CN111920777A - Berberine hydrochloride tablet and preparation method thereof - Google Patents
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Abstract
The invention discloses a berberine hydrochloride tablet and a preparation method thereof. In the berberine hydrochloride tablet, the crystal form of the raw material medicine is a single crystal form of berberine hydrochloride dihydrate, and the water content is 5.38-7.40%. The invention also provides a preparation method of the berberine hydrochloride tablet, the crystal form of the raw material medicine in the berberine hydrochloride tablet prepared by the method is a single crystal form of berberine dihydrate, berberine hydrochloride is not contained, heterogeneity of products in the same batch caused by the berberine hydrochloride is effectively avoided, content reduction of effective components of the products caused by the berberine hydrochloride is avoided, batch difference caused by different crystal forms of the raw material medicine is reduced, better quality control is facilitated, and the application prospect is wide.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to a berberine hydrochloride tablet and a preparation method thereof.
Background
Berberine hydrochloride is an iso-ouabain alkaloid extracted and separated from Chinese medicinal plants such as coptis chinensis, has the structure shown in the following formula I, has the effects of resisting bacteria and diminishing inflammation, and is mainly used for treating diseases such as gastrointestinal infection and bacillary dysentery in clinic. Berberine hydrochloride has been used as an over-the-counter medicine in clinic to treat diarrhea, and modern pharmacological studies have also confirmed that berberine hydrochloride has significant effects of resisting heart failure, resisting arrhythmia, reducing cholesterol, inhibiting vascular smooth muscle proliferation, improving insulin resistance, resisting platelet, resisting inflammation and the like, so berberine hydrochloride has wide and important application prospects in cardiovascular and nervous system diseases, and is increasingly paid attention to.
The common preparation of berberine hydrochloride is berberine hydrochloride tablet, and wet granulation is a common process for preparing berberine hydrochloride tablet. Chinese patent application (CN108853035A) discloses a preparation and prescription process of a berberine hydrochloride tablet preparation, which is prepared by wet granulation of the following raw materials in parts by weight: berberine hydrochloride: 1-15 parts, corn starch: 0.36-36 parts of carboxymethyl starch sodium: 0.06-6 parts, 70% ethanol: 0.25-25 parts, 8% starch slurry: 0.20-20 parts, magnesium stearate: 0.004-0.40 parts of silicon dioxide: 0.004-0.40 portion. The preparation process comprises the following steps: s1) sample extraction: selecting ethanol: 0.25 to 25 portions of pure water and 10 to 20 portions of pure water are evenly stirred for 3 to 5 minutes to prepare 70 percent ethanol solution as wetting agent, 0.20 to 20 portions of 8 percent starch slurry (1.6 to 16 portions of corn starch, hot water slurry flushing) is selected to be prepared, and then the mixture is cooled for 3 hours to be used as adhesive; selecting berberine hydrochloride: 1-15 parts, corn starch: 0.36-36 parts of carboxymethyl starch sodium: 0.06-6 parts; s2) sample mixing granulation: the berberine hydrochloride selected in the S1) is mixed: 1-15 parts, corn starch: 0.36-36 parts of carboxymethyl starch sodium: 0.06-6 parts of the mixture is placed in a high-efficiency wet granulator, the stirring is started for 5 minutes at a low speed, the stirring is started for 5 minutes at a high speed, after 10 minutes of stirring, 0.20-20 parts of adhesive of 8% starch slurry is added, a granulating motor is started, and after 5 minutes, the mixture is discharged in a clean, dry and dust-free stainless steel disc; s3) sample drying treatment: putting the wet granules developed in the S2) into a drying vehicle, putting the drying vehicle into a drying room, controlling the temperature inside the drying room at 60-70 ℃, drying the wet granules in the drying room for 2 hours, turning the wet granules for 1 time every 2 hours, checking that the moisture of the granules is 2-4% after 7 hours, and then taking the granules out of the drying room to carry out 16-mesh granule finishing; s4) mixing the dry granules in S3 and a lubricant (magnesium stearate: 0.004-0.40 parts and silicon dioxide: 0.004-0.40 portion) is added into a mixing stirrer to be mixed and stirred for 10 minutes, the sampling is carried out to measure the content of particles, and finally the tablet forming is carried out to prepare the berberine hydrochloride tablet preparation.
Researches show that the berberine hydrochloride dihydrate and the tetrahydrate are easy to interconvert, the berberine hydrochloride raw drug is completely converted into the tetrahydrate under the wet condition, and the berberine hydrochloride raw drug is converted into the dihydrate from the tetrahydrate to different degrees according to different auxiliary material combinations under the dry condition (the proposal for the definition of the berberine hydrochloride crystal form in the Chinese pharmacopoeia, the research and development technical and scientific society of the fourth national crystal form medicament, the Tanghai Yie and the like). Therefore, the production process of the berberine hydrochloride directly influences the crystal form purity of the obtained berberine hydrochloride tablets.
According to the regulation of berberine hydrochloride tablets in the second part of the 'Chinese pharmacopoeia' 2020 edition, the quality control of the berberine hydrochloride in the tablets is required to be calculated by the berberine hydrochloride dihydrate. At present, no preparation process of berberine hydrochloride tablets with single crystal form of berberine hydrochloride dihydrate is reported. The applicant carries out XRD analysis on the berberine hydrochloride tablets sold in the market, and finds that the berberine hydrochloride tablets are all single crystal forms of the berberine tetrahydrate or mixed crystal forms of the berberine tetrahydrate and the berberine dihydrate, and the berberine hydrochloride tablets are not single crystal forms of the berberine dihydrate.
Because the molecular weight of the berberine hydrochloride dihydrate is lower than that of the berberine hydrochloride tetrahydrate, if the preparation process of the berberine hydrochloride tablet containing the berberine hydrochloride dihydrate in a single crystal form can be researched, the batch difference caused by different crystal forms of raw material medicines can be avoided, the content of effective components in the tablet can be improved, and the application prospect is wide.
Disclosure of Invention
The invention aims to provide a berberine hydrochloride tablet with a crystal form of raw material medicine of a dihydrate berberine hydrochloride single crystal form and a preparation method thereof.
The invention provides a berberine hydrochloride tablet, wherein the crystal form of a raw material medicament is a single crystal form of berberine dihydrate hydrochloride, and the water content is 5.38-7.40%.
Further, the moisture content is 7.16% -7.32%.
Further, the berberine hydrochloride tablet is a plain tablet prepared from the following raw material medicines and auxiliary materials in parts by weight:
the raw material medicaments: 90-110 parts of berberine hydrochloride,
auxiliary materials: 40.0-80.0 parts of diluent, 1.0-3.0 parts of adhesive, 5.0-15.0 parts of disintegrating agent, 1.0-3.0 parts of lubricant and 0.5-1.5 parts of glidant;
or the berberine hydrochloride tablet is a coated tablet prepared from the plain tablet and coating powder, and the weight of the coating powder is 2-5% of the total weight of the plain tablet.
Further, the diluent is water-insoluble diluent, preferably one or two of starch and cellulose, and more preferably one or two of pregelatinized starch and microcrystalline cellulose;
the adhesive is selected from one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose and povidone;
the disintegrant is water-insoluble disintegrant, preferably croscarmellose sodium;
the lubricant is one or more selected from magnesium stearate, pulvis Talci, stearic acid, and glyceryl behenate;
the glidant is silicon dioxide, preferably colloidal silicon dioxide.
Further, the plain tablets are prepared from the following raw material medicines and auxiliary materials in parts by weight: 100 parts of berberine hydrochloride, 20.0-40.0 parts of pregelatinized starch, 20.0-40.0 parts of microcrystalline cellulose, 1.0-3.0 parts of hydroxypropyl cellulose, 5.0-15.0 parts of croscarmellose sodium, 1.0-3.0 parts of magnesium stearate and 0.5-1.5 parts of colloidal silicon dioxide;
preferably, the plain tablets are prepared from the following raw material medicines and auxiliary materials in parts by weight: 100 parts of berberine hydrochloride, 25.0 parts of pregelatinized starch, 25.0 parts of microcrystalline cellulose, 2.0 parts of hydroxypropyl cellulose, 10.0 parts of croscarmellose sodium, 1.5 parts of magnesium stearate and 1.0 part of colloidal silicon dioxide.
The invention also provides a preparation method of the berberine hydrochloride tablet, which comprises the following steps:
(1) premixing: taking berberine hydrochloride, diluent, adhesive and disintegrating agent, sieving, pouring into a wet granulator, and premixing;
(2) and (3) granulating: adding a wetting agent into the system premixed in the step (1), carrying out wet granulation in a wet granulator, and sieving and granulating the obtained granules to obtain wet granules;
(3) and (3) drying: drying the wet granules obtained in the step (2) until the moisture content is 5.38-6.50%, and then sieving and grading;
(4) tabletting: uniformly mixing the granules obtained after sieving and grading in the step (3) with a lubricant and a glidant, and tabletting to obtain plain tablets;
and (4) controlling the environmental humidity of the steps (1) to (4) to be 45-65%.
Further, in the step (1), the berberine hydrochloride is sieved by a 100-mesh sieve, and the diluent, the adhesive and the disintegrant are sieved by a 80-mesh sieve; the wet granulator is a high-efficiency wet granulator; the parameters of the premixing are as follows: the mixing time is 600 seconds, the stirring speed is 150 revolutions per minute, and the cutter speed is 200 revolutions per minute;
and/or, in the step (2), the wetting agent is water, and the dosage of the wetting agent is 25-50% of the total weight of the raw material medicine and the auxiliary material, preferably 44%; the wetting agent is added in an atomization way; the parameters of the wet granulation process are as follows: the stirring speed is 150 revolutions per minute, and the cutter speed is 300 revolutions per minute; the sieving whole grain adopts a 18-mesh screen.
Further, in the step (3), the wet granules are dried to a moisture content of 6.14% -6.37%; and/or, the drying process is carried out in a boiling granulation dryer; and/or, a 18-mesh screen is adopted for sieving and grading.
Further, the method further comprises the following coating process: and (4) preparing coating liquid from the coating powder in a solvent, coating the coating liquid on the surface of the plain tablet obtained after tabletting in the step (4) by using coating equipment, and drying to obtain the tablet.
Further, the solvent is 80% ethanol solution, and the solid content in the coating solution is 8%;
and/or the water content of the berberine hydrochloride tablet obtained after drying is 5.38-7.40%, preferably 7.16-7.32%.
In the invention, the moisture content is obtained by detecting and calculating through the following method:
the detection method comprises the following steps: the instrument comprises the following steps: TGA/DSC 2 LF/1100/155; the method comprises the following steps: TGA/DSC, 40-350 deg.C, 10 deg.C/min, Al40ul dt1.00s, 10.00K/min, N2 50.0ml/min。
And (3) calculating: and calculating the mass content of the bound water within an integration range of 70-160 ℃.
In the invention, anhydrous berberine hydrochloride is berberine hydrochloride anhydrous hydrate, dihydrate berberine hydrochloride is berberine hydrochloride dihydrate, and tetrahydrate berberine hydrochloride is berberine hydrochloride tetrahydrate.
Experimental results show that the crystal form of the raw material medicine in the berberine hydrochloride tablet prepared by the method is a single crystal form of berberine hydrochloride dihydrate, does not contain berberine hydrochloride tetrahydrate, accords with the regulation of the berberine hydrochloride tablet in the second part of China pharmacopoeia 2020 edition, and is more favorable for quality control. Moreover, only by adopting the specific preparation process (particularly, controlling the specific moisture content in the final product of the berberine hydrochloride tablet by matching with the specific moisture content of the particles after boiling and drying in the step (7)), the crystal form of the raw material medicine in the prepared berberine hydrochloride tablet is the single crystal form of the berberine dihydrate hydrochloride.
The berberine hydrochloride tablet prepared by the method effectively avoids the nonuniformity of products in the same batch caused by containing the berberine tetrahydrate, avoids the reduction of the content of effective components of the products caused by containing the berberine tetrahydrate, reduces the batch difference caused by different crystal forms of the raw material medicines and has wide application prospect. Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 is a schematic view of the preparation process of berberine hydrochloride tablets of the present invention.
FIG. 2 is an XRD pattern of berberine hydrochloride anhydrous, berberine hydrochloride dihydrate and berberine hydrochloride tetrahydrate.
FIG. 3 is DSC spectra of berberine hydrochloride anhydrous, berberine hydrochloride dihydrate and berberine hydrochloride tetrahydrate.
FIG. 4 is an XRD pattern of a commercially available berberine hydrochloride tablet (manufacturer A, B, C, D) with berberine hydrochloride dihydrate and berberine tetrahydrate as controls.
FIG. 5 is an XRD pattern of berberine hydrochloride tablets of batches 01-03 of the invention, taking berberine hydrochloride dihydrate and berberine hydrochloride tetrahydrate as a contrast.
FIG. 6 shows a DSC chart of a commercially available berberine hydrochloride tablet (manufacturer A, B, C, D).
FIG. 7 is a DSC chart of berberine hydrochloride tablets of batches 01-03 of the present invention.
FIG. 8 is an XRD pattern of a control berberine hydrochloride tablet of Experimental example 2, with berberine hydrochloride anhydrous, berberine hydrochloride dihydrate and berberine hydrochloride tetrahydrate as controls; wherein the control sample 1 is the control berberine hydrochloride tablet 1, the control sample 2 is the control berberine hydrochloride tablet 2, and the control sample 3 is the control berberine hydrochloride tablet 3.
Detailed Description
The raw materials and equipment used in the invention are known products and are obtained by purchasing commercial products.
Example 1 preparation of Berberine hydrochloride tablets of the invention
According to the formula shown in table 1, the berberine hydrochloride tablet of the invention is prepared, the process flow is shown in figure 1, and the environmental humidity in the whole process is controlled to be 45-65%. The method comprises the following specific steps:
(1) sieving: sieving berberine hydrochloride with 100 mesh sieve, and sieving microcrystalline cellulose, pregelatinized starch, hydroxypropyl cellulose, and croscarmellose sodium with 80 mesh sieve.
(2) Pulping: and weighing purified water for later use, wherein the using amount of the purified water is 44 percent of the total weight of the raw and auxiliary materials.
(3) And (3) wet granulation: and pouring the sieved berberine hydrochloride, croscarmellose sodium, pregelatinized starch, hydroxypropyl cellulose and microcrystalline cellulose into an SMG-150 efficient wet granulator in sequence, and covering the machine cover tightly.
(4) Premixing: setting the premixing time to be 600 seconds, the stirring speed to be 150 revolutions per minute and the cutter speed to be 200 revolutions per minute; starting mixing to mix the materials evenly.
(5) And (3) granulating: and (3) setting the stirring speed of the SMG-150 high-efficiency wet granulator to be 150 revolutions per minute and the cutter speed to be 300 revolutions per minute, and atomizing by using an atomizing tank and adding purified water to carry out wet granulation.
(6) Straightening: and (3) using a YK-160 oscillating granulator, and preparing the granules obtained after the wet granulation in the step (5) into wet granules by using an 18-mesh screen.
(7) Boiling and drying: sucking the prepared wet granules into a container of a DPL300 type boiling granulation dryer, drying until the water content of the granules is 6.5%, and collecting.
(8) Straightening: and finishing the granules by using a 18-mesh screen.
(9) Uniformly mixing: the granulated granules were loaded into a YGH-800 two-dimensional motion mixer, colloidal silicon dioxide and magnesium stearate were added, and mixing was started for 15 minutes. After mixing, the granules are put into a double-layer plastic bag, the bag opening is bent, layered and bundled once, the double-layer plastic bag is put into a turnover container, transferred to an intermediate station, weighed and the weight of the granules is recorded.
(10) Preparation before tabletting: the tablet carries out preparation work before production according to the regulations, the moulds with corresponding specifications are taken from the moulds, the procedures are carried out, the punching dies are rechecked and installed, the specifications of the punching dies are consistent with the requirements (phi 8.0mm flat punching without characters), and the phenomena of rolling, unfilled corners, explosion punching, abrasion and the like are avoided.
(11) Tabletting: adding the particles into a hopper, adjusting the height of the hopper to enable the particles to flow smoothly, rotating a hand wheel by hand to enable the upper and lower rails to run for 1-2 weeks without resistance, and then starting operation. And regulating the weight and the pressure of the tablets according to the sequence of regulating the weight of the tablets and then regulating the hardness, checking that the weight, the friability and the surface condition of the tablets meet the quality requirement, and then formally tabletting.
(12) Preparing before coating: preparing a coating solution with solid content of 8 percent: weighing coating powder accounting for 3 percent of the total weight of the plain tablets, pouring the coating powder into 80 percent ethanol solution, and stirring for more than 45 minutes.
(13) Coating: setting the air inlet temperature at 60 ℃, setting the rotating speed of a host at 6rpm and the rotating speed of a peristaltic pump at 50rpm, and coating. Drying was started after the end of the spraying, moisture was measured every 10 minutes after the start of drying (rapid moisture meter) and the temperature was recorded, drying was carried out until the moisture of the coated tablets was 7.40%, and then cooling by ventilation for 10-15 minutes. The berberine hydrochloride tablets of the invention are obtained.
TABLE 1 prescription of berberine hydrochloride tablets of the invention
The beneficial effects of the berberine hydrochloride tablets prepared by the invention are proved by the following experimental examples.
Experimental example 1 XRD test of berberine hydrochloride tablets of the invention
1. Test object
According to the preparation method of example 1, the water content of the granules after drying in step (7) and the water content of the coated tablets after drying in step (13) are controlled according to the following table 2, so that the batches of berberine hydrochloride 01-03 of the invention are prepared:
TABLE 2 moisture content control of Berberine hydrochloride tablets of batches 01-03 of the invention
Commercially available berberine hydrochloride tablets from 4 different manufacturers: manufacturer A, B, C, D.
In the invention, the moisture content is obtained by detecting and calculating through the following method:
the detection method comprises the following steps: the instrument comprises the following steps: TGA/DSC 2 LF/1100/155; the method comprises the following steps: TGA/DSC, 40-350 deg.C, 10 deg.C/min, Al40ul dt1.00s, 10.00K/min, N2 50.0ml/min。
And (3) calculating: and calculating the mass content of the bound water within an integration range of 70-160 ℃.
2. The experimental method comprises the following steps:
taking 01-03 batches of berberine hydrochloride tablets prepared by the method and commercially available berberine hydrochloride tablets, and carrying out X-ray diffraction (XRD) test and Differential Scanning Calorimetry (DSC) test, wherein berberine hydrochloride tetrahydrate and berberine hydrochloride dihydrate are used as reference.
XRD test: 40kV/40mA, a scanning range of 4.0-60 deg, a sampling width of 0.0200deg, a scanning speed of 60deg/min, and continuous scanning.
DSC test: the weight of the sample is 2-4 mg, and the temperature rise speed is 10.00 ℃/min.
3. Results of the experiment
The XRD test result and DSC test result of the commercially available berberine hydrochloride tablet are shown in figure 4 and figure 6 respectively. XRD test results of the prepared 01-03 batches of berberine hydrochloride tablets are shown in figure 5, and DSC test results are shown in figure 7. The characteristic peaks of XRD and the analysis results of the crystal form composition of the raw material medicines are shown in Table 3.
TABLE 3 XRD characteristic peaks and crystal form compositions of commercial products (manufacturers A-D), inventive self-products (batches 01-03), and control samples (controls 1-3)
In Table 3, "NA" indicates that no peak was present.
It can be seen that in the commercially available berberine hydrochloride tablets, the crystal form of the raw material medicine of the manufacturer A is a single crystal form of berberine tetrahydrate, and the crystal form of the raw material medicine of the manufacturer B, C, D is a mixed crystal form of berberine tetrahydrate and berberine dihydrate. In the berberine hydrochloride tablets prepared by the invention, the crystal forms of 01-03 batches of raw material medicines are all single crystal forms of berberine dihydrate and do not contain berberine tetrahydrate.
Therefore, the crystal form of the raw material medicine in the berberine hydrochloride tablet prepared by the process is a single crystal form of berberine hydrochloride dihydrate, and the berberine hydrochloride tablet does not contain the berberine hydrochloride tetrahydrate, so that the heterogeneity of products in the same batch caused by the berberine hydrochloride tetrahydrate is effectively avoided, the content reduction of the effective components of the products caused by the berberine hydrochloride tetrahydrate is avoided, and the batch difference caused by the different crystal forms of the raw material medicine is reduced.
Experimental example 2 screening experiment of Wet granulation Process
1. Test object
The berberine hydrochloride tablets of batches 01 to 03 prepared in the experimental example 1;
referring to the preparation method of example 1, controlling the moisture content of the granules after boiling and drying in step (7) to be 7.00%, and preparing a control berberine hydrochloride tablet 1 in the same manner as in example 1, wherein the moisture content of the control berberine hydrochloride tablet 1 is 9.78%;
referring to the preparation method of example 1, controlling the moisture content of the granules after boiling and drying in step (7) to be 5.00%, and preparing a control berberine hydrochloride tablet 2 in the same manner as in example 1, wherein the moisture content of the control berberine hydrochloride tablet 2 is 7.42%;
referring to the preparation method of example 1, the moisture content of the granules after boiling and drying in step (7) was controlled to be 2.00%, and the rest of the steps were performed in the same manner as in example 1 to obtain control berberine hydrochloride tablets 3, and the moisture content of the obtained control berberine hydrochloride tablets 3 was 4.76%.
In the invention, the moisture content is obtained by detecting and calculating through the following method:
the detection method comprises the following steps: the instrument comprises the following steps: TGA/DSC 2 LF/1100/155; the method comprises the following steps: TGA/DSC, 40-350 deg.C, 10 deg.C/min, Al40ul dt1.00s, 10.00K/min, N2 50.0ml/min。
And (3) calculating: and calculating the mass content of the bound water within an integration range of 70-160 ℃.
2. The experimental method comprises the following steps:
taking the 01-03 batches of berberine hydrochloride tablets, the contrast berberine hydrochloride tablets 1, the contrast berberine hydrochloride tablets 2 and the contrast berberine hydrochloride tablets 3 to perform XRD test, and taking anhydrous berberine hydrochloride, berberine tetrahydrate and berberine dihydrate as contrast. XRD test conditions were the same as in Experimental example 1.
3. Results of the experiment
The XRD test result of the contrast berberine hydrochloride tablets 1-3 is shown in figure 8, and the XRD test result of the 01-03 batches of berberine hydrochloride tablets prepared by the invention is shown in figure 5. The characteristic peaks of XRD and the analysis results of the crystal form composition of the raw material medicines are shown in Table 3.
It can be seen that, in the control berberine hydrochloride tablets 1-3, the crystal form of the raw material drug of the control berberine hydrochloride tablet 1 is the mixed crystal form of the berberine tetrahydrate and the berberine dihydrate, and the crystal forms of the raw material drug of the control berberine hydrochloride tablets 2 and 3 are the mixed crystal form of the berberine dihydrate and the berberine anhydrous. In the berberine hydrochloride tablets prepared by the invention, the crystal forms of 01-03 batches of raw material medicines are all single crystal forms of berberine dihydrate and do not contain berberine tetrahydrate.
Therefore, the crystal form of the raw material medicine in the prepared berberine hydrochloride tablet is the single crystal form of the berberine dihydrate hydrochloride only by adopting the specific preparation process (particularly by matching the specific moisture content of the particles after boiling and drying in the step (7) to control the specific moisture content in the final product of the berberine hydrochloride tablet).
In conclusion, the invention provides a berberine hydrochloride tablet with a crystal form of raw material medicine of a dihydrate berberine hydrochloride single crystal form and a preparation method thereof. The crystal form of the raw material medicine in the berberine hydrochloride tablet prepared by the method is a single crystal form of berberine hydrochloride dihydrate, does not contain berberine hydrochloride tetrahydrate, accords with the regulation of berberine hydrochloride tablets in the second part of China pharmacopoeia 2020 edition, and is more favorable for quality control. In addition, the berberine hydrochloride tablet prepared by the method effectively avoids the nonuniformity of products in the same batch caused by containing the berberine tetrahydrate, avoids the reduction of the content of effective components of the products caused by containing the berberine tetrahydrate, reduces the batch difference caused by different crystal forms of raw material medicines, and has wide application prospect.
Claims (10)
1. A berberine hydrochloride tablet is characterized in that: in the berberine hydrochloride tablet, the crystal form of the raw material medicine is a single crystal form of berberine hydrochloride dihydrate, and the water content is 5.38-7.40%.
2. The berberine hydrochloride tablet of claim 1, wherein: the moisture content is 7.16% -7.32%.
3. The berberine hydrochloride tablet according to claim 1 or 2, wherein: the berberine hydrochloride tablet is a plain tablet prepared from the following raw material medicines and auxiliary materials in parts by weight:
the raw material medicaments: 90-110 parts of berberine hydrochloride,
auxiliary materials: 40.0-80.0 parts of diluent, 1.0-3.0 parts of adhesive, 5.0-15.0 parts of disintegrating agent, 1.0-3.0 parts of lubricant and 0.5-1.5 parts of glidant;
or the berberine hydrochloride tablet is a coated tablet prepared from the plain tablet and coating powder, and the weight of the coating powder is 2-5% of the total weight of the plain tablet.
4. The berberine hydrochloride tablet of claim 3, wherein: the diluent is water-insoluble diluent, preferably is one or two of starch and cellulose, and more preferably is one or two of pregelatinized starch and microcrystalline cellulose;
the adhesive is selected from one or more of hydroxypropyl cellulose, hydroxypropyl methylcellulose and povidone;
the disintegrant is water-insoluble disintegrant, preferably croscarmellose sodium;
the lubricant is one or more selected from magnesium stearate, pulvis Talci, stearic acid, and glyceryl behenate;
the glidant is silicon dioxide, preferably colloidal silicon dioxide.
5. The berberine hydrochloride tablet of claim 4, wherein: the plain tablet is prepared from the following raw material medicines and auxiliary materials in parts by weight: 100 parts of berberine hydrochloride, 20.0-40.0 parts of pregelatinized starch, 20.0-40.0 parts of microcrystalline cellulose, 1.0-3.0 parts of hydroxypropyl cellulose, 5.0-15.0 parts of croscarmellose sodium, 1.0-3.0 parts of magnesium stearate and 0.5-1.5 parts of colloidal silicon dioxide;
preferably, the plain tablets are prepared from the following raw material medicines and auxiliary materials in parts by weight: 100 parts of berberine hydrochloride, 25.0 parts of pregelatinized starch, 25.0 parts of microcrystalline cellulose, 2.0 parts of hydroxypropyl cellulose, 10.0 parts of croscarmellose sodium, 1.5 parts of magnesium stearate and 1.0 part of colloidal silicon dioxide.
6. The method for preparing berberine hydrochloride tablets according to any one of claims 1 to 5, characterized in that: the method comprises the following steps:
(1) premixing: taking berberine hydrochloride, diluent, adhesive and disintegrating agent, sieving, pouring into a wet granulator, and premixing;
(2) and (3) granulating: adding a wetting agent into the system premixed in the step (1), carrying out wet granulation in a wet granulator, and sieving and granulating the obtained granules to obtain wet granules;
(3) and (3) drying: drying the wet granules obtained in the step (2) until the moisture content is 5.38-6.50%, and then sieving and grading;
(4) tabletting: uniformly mixing the granules obtained after sieving and grading in the step (3) with a lubricant and a glidant, and tabletting to obtain plain tablets;
and (4) controlling the environmental humidity of the steps (1) to (4) to be 45-65%.
7. The method of claim 6, wherein: in the step (1), the berberine hydrochloride is sieved by a 100-mesh sieve, and the diluent, the adhesive and the disintegrant are sieved by a 80-mesh sieve; the wet granulator is a high-efficiency wet granulator; the parameters of the premixing are as follows: the mixing time is 600 seconds, the stirring speed is 150 revolutions per minute, and the cutter speed is 200 revolutions per minute;
and/or, in the step (2), the wetting agent is water, and the dosage of the wetting agent is 25-50% of the total weight of the raw material medicine and the auxiliary material, preferably 44%; the wetting agent is added in an atomization way; the parameters of the wet granulation process are as follows: the stirring speed is 150 revolutions per minute, and the cutter speed is 300 revolutions per minute; the sieving whole grain adopts a 18-mesh screen.
8. The method of claim 6, wherein: in the step (3), the wet granules are dried until the moisture content is 6.14% -6.37%; and/or, the drying process is carried out in a boiling granulation dryer; and/or, a 18-mesh screen is adopted for sieving and grading.
9. The method according to any one of claims 6-8, wherein: the method further comprises the following coating process: and (4) preparing coating liquid from the coating powder in a solvent, coating the coating liquid on the surface of the plain tablet obtained after tabletting in the step (4) by using coating equipment, and drying to obtain the tablet.
10. The method of claim 9, wherein: the solvent is 80% ethanol solution, and the solid content in the coating solution is 8%;
and/or the water content of the berberine hydrochloride tablet obtained after drying is 5.38-7.40%, preferably 7.16-7.32%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115477647A (en) * | 2022-10-26 | 2022-12-16 | 山西医科大学 | Berberine fumarate crystal form, preparation method, composition and application thereof |
| CN115572292A (en) * | 2022-10-26 | 2023-01-06 | 山西医科大学 | Berberine succinate crystal form, preparation method, composition and application thereof |
| CN116270516A (en) * | 2023-03-17 | 2023-06-23 | 江苏亚邦爱普森药业有限公司 | Berberine hydrochloride coated tablet and preparation method thereof |
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2020
- 2020-09-18 CN CN202010986571.2A patent/CN111920777A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115477647A (en) * | 2022-10-26 | 2022-12-16 | 山西医科大学 | Berberine fumarate crystal form, preparation method, composition and application thereof |
| CN115572292A (en) * | 2022-10-26 | 2023-01-06 | 山西医科大学 | Berberine succinate crystal form, preparation method, composition and application thereof |
| CN116270516A (en) * | 2023-03-17 | 2023-06-23 | 江苏亚邦爱普森药业有限公司 | Berberine hydrochloride coated tablet and preparation method thereof |
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