effervescent tablet, and the filler can be replaced with a sodium bicarbonate-citric acid system. The method of the present invention can solve the problem of effervescent granules easily absorbing moisture and clumping.

[0030] To address the bottlenecks in existing technologies, this invention constructs a systematic solution from the dimensions of raw material powder characteristic control, process parameter matching, and environmental closed-loop control. Through the coordinated control of multiple powder characteristic parameters (particle size distribution, bulk density, tapped density, the difference between tapped density and bulk density, and moisture content) and the online closed-loop control logic of temperature, humidity, and moisture, it achieves stable batch production of glidant-free tablets.

[0031] The technical solution of the present invention can achieve the technical effects shown in Table 1 below: Table 1: Detailed Implementation

[0032] In order to provide a clearer understanding of the technical features, objectives and beneficial effects of the present invention, the technical solution of the present invention will now be described in detail below, but it should not be construed as limiting the scope of implementation of the present invention.

[0033] Example 1: Active probiotic milk tablets under optimal processing conditions

[0034] The active probiotic milk tablets provided in this embodiment contain the following (by weight percentage): Probiotic powder (active bacteria count ≥10) 8 CFU / g): 0.1% Edible glucose powder: 14.9% Whole milk powder: 85%; The whole milk powder has a powder D50 of 80 μm, a particle size distribution width (D90-D10) / D50 of 2.2, and a bulk density of 0.45 g / cm³.3 Tapped density - Loose density = 0.5 g / cm³ 3 Moisture content = 2.5%.

[0035] These active probiotic milk tablets are prepared through the following steps: Whole milk powder, probiotic powder, and edible glucose powder are premixed and then dry-mixed to obtain a mixed powder. The mixed powder is pre-pressed and then main-pressed to obtain active probiotic milk tablets.

[0036] Tableting process: Tableting speed = 120,000 tablets / hour, main pressure = 10kN, pre-compression pressure = 3kN; Equipment and Environment: The system uses a hopper with the same upper and lower pipe diameters and a high-energy vortex flow aid (frequency 400Hz). The ambient temperature is 23℃±2℃ and the humidity is 45%±2%.

[0037] Test results: The powder repose angle is 35°, the tablet hardness is 75N, the tablet weight variation RSD is 1.2%, the viable bacteria survival rate (after tableting) is 92%, and the batch qualification rate is 100%.

[0038] Effect analysis: By controlling the powder D50 to 50-150μm and the bulk density to 0.4-0.5g / cm³, 3 With a tap density difference ≥0.2, combined with equipment optimization, the flowability (angle of repose 35°) and compressibility (hardness 75N) are synergistically improved, and the probiotic activity loss rate is <8%.

[0039] Example 2: Chewable tablets requiring high hardness (adjusting the compression pressure)

[0040] Formula composition: Probiotic powder (active bacteria count ≥10) 8 CFU / g): 0.2%; Edible glucose powder: 11.8%; Whole milk powder: 80%; Freeze-dried strawberry powder: 8%.

[0041] This chewable tablet, which requires high hardness, is prepared through the following steps: Whole milk powder, probiotic powder, edible glucose powder, and freeze-dried strawberry powder are premixed and then dry-mixed to obtain a mixed powder. The mixed powder is pre-compressed and then main-compressed to obtain chewable tablets with high hardness requirements.

[0042] Key process parameters: Main pressure = 12kN, preload pressure = 4kN; The mixed powder has a D50 of 100 μm, a particle size distribution width (D90-D10) / D50 of 2, and a bulk density of 0.55 g / cm³. 3 Tapped density - Loose density = 0.4 g / cm³ 3 Moisture content = 2.6%.

[0043] Test results: Tablet hardness = 90N, friability = 0.2%, angle of repose = 32° (still meets flowability requirements).

[0044] Example 3: Adaptability verification in high temperature and high humidity environments

[0045] Formula composition: Same as Example 1; Environmental conditions: Temperature = 25℃ ± 2℃, Humidity = 50% ± 2% (close to the upper limit); Preparation process and other conditions: Same as in Example 1.

[0046] Test results: The powder's moisture absorption weight gain was 0.8% (24 hours), the stickiness rate was 0.05%, and the tablet weight difference RSD was 1.8%.

[0047] Comparative Example 1: Uncontrolled powder properties (Prior art)

[0048] The formulation and preparation process of this comparative example are the same as those of Example 1. The difference between the two is that the powder characteristics of this comparative example are not controlled, as detailed below: Powder D50 = 40 μm (< 50 μm), particle size distribution width = 3.5 (> 3), bulk density = 0.65 g / cm³ 3 The difference between the tapped density and the loose density is 0.15 g / cm³. 3 (<0.2g / cm) 3 ), moisture=1.5% (<2.0%).

[0049] Test results: The powder has an angle of repose of 43° (poor flowability), a tablet hardness of 35N (loose tablets), a tablet weight variation RSD of 4.8%, and a batch pass rate of 78%.

[0050] Comparative Example 2: Using a conventional flow aid (conflicting with the "flow aid-free" principle of this invention)

[0051] The formulation and preparation process of this comparative example are the same as those of Example 1. The difference between the two is that silica (0.2%) is added as a flow aid.

[0052] Test results: The powder has an angle of repose of 46° (good flowability), but the survival rate of probiotics drops to 75% (due to bacterial damage caused by adsorption of flow aid), which does not meet the requirements of the cleaning label.

[0053] Comparative Example 3: Excessive moisture content

[0054] The formulation and preparation process of this comparative example are the same as those of Example 1. The difference between the two is that the moisture content of this comparative example exceeds the standard, as follows: the moisture content of the mixed powder is 4.0% (>3.0%).

[0055] Test results: The powder clumps severely, the angle of repose is 42°, the sticking rate during tableting is 8%, and the tablet weight difference RSD is 4.5%.

[0056] Comparative Example 4: Uncontrolled Ambient Humidity

[0057] The formulation and preparation process of this comparative example are the same as those of Example 1. The difference between the two is that the environmental humidity of this comparative example is out of control, as follows: environmental humidity = 60% (>50%), and other parameters are the same as those of Example 1.

[0058] Test results: Powder moisture absorption weight gain = 3.2%, sticking rate = 12%, batch pass rate = 82%.

[0059] Comparative Example 5: The formulation and preparation process of this comparative example are the same as those of Example 1. The difference between the two is that the feeding hopper of the tablet press in this comparative example adopts a structure that is larger at the top and smaller at the bottom, and no vortex flow aid is performed during the feeding process.

[0060] Test results: The tablet weight was unstable, with a tablet weight variation RSD of 4.5% and a batch pass rate of 85%.

[0061] II. Results Verification

[0062] Necessity of core parameters: Examples 1-3 verified the powder D50 (50-150μm) and bulk density (0.4-0.5g / cm³). 3 The difference between tapped density and loose density is ≥0.2 g / cm³. 3 The synergistic effect of moisture (2.0-3.0%) and ambient temperature and humidity (20-25℃ / 40-50%) was demonstrated in Comparative Examples 1-4, showing that deviations from the parameter range would lead to a significant decrease in flowability, compressibility, or stability. Comparative Example 5 demonstrated that not using a hopper with consistent upper and lower pipe diameters and high-energy vortex flow aid would result in unstable tablet gram weight.

[0063] Advantages of no flow aid: A comparison of Example 1 and Comparative Example 2 shows that, without introducing a flow aid, the present invention achieves flowability comparable to traditional flow aids through powder property control, while avoiding loss of active ingredients and increasing the survival rate of probiotics by 17%. Universality: Examples 2-3 show that by adjusting the formulation ratio and process parameters (such as tableting pressure), different product requirements (high hardness, environmental adaptability) can be met.

[0064] Test method description: 1. Survival rate of live bacteria (after tableting) The survival rate is calculated by measuring the number of viable bacteria in the powder before tableting and the number of viable bacteria in the tablet after tableting using the microbial counting method.

[0065] 2. Batch pass rate

[0066] The batch pass rate is calculated by inspecting the quality indicators of a single production batch and then calculating the proportion of qualified batches to the total number of inspected batches.

[0067] 3. Powder absorbs moisture and increases in weight.

[0068] Test Principles

[0069] Under constant temperature and humidity conditions, the amount of water absorbed by the powder within a specified time is measured, and the moisture absorption weight gain rate is calculated to reflect the hygroscopicity of the powder (the greater the weight gain rate, the stronger the hygroscopicity).

[0070] Operating steps: Step 1: Sample pretreatment (drying to constant weight) Objective: To remove the original moisture from the powder and ensure that subsequent weight gain comes only from the moisture absorption process.

[0071] Procedure: Take a certain amount of powder (e.g., 5-10g) and dry it in an oven / vacuum drying oven (temperature depends on the properties of the powder, e.g., 60℃). Weigh it once every hour until the difference between two weighings is ≤0.0002g (constant weight). Record the weight at this point as W0 (initial weight after drying).

[0072] Step 2: Moisture absorption test (controlling ambient humidity)

[0073] Objective: To allow the powder to fully absorb moisture and reach equilibrium under specified humidity conditions.

[0074] Procedure: Place the dried sample in a constant humidity environment (e.g., using saturated salt solutions: sodium chloride saturated solution → 75%RH, potassium nitrate → 92%RH) for 24-48 hours, weighing it every 8 hours until the weight no longer changes (constant weight). Record this weight as W1 (final weight after moisture absorption).

[0075] Step 3: Calculate the moisture absorption weight gain rate: Moisture absorption weight gain rate (%) = [(W1-W0) / W0]×100%.

[0076] 4. The tests for powder angle of repose, tablet hardness, tablet weight variation RSD, friability, and stickiness shall be performed in accordance with the usual practices in this field.

Claims

1. A method for preparing a tablet product without a flow aid, wherein, This method involves compressing raw material powder into tablets to obtain tablet products. The raw material powder meets the following requirements: the powder's D50 is 50-150 μm; the particle size distribution width (D90-D10) / D50 = 1.8-3; and the powder's bulk density is 0.4-0.5 g / cm³. 3 The difference between the tapped density and the loose density of the powder is greater than or equal to 0.2 g / cm³. 3 ; The tableting process includes pre-compressing the raw material powder to obtain a pre-compressed body, and then performing main compression on the pre-compressed body.

2. The preparation method according to claim 1, wherein, The moisture content of the powder is 2.0-3.0% by mass.

3. The preparation method according to claim 1, wherein, The pre-compression pressure is 2-4 kN.

4. The preparation method according to claim 1 or 3, wherein, The main pressure is 8-12 kN.

5. The preparation method according to claim 1, wherein, The tableting speed is 100,000 to 180,000 tablets per hour.

6. The preparation method according to claim 1, wherein, The tablet press uses a hopper with a consistent upper and lower pipe diameter, and employs a high-frequency, low-amplitude rotary vibration of 200-500Hz during the feeding process.

7. The preparation method according to claim 1, wherein, The raw material powder is obtained by mixing two or more powders, and the temperature during the mixing process is controlled at 18-27℃ and the humidity is controlled at 38-52%.

8. The preparation method according to claim 1, wherein, The temperature during the tableting process is controlled at 18-27℃, and the humidity is controlled at 38-52%.

9. A tablet product without a flow aid, prepared by the method according to any one of claims 1-8.

10. The tablet product according to claim 9, wherein, The tablet product is a milk tablet, milk shell, effervescent tablet, compressed candy, tablet nutritional supplement, chewable tablet, or milk-containing solid molded product.

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