Dry granulation process of traditional Chinese medicine decoction piece extract powder containing fatty oil

Abstract

The invention discloses a dry granulation process of fatty oil-containing traditional Chinese medicine decoction piece extract powder, which comprises the following steps: uniformly mixing the extract powder of fatty oil-containing traditional Chinese medicine decoction pieces with the total fatty oil content of 1-200mgg <-1 > and a filler, then pressing the uniformly mixed powder into strips by using a dry granulation machine, and crushing and sieving, thereby obtaining the fatty oil-containing traditional Chinese medicine decoction piece extract powder, the filling agent comprises cyclodextrin; the technological parameters of the dry granulation are as follows: the using amount of the filler is 10-80% of the total material mass, the pressure of a roller is 30-200bar, and the rotating speed of the roller is 2-10rpm. According to the method, the caking strength, the particle forming rate, the particle friability, the particle bulk density, the particle repose angle and the particle dissolubility of the extract powder after the filler is added are taken as evaluation indexes, the process parameters of dry granulation of the fatty oil-containing traditional Chinese medicine decoction piece extract powder are optimized by adopting a single-factor test and an orthogonal test, the process is stable and feasible, and the obtained particles are high in drug loading capacity and good in stability. The flowability is good, the hardness is moderate, and a reference is provided for large-scale application of a dry granulation process of the fatty oil-containing traditional Chinese medicine decoction piece extract powder.

Description

Technical Field

[0001] The invention belongs to the technical field of dry granulation, and in particular relates to a dry granulation process of a Chinese herbal medicine extract powder containing fatty oil. Background Art

[0002] The dry granulation method for preparing Chinese medicine preparations (such as granules and tablets) has the advantage that the extract powder can be agglomerated without a liquid binder, which can minimize the impact of materials, water and heat on the preparation process and drug ingredients, and improve the stability of the preparation process. Among them, the roller compaction method is a commonly used method in dry granulation.

[0003] Traditional Chinese medicine has complex ingredients. Extract powders of Chinese herbal medicines rich in polysaccharides and organic acids are easy to absorb moisture and have high viscosity. When dry granulation is performed, they stick to the wheel, and the yield of strips and particles is low, such as Cornus officinalis. Another type of extract powder contains rich fatty oils, has low viscosity, is difficult to form strips during dry granulation, and has a low particle yield, such as Semen Ziziphi Spinosae and Semen Coix. At present, most of the research focuses on how to solve the problem of sticking to the wheel during dry granulation, such as adding lubricants, using fillers with higher glass transition temperatures, and reducing the surface temperature of the rollers. However, there are few reports on the dry granulation process of extract powders of Chinese herbal medicines rich in fatty oils.

[0004] Invention patent CN102058624A discloses a method for improving the dry granulation formability and particle quality of Chinese medicine formula granules. The method is to add maltodextrin with a hydrolysis degree of 16 to 20 as an auxiliary material before dry granulation to improve the compressibility of rhizomes, fruit seeds and animal Chinese medicine extract powders with high contents of starch, fatty oil, animal protein, mucus, etc., and to improve the dry granulation particle forming rate. Then, a certain amount of micro-powder silica gel is added after the granules are made to solve the shortcomings of high granule moisture absorption and easy wall adhesion caused by excessive hydrolysis of maltodextrin. Although this patent is based on solving the problem of improving the dry granulation effect of Chinese herbal extract powders of rhizomes, fruit seeds and animals with high contents of starch, fatty oil, animal protein, mucus, etc., its emphasis is on improving the particle forming rate by improving the compressibility of the extract powder. Moreover, the scope of its application of Chinese herbal medicines is too large, and it does not focus on solving the problem of dry granulation process of extract powders of Chinese herbal medicines rich in fatty oil. The patent also does not give examples of such Chinese herbal medicines. Summary of the invention

[0005] The first object of the present invention is to provide a dry granulation process for extract powder of traditional Chinese medicine slices containing fatty oil, wherein a filler is added to the extract powder and then dry granulation is performed, and the filler is screened by taking the agglomeration strength of the extract powder after adding the filler, the particle forming rate, the particle friability, the particle bulk density, the particle repose angle and the particle solubility as evaluation indicators, and a process for using cyclodextrin as the filler is obtained.

[0006] The second purpose of the present invention is to solve the problem of high price of filler cyclodextrin and provide a method for using cyclodextrin together with low-priced maltodextrin, so as to achieve a granulation effect equivalent to that of using β-cyclodextrin alone by optimizing the ratio of the two and the granulation process parameters, so as to reduce production costs.

[0007] The third object of the present invention is to use cyclodextrin and maltodextrin as fillers, and optimize the dry granulation parameters by single factor and orthogonal test combined with specific weight scores.

[0008] The technical solution of the present invention is as follows: A dry granulation process for extract powder of Chinese herbal medicine slices containing fatty oil comprises the following steps: uniformly mixing the extract powder of Chinese herbal medicine slices containing fatty oil with a filler, and then pressing the uniformly mixed powder into strips by a dry granulator, and then crushing and sieving.

[0009] The total fatty oil content of the extract powder is 1-200 mg•g -1 , preferably 10~50 mg•g -1 The filler includes cyclodextrin, preferably β-cyclodextrin.

[0010] The conditions for dry granulation include: the amount of filler is 10~80% of the total material mass, the roller pressure is 30~200bar, and the roller speed is 2~10 rpm.

[0011] Preferably, the filler comprises cyclodextrin and maltodextrin, and the mass ratio of the two is (5-3): (2-1). Preferably, the mass ratio of cyclodextrin and maltodextrin is (2-4): 1. The DE value of the maltodextrin is 5-20.

[0012] Preferably, the conditions for dry granulation also include: the diameter of the roller is 120 mm, the width is 20 mm, the roller spacing is controlled to be 1.5 mm using a screw negative feedback system, the feeding speed is 18-20 rpm, and the granulation frequency is 20-40 Hz.

[0013] Preferably, the particle size parameter of the extract powder is: D 50 35~50μm, D 90 90~110μm.

[0014] Preferably, the granules obtained by granulation of the present invention, measured according to the particle size and particle size distribution determination method (General Rule 0982 Method 2 Double Screening Method), the sum of the particles that cannot pass through the No. 1 sieve and the particles that can pass through the No. 5 sieve shall not exceed 15%.

[0015] The present invention also provides a method for optimizing the process parameters of the dry granulation, comprising the following steps: first, according to a single factor experiment, the key factors to be examined are screened out with the agglomeration strength of the extract powder after adding a filler, the particle forming rate, the particle friability, the particle bulk density, the particle angle of repose, and the particle solubility as basic indicators; then, an orthogonal experiment is designed based on the key factors to take the agglomeration strength of the extract powder after adding a filler, the particle forming rate, and the particle friability as comprehensive evaluation indicators, different weights are set for comprehensive scoring, and the dry granulation process parameters are optimized.

[0016] Preferably, the single factors include filler type, mass ratio of cyclodextrin to maltodextrin, mass ratio of extract powder to filler, correlation between agglomeration strength of extract powder and particle index after adding filler, roller pressure and roller speed.

[0017] Preferably, the key factors screened out are filler dosage, roller pressure and roller speed.

[0018] Preferably, the weights of the comprehensive evaluation indexes are: the agglomeration strength of the extract powder after adding the filler is 0.3, the particle forming rate is 0.4, and the particle friability is 0.3.

[0019] Preferably, the comprehensive score calculation method is: comprehensive score = (test value of extract powder agglomeration strength after adding filler / maximum value of extract powder agglomeration strength after adding filler within the group) × 0.3 + (particle forming rate test value / maximum value of particle forming rate within the group) × 0.4 - (particle friability test value / maximum value of particle friability within the group) × 0.3.

[0020] Preferably, the optimized dry granulation process parameters are: the amount of the filler is 30-40% of the total material mass, the roller pressure is 80-100 bar, and the roller speed is 2.8-3.8 rpm.

[0021] Beneficial effects of the present invention: 1. In the dry granulation pressing process, particles are rearranged, deformed, broken, and bonded to form strips under pressure. However, the extract powder of Chinese herbal medicine slices containing fatty oil has poor adhesion and is difficult to form strips. The main reason is that the extract powder of Chinese herbal medicine slices containing fatty oil (such as coix seed) contains some oily components. Such compounds can form a lubricating film on the surface of the particles, which significantly reduces the cohesion and friction between the particles. Even at a higher roller pressure, it is difficult to form embryos. β-cyclodextrin is an excellent filler that can improve the tensile strength of tablets and reduce the yield pressure of materials. Its deformation mechanism is mainly plastic deformation. The present invention solves the industry loopholes about dry granulation of extract powder of Chinese herbal medicine slices containing fatty oil by adding filler cyclodextrin to the extract powder of Chinese herbal medicine slices containing fatty oil and then performing dry granulation, and optimizes the dry granulation process, providing a reference for the large-scale application of dry granulation of extract powder of Chinese herbal medicine slices containing fatty oil.

[0022] 2. Maltodextrin is cheap and has good viscosity and compression molding properties when solid preparations are formed. The present invention uses cyclodextrin and cheap maltodextrin together as fillers, optimizes the ratio of the two and granulation process parameters to achieve a better granulation effect, reduces production costs, and reduces the amount of filler. The obtained particles have a high drug loading, good fluidity, and moderate hardness. In addition, the experiment found that no lubricant was added during dry granulation, the pressing process was smooth, and there was no sticking phenomenon, which also shows that the Chinese herbal medicine extract powder containing fatty oil has a good lubricating effect.

[0023] 3. After adding filler to the extract powder of Chinese herbal medicine slices containing fatty oil, the present invention uses a texture analyzer to test the agglomeration strength index, and combines the particle forming rate, friability, bulk density, angle of repose and other indicators, adopts a single factor experiment to screen the key influencing factors such as filler type and roller pressure, optimizes the dry granulation process parameters by an orthogonal test method, and determines a method for determining better dry granulation parameters in combination with specific weight scores. After multiple verifications, it is shown that the dry granulation process is stable and feasible, and the method for determining the parameters is reasonable and feasible. DETAILED DESCRIPTION

[0024] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. 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.

[0025] Unless otherwise specified, the reagents involved in the embodiments of the present invention are all commercially available products and can be purchased through commercial channels.

[0026] The invention provides a dry granulation process for extract powder of Chinese herbal medicine slices containing fatty oil, comprising the following steps: uniformly mixing the extract powder of Chinese herbal medicine slices containing fatty oil with a filler, and then pressing the uniformly mixed powder into strips by a dry granulator, and then crushing and sieving.

[0027] 1. Instruments and Materials BT120 dry granulator (Alexanderwerk, Germany), electric constant temperature blast drying oven (Shanghai Yuejin Medical Instrument Factory), ML3002E / 02 electronic balance (Mettler-Toledo Instrument Co., Ltd.), JZ-7 and JL-A3 powder property testers (Chengdu New Powder Company), TA.HD PLUS texture analyzer (Stable Micro Systems, UK).

[0028] Microcrystalline cellulose (MCC), lactose, soluble starch, dextrin, maltodextrin DE15, β-cyclodextrin (β-CD), hydroxypropyl methylcellulose (HPMC), povidone k30 (PVP k30), coix seed extract powder, and defatted coix seed extract powder were all purchased through conventional channels.

[0029] 2. Test methods 1. Determination of basic indicators (1) Powder agglomeration strength The agglomeration property of powder can be used to evaluate the tendency of powder stress change and the strength of agglomeration when the powder is subjected to pressure. The test was conducted using the Poweder Flow Analyser program in the texture analyzer with a PFA probe of 23 mm in diameter. The test is divided into two parts: pre-mixing and formal mixing. First, the stirring paddle on the instrument will pre-mix the sample in the experimental cup twice to make the powder uniform. Then, five formal compression and mixing will be performed with a compression force of 750 g and a stirring speed of 10 mm / s to simulate the sample agglomeration process. The stirring paddle is compressed downward and the powder gradually agglomerates under the force. At the end of the fifth compression, the agglomerate has been formed. The stirring paddle is lifted upward according to the set program to shear and break the consolidated powder and measure the work required to shear the agglomerated powder (the area of ​​the red area under the curve), which is the agglomeration strength (g•cm -3 ), the agglomeration strength is automatically obtained by the internal algorithm of the instrument. In the present invention, the agglomeration strength of two kinds of powders, namely, coix seed extract powder and coix seed extract powder with filler added, is measured respectively.

[0030] (2) Particle forming rate The particle forming rate was determined by the double sieving method. The mass of particles that could pass through the No. 1 sieve and the mass of particles that could not pass through the No. 5 sieve were weighed respectively, and the particle forming rate (%) was calculated according to formula (1).

[0031]

[0032] (3) Particle friability Weigh 10 g of particles that pass through the No. 2 sieve but not through the No. 3 sieve, accurately weigh the mass (m1), place in a friability tester, add 200 glass rollers, rotate for 4 min, and rotate at a speed of 100 r•min -1 After the rotation is completed, take out the particles, pass them through the No. 3 sieve, weigh the mass of the particles that do not pass through the No. 3 sieve (m2), and calculate the friability (%) according to formula (2). Repeat three times.

[0033]

[0034] (4) Particle bulk density Weigh 3 g of particles and place them in a 10 ml measuring cylinder. Tap the outer wall of the measuring cylinder to make the particles settle tightly at the bottom of the measuring cylinder. Read the volume (v), weigh the particle weight (m), and calculate the bulk density (g•cm) according to formula (3). -3 ), repeated three times and calculated the average value.

[0035]

[0036] (5) Particle repose angle Using the fixed funnel method, a cone sample is formed by dropping from a funnel with a taper of 60° onto a horizontal metal plate below. The cone radius (r) and cone height (H) are recorded, and the angle of repose (θ) of the sample is calculated according to formula (4). Repeat three times and calculate the average value.

[0037]

[0038] (6) Particle solubility Check according to the solubility test method of the National Drug Standards for Chinese Medicine Formula Granules. Boil 200 ml of hot water, add 10 g of weighed granules, keep boiling, stir for 5 minutes, and observe immediately. It should be completely dissolved or slightly turbid, without burnt debris or foreign matter.

[0039] 2. Determination of total fatty oil content in extract powder Take an appropriate amount of coix seed extract powder, accurately weigh the mass (m1), place it in the filter paper tube of the Soxhlet extractor, add petroleum ether (60~90℃) in a round-bottom flask, heat and reflux to extract (5 hours) until the fatty oil is completely extracted, collect the extract and place it in a constant weight evaporating dish. Accurately weigh the mass of the empty evaporating dish (m2), evaporate to dryness at low temperature in a water bath, dry at 100℃ for 1 hour, move to a desiccator, cool for 30 minutes, accurately weigh the mass (m3), calculate the fatty oil content of the sample (the mass of fatty oil contained in every 1g of extract powder) according to formula (5), repeat three times and calculate the average value.

[0040]

[0041] 3. Granule preparation (basic process of dry granulation) Take two kinds of powders, namely, coix seed extract powder and coix seed extract powder with filler (filler dosage 50%), and prepare granules respectively. Press the powders into strips using a dry granulator. Each powder is 300 g. Crush them with a crusher and collect the granules between sieves No. 1 and No. 5. Determine the basic indicators under item 1 of this part.

[0042] Dry pressing conditions: The diameter of the roller is 120 mm and the width is 20 mm. The hydraulic pressure (roller pressure) selection range is 80 bar. The roller spacing is controlled by the screw negative feedback system to be 1.5 mm. The roller speed is 2.8 rpm•min. -1 , feeding speed 18.7 rpm·min -1 , the whole grain frequency is 30Hz. The ambient temperature is 20℃ and the relative humidity is 30%±5%.

[0043] 4. Data processing Excel 2010 was used to summarize and process the data; Origin 2021 was used to analyze the variance and range of the orthogonal experiment, and P < 0.05 was considered a significant difference; IBM SPSS Statistics 21 was used for correlation analysis, and P < 0.01 was considered an extremely significant difference.

[0044] 3. Experimental process and results 1. Comparison of properties of coix seed extract powder before and after defatting The coix seed extract powder before and after defatting was used to prepare granules according to the method under Part 2, Item 3, and the basic indicators under Part 2, Item 1 were measured. The results are shown in Table 1 (n=3).

[0045] Table 1

[0046] As shown in Table 1, the agglomeration strength of coix seed extract powder after defatting is significantly improved, the particle size becomes larger, the bulk density after granulation is increased, and the angle of repose is reduced. Undefatted coix seed extract powder is difficult to be directly made into granules. After defatting, coix seed extract powder can be made into a small amount of granules without adding fillers, but the granule strength is poor, indicating that fatty oil is one of the main reasons affecting granule formation. Therefore, choosing a suitable filler is very necessary for granule formation.

[0047] 2. Single Factor Test (1) Filler type screening Weigh each type of filler according to Table 2 below, mix evenly with coix seed extract powder, prepare granules according to the method under Part 2, Item 3, measure various basic indicators, and the results are shown in Table 2 (n=3).

[0048] Table 2

[0049] As shown in Table 2, the solubility test of granules containing MCC, soluble starch, dextrin, and HPMC failed. Except for povidone k30, the bulk density of the remaining filler granules is basically the same. The repose angle of all granules is slightly greater than 40°, indicating that the fluidity is poor. Attention should be paid to stirring or adding flow aids when packaging the granules. The effect of fillers on improving the agglomeration strength of powders is: β-CD> maltodextrin> lactose> MCC> PVP k30> HPMC> dextrin> soluble starch. The order of the molding rate is consistent with the order of the agglomeration strength. Except for lactose, the brittleness of other granules is consistent with the order of the molding rate.

[0050] The above results show that β-CD is the best filler for coix seed granules, but its disadvantage is that it is expensive. Maltodextrin and lactose can also be selected, but the price of lactose is high, and some patients may be lactose intolerant. Therefore, another object of the present invention is to select β-CD and inexpensive maltodextrin for use together, hoping to achieve the granulation effect of using β-CD alone by optimizing the ratio of the two and the granulation process parameters, so as to reduce the production cost.

[0051] (2) Screening of mass ratio of β-CD and maltodextrin Take β-CD and maltodextrin according to the mass ratio in Table 3 below, prepare particles according to the method under Part 2, Item 3, and measure various basic indicators. The results are shown in Table 3 (n=3).

[0052] Table 3

[0053] As can be seen from Table 3, when the ratio of β-CD to maltodextrin is 1:1, the agglomeration strength and forming rate are lower than other ratios, and the friability, bulk density and angle of repose are greater than other ratios, showing a poor granulation effect. When the addition ratio of maltodextrin is reduced, the agglomeration strength and forming rate of β-CD to maltodextrin ratio is 2:1~4:1, the friability, bulk density and angle of repose are lower, and the various indicators are very close, showing a good granulation effect. It can be seen from the friability indexes in Tables 2 and 3 that the addition of maltodextrin can also reduce the friability of the particles, thereby improving the seismic and wear resistance. When the addition ratio of maltodextrin continues to decrease, the agglomeration strength of β-CD to maltodextrin ratio of 5:1~6:1 begins to gradually decrease, and the friability gradually increases, showing a deterioration of the granulation effect. Therefore, the mass ratio of β-CD to maltodextrin in the filler is preferably 2:1~4:1. Since the cost is lower when the mass ratio is 2:1, this ratio is selected as the test basis for the other single-factor tests below.

[0054] (3) Filler dosage screening The amount of filler used in the present invention refers to the amount of filler used in the total material made of extract powder and filler, expressed as a percentage by mass. Reducing the amount of filler used is of great significance to the production and administration of granules. According to Table 4, the filler amount conditions in the granule preparation method under Part II, Item 3 were adjusted, and the mass ratio of β-CD to maltodextrin in the filler was adjusted to 2:1. After preparing coix seed granules, various basic indicators were measured, and the results are shown in Table 4 (n=3).

[0055] Table 4

[0056] As shown in Table 4, as the amount of filler increases, the agglomeration strength and molding rate gradually decrease, while the brittleness is the opposite. When the filler content is 40% and 30%, the differences in the indicators are not obvious. Since the cost is lower when the filler content is 30%, this content is selected as the test basis for the following other single factor tests.

[0057] (4) Correlation analysis between the agglomeration strength and particle index of extract powder after adding filler The Pearson correlation analysis method was used to conduct a correlation analysis between the powder agglomeration strength data and the particle indicators in the above single factor test. The results are shown in Table 5.

[0058] Table 5

[0059] .

[0060] As shown in Table 5, the agglomeration strength of the powder is highly significantly positively correlated with the particle forming rate (P < 0.01), indicating that more particles can be obtained when the powder with higher agglomeration strength is dry pressed. The agglomeration strength of the powder is highly significantly negatively correlated with the friability, bulk density and angle of repose of the particles (P < 0.01), indicating that the particles made of powder with higher agglomeration strength have greater bulk density, fluidity and strength, indicating that agglomeration strength may be a useful indicator for characterizing the properties of oil-rich extract powder.

[0061] (5) Roller pressure inspection The roller pressure conditions in the particle preparation method under Part II, Item 3 were adjusted according to Table 6, the amount of filler was adjusted to 30%, the mass ratio of β-CD to maltodextrin in the filler was adjusted to 2:1, and the basic indicators were measured after preparing coix seed granules. The results are shown in Table 6 (n=3).

[0062] Table 6

[0063] As shown in Table 6, when the roller pressure increases, the particle forming rate increases and the particle friability decreases. The reason is that the increase in roller pressure helps the material particles to undergo plastic deformation, making the particles more firmly bonded. Therefore, the particle strength increases, the forming rate increases, the friability decreases, the fine powder between particles decreases, and the angle of repose and bulk density decrease. When the pressure is between 80 bar and 100 bar, the forming rate and friability do not change significantly. The reason is that in the dry granulation process, there is a critical point for the roller pressure. Below the critical point, the particle forming rate increases significantly with the increase in pressure, while the friability decreases significantly. After exceeding the critical point, the forming rate increases slowly and the friability decreases slowly. Therefore, it is very important to determine a reasonable roller pressure during dry granulation.

[0064] (6) Roller speed inspection The roller speed conditions in the particle preparation method under Part II, Item 3 were adjusted according to Table 7, the amount of filler was adjusted to 30%, the mass ratio of β-CD to maltodextrin in the filler was adjusted to 2:1, and the basic indicators were measured after preparing coix seed granules. The results are shown in Table 7 (n=3).

[0065] Table 7

[0066] As shown in Table 7, when the roller speed increases, the particle forming rate gradually decreases and the friability gradually increases. When the roller speed increases to 6.8rpm, the particle friability reaches 48.88%, indicating that the particles are easily broken during transportation and storage, and too much fine powder is produced. The main reason is that as the roller speed increases, the material is pressed between the rollers for a shorter time, the plastic deformation or insufficient crushing of the powder particles leads to poor strip hardness and loose particle structure. Therefore, when dry granulating, an appropriate roller speed should be selected to press the strips.

[0067] 3. Optimization of formula granules prescription and preparation process (1) Orthogonal test According to the results of single factor investigation, filler dosage (A), roller pressure (B), and roller speed (C) were selected as the investigation factors, and L93 was selected 4 The test was designed with agglomeration strength, particle forming rate and friability as comprehensive scoring evaluation indicators, and the weights of each indicator were 0.3, 0.4 and 0.3 respectively.

[0068] Comprehensive score = (test value of extract powder agglomeration strength after adding filler / maximum value of extract powder agglomeration strength after adding filler within the group) × 0.3 + (test value of particle forming rate / maximum value of particle forming rate within the group) × 0.4 - (test value of particle friability / maximum value of particle friability within the group) × 0.3.

[0069] Among them, the orthogonal test factor levels are shown in Table 8, and the test results and data statistical analysis are shown in Tables 9 and 10.

[0070] Table 8 Orthogonal test factor level table

[0071] Table 9 Orthogonal test results

[0072] Note: D is blank.

[0073] Table 10 Analysis of variance of test results

[0074] Note: D is blank.

[0075] From the orthogonal test results in Table 9, it is known that the order of influence of the three factors is: filler dosage (A) > roller pressure (B) > roller speed (C). The variance analysis in Table 10 shows that factors A and B have a significant effect on the granulation process (P < 0.05). Considering the volatility of the properties of coix seed extract and production efficiency, the best process is determined to be A3B3C2, A3B2C1 or A2B3C1, that is, the filler dosage is 30~40%, the roller pressure is 80~100bar, and the roller speed is 2.8-3.8rpm. The best process is A3B3C2, that is, the filler dosage is 40%, the roller pressure is 100bar, and the roller speed is 3.8rpm.

[0076] (2) Orthogonal validation test Three verification tests were carried out according to the optimal process conditions determined by the above orthogonal experiment, and the results are shown in Table 11.

[0077] Table 11 Orthogonal validation test results

[0078] As can be seen from Table 11, the granules have a high forming rate and moderate hardness. The indicators of the three batches of samples have little difference. It is found that when the embryo sheets are pressed, there is no sticking to the wheel, the embryo sheets are output continuously and completely, and the color of the granules is uniform, indicating that the granulation process is stable and feasible.

[0079] 3. Cost Analysis According to price inquiries from multiple channels (various auxiliary material companies, Taobao shopping, JD.com, etc.), the market price of β-cyclodextrin is 15.5~17.8 yuan / catty (the average unit price is 16.65 yuan / catty), and the market price of maltodextrin is 6.3~9.5 yuan / catty (the price of maltodextrin DE5-15 is about 7.5~9.5 yuan / catty, with an average unit price of 8.5 yuan / catty). This study started with the addition of 50% β-cyclodextrin to make the formula granules, and after the process parameters were optimized, β-cyclodextrin was combined with relatively cheaper maltodextrin (ratio of 5~3:2~1) for granulation. Although the granule forming rate decreased from 91.34% (see Table 2) with the addition of 50% β-cyclodextrin alone to 82.56% (see Table 11) with the addition of two fillers (β-cyclodextrin and maltodextrin, mass ratio of 2:1), the total amount of filler was reduced from 50% to 30%, and part of the β-cyclodextrin was replaced by cheaper maltodextrin, which significantly reduced the production cost. At this time, the filler used to produce every 1000g of coix seed formula granules was reduced from 547g (price 18.22 yuan) to 363g (price 10.12 yuan), the total amount of filler used was reduced by 33.64%, and the filler price was reduced by 44.46%. The reduction of filler and the increase of drug loading not only reduced the production cost, but also reduced the dosage.

[0080] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A dry granulation process for extract powder of Chinese herbal medicine slices containing fatty oil, characterized in that: The following steps are involved: The extract powder of the Chinese herbal medicine slices containing fatty oil is mixed evenly with the filler, and then the evenly mixed powder is pressed into strips by a dry granulator, and then crushed and sieved; The total fatty oil content of the extract powder is 1-200 mg•g -1 , the filler includes cyclodextrin; The process parameters of dry granulation include: filler dosage is 10~80% of the total material mass, roller pressure is 30~200 bar, and roller speed is 2~10rpm.

2. The dry granulation process according to claim 1, characterized in that: The filler includes cyclodextrin and maltodextrin, and the mass ratio of the two is (5~3): (2~1).

3. The dry granulation process according to claim 1, characterized in that: The cyclodextrin is β-cyclodextrin, and the DE value of the maltodextrin is 5-20.

4. The dry granulation process according to claim 2, characterized in that: The mass ratio of cyclodextrin to maltodextrin is (2~4):

1.

5. A method for optimizing the dry granulation process parameters according to any one of claims 2 to 4, characterized in that: The following steps are involved: Firstly, according to the single factor experiment, the key factors for investigation were screened out with the agglomeration strength of the extract powder after adding the filler, the particle forming rate, the particle friability, the particle bulk density, the particle repose angle and the particle solubility as the basic indicators. Then, the experiment was designed based on the key factors for investigation for optimization. The agglomeration strength of the extract powder after adding the filler, the particle forming rate and the particle friability were used as the comprehensive evaluation indicators. Different weights were set for comprehensive scoring to optimize the dry granulation process parameters.

6. The method according to claim 5, characterized in that: The single factors include filler type, mass ratio of cyclodextrin to maltodextrin, mass ratio of extract powder to filler, correlation between agglomeration strength of extract powder and particle index after adding filler, roller pressure and roller speed.

7. The method according to claim 5, characterized in that: The key factors screened out are filler dosage, roller pressure and roller speed.

8. The method according to claim 5, characterized in that: The weights of the comprehensive evaluation indexes are: the agglomeration strength of the extract powder after adding the filler is 0.3, the particle forming rate is 0.4, and the particle friability is 0.

3.

9. The method according to claim 5, characterized in that: The comprehensive score is calculated as follows: Comprehensive score = (test value of extract powder agglomeration strength after adding filler / maximum value of extract powder agglomeration strength after adding filler within the group) × 0.3 + (test value of particle forming rate / maximum value of particle forming rate within the group) × 0.4 - (test value of particle friability / maximum value of particle friability within the group) × 0.

3.

10. The method according to claim 5, characterized in that: The optimized dry granulation process parameters are as follows: the amount of the filler is 30-40% of the total material mass, the roller pressure is 80-100 bar, and the roller speed is 2.8-3.8 rpm.

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