Minocycline hydrochloride capsule and preparation method thereof

Abstract

The present invention relates to the technical field of pharmaceutical preparations, and specifically discloses a minocycline hydrochloride capsule and a preparation method thereof, wherein the minocycline hydrochloride capsule is prepared from a composition comprising 108 parts of minocycline hydrochloride, 142-186 parts of a filler, 0.1-2 parts of a glidant, and 0.1-3 parts of a lubricant. Compared with the existing process, the present invention has the advantages of simple, fast, low energy consumption, low product impurities, and good quality.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a stable minocycline hydrochloride capsule and a preparation method thereof. Background Art

[0002] Minocycline hydrochloride, with the chemical name [4S-(4a, 4aa, 5aa, 12aa)]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide hydrochloride, is a tetracycline-type broad-spectrum antibiotic that exerts its antibacterial effect by preventing aminoacyl t-RNA from binding to the m-RNA ribosome complex in the bacterial protein synthesis system, thereby preventing protein synthesis. It has broad-spectrum antibacterial activity against Gram-positive bacteria such as Staphylococcus, hemolytic Streptococcus and Streptococcus pneumoniae, as well as Gram-negative bacteria such as Escherichia coli, Klebsiella and Enterobacter. It can be used to treat acne, epididymitis, urethritis, gonococcal infection, syphilis, peritonitis, infectious enteritis, vulvitis, bacterial vaginitis, intrauterine infection, dacryocystitis, sty, otitis media, sinusitis, periodontitis, apical periodontitis, palatine sinusitis, anthrax, scrub typhus, psittacosis and other diseases.

[0003] Minocycline hydrochloride capsules were first developed by TRIAX PHARMS and launched on the market in 1971. The original imported minocycline hydrochloride capsules (trade name: Meiman; manufacturer: Hanhui Pharmaceutical Co., Ltd.) are micro-pellet drug application processes. The Japanese reference Minomycin produced by Pfizer Japan Inc. contains a large number of minocycline hydrochloride particles and corn starch particles of about 1 mm. Both production processes are relatively complex, time-consuming, require a drying process, and have high energy consumption. There is also a risk of unqualified content uniformity due to excessively large particles and excessive fluidity.

[0004] China's invention application CN104606171A discloses a method for preparing minocycline hydrochloride capsules, firstly using minocycline hydrochloride, filler, adhesive and plasticizer for wet granulation, and obtaining a drug-loaded pill core through spheronization and drying processes, and then forming a double protective layer of a sustained-release layer and a coating layer in a fluidized bed to obtain coated pellets, and finally filling the coated pellets into empty capsules to obtain minocycline hydrochloride capsules. Minocycline hydrochloride is easily and quickly converted into impurity-biased minocycline under high temperature and high humidity conditions, and the increase of impurity-biased minocycline needs to be strictly controlled during the production process. However, this method is completed at a high temperature and in the presence of more organic reagents (ethanol, diethyl phthalate) in this method, whether it is the preparation of the drug-loaded pill core or the formation of the sustained-release layer and the coating layer by the fluidized bed, and the time is as long as several hours, which may lead to the increase of impurity-biased minocycline, etc., affecting the product quality. Moreover, this method takes a long time to produce, has a complex process, and high energy consumption, which is not conducive to large-scale commercial production.

[0005] The document "Study on the Dissolution Characteristics of Minocycline Hydrochloride Capsules with Different Preparation Processes" (China Science and Technology Journal Database Medicine, Issue 07, 2021, 00149-00150) discloses a method for preparing minocycline hydrochloride capsules by a powder direct filling process: minocycline hydrochloride, corn starch, and magnesium stearate are mixed, and the mixed powder is manually filled into the capsule shell. The present invention's research shows that this process uses corn starch as the only filler, which is not conducive to the smooth progress of production processes such as mixing and capsule filling, and the loading amount is unstable, which leads to content uniformity problems, making it difficult to apply in large-scale commercial production.

[0006] Therefore, it is necessary to develop a process for preparing minocycline hydrochloride capsules so as to produce minocycline hydrochloride capsules of good quality in a simple, rapid and low-energy manner. Summary of the invention

[0007] Purpose of the invention: The technical problem to be solved by the present invention is to provide a minocycline hydrochloride capsule and a preparation method thereof in view of the deficiencies in the prior art.

[0008] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0009] In a first aspect, the present invention discloses a minocycline hydrochloride composition.

[0010] In some embodiments, the composition includes the following components in parts by weight:

[0011] Minocycline hydrochloride 108 parts

[0012] Filler 142-186 parts

[0013] Flow aid 0.1-2 parts

[0014] Lubricant 0.1-3 parts

[0015] The filler is pregelatinized starch.

[0016] In some embodiments, the composition includes the following components in parts by weight:

[0017] Minocycline hydrochloride 108 parts

[0018] Filler 152-176 parts

[0019] 0.3-1.8 parts of flow aid

[0020] Lubricant 0.3-2.8 parts.

[0021] In some embodiments, the composition includes the following components in parts by weight:

[0022] Minocycline hydrochloride 108 parts

[0023] Filler 162-166 parts

[0024] 0.5-1.6 parts of flow aid

[0025] Lubricant 0.5-2.6 parts.

[0026] In some embodiments, the particle size D of minocycline hydrochloride is 90 Less than 80μm.

[0027] In some embodiments, the pregelatinized starch has a particle size of less than 150 μm accounting for more than 90% of its total mass, and a particle size of more than 425 μm accounting for less than 0.5% of its total mass.

[0028] In some embodiments, the glidant is colloidal silicon dioxide and / or talc.

[0029] In some embodiments, the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, or a combination of any of the foregoing.

[0030] In a second aspect, the present invention discloses a minocycline hydrochloride capsule.

[0031] In some embodiments, the minocycline hydrochloride capsule is made of the composition of the first aspect described above; in some embodiments, the capsule further comprises a hollow gelatin capsule.

[0032] In some embodiments, the method for preparing the composition into minocycline hydrochloride capsules is a powder direct filling method; in some embodiments, the method for preparing the composition into minocycline hydrochloride capsules comprises the following steps:

[0033] (1) Sieve the filler and the glidant together to obtain a mixture;

[0034] (2) mixing the obtained mixture with minocycline hydrochloride to obtain a first total mixed powder;

[0035] (3) Mixing the first mixed powder and the lubricant to obtain a second mixed powder;

[0036] (4) Filling the second mixed powder into gelatin capsule shells to obtain minocycline hydrochloride capsules.

[0037] In step (1), the filler and the flow aid are sieved together in a granulator; the rotation speed of the granulator is 500-900 rpm, and the particle size of the screen in the granulator is 0.6-1.0 mm.

[0038] In step (2), the obtained mixture is mixed with minocycline hydrochloride in a mixer; the mixing speed is 10-20 rpm, the mixing time is 25-35 min; and the charging factor of the mixer is 45%-70%.

[0039] In step (3), during the total mixing, the mixing speed is 10-20 rpm, and the mixing time is 1-7 min; the charging factor of the mixer is 45%-70%.

[0040] In step (4), the filling is performed by calculating the filling amount according to the minocycline content of the second total mixed powder, filling the second total mixed powder into empty capsules, locking them, and controlling the difference in the capsule filling amount to ±5%.

[0041] In some embodiments, after filling, polyvinyl chloride solid medicinal composite hard tablets and medicinal aluminum foil are used for packaging.

[0042] In a second aspect, the present invention discloses a method for preparing the minocycline hydrochloride capsules described in the first aspect.

[0043] In some embodiments, the preparation method of the minocycline hydrochloride capsules comprises the following steps:

[0044] (1) Sieve the filler and the glidant together to obtain a mixture;

[0045] (2) mixing the obtained mixture with minocycline hydrochloride to obtain a first total mixed powder;

[0046] (3) Mixing the first mixed powder and the lubricant to obtain a second mixed powder;

[0047] (4) Filling the second mixed powder into gelatin capsule shells to obtain minocycline hydrochloride capsules.

[0048] In step (1), the filler and the flow aid are sieved together in a granulator; the rotation speed of the granulator is 500-900 rpm, such as 700 rpm, and the particle size of the screen in the granulator is 0.6-1.0 mm, such as 0.8 mm.

[0049] In step (2), the obtained mixture is mixed with minocycline hydrochloride in a mixer; the mixing speed is 10-20 rpm, such as 11 rpm, and the mixing time is 25-35 min, such as 30 min; and the charging factor of the mixer is 45%-70%.

[0050] In step (3), during the total mixing, the mixing speed is 10-20 rpm, such as 11 rpm, and the mixing time is 1-7 min, such as 5 min; the charging factor of the mixer is 45%-70%.

[0051] In step (4), the filling is performed by calculating the filling amount according to the minocycline content of the second total mixed powder, filling the second total mixed powder into empty capsules, locking them, and controlling the difference in the capsule filling amount to ±5%.

[0052] In some embodiments, after filling, polyvinyl chloride solid medicinal composite hard tablets and medicinal aluminum foil are used for packaging.

[0053] The present invention prepares minocycline hydrochloride capsules by the above method, and the preparation process of the capsules is simple, fast, low in energy consumption, good total mixed powder fluidity, low in product impurities, good quality, and dissolution is similar to the reference. The minocycline hydrochloride capsules of the present invention have the following release characteristics: in a pH 1.2 hydrochloric acid solution, the cumulative dissolution in 5 minutes is 15%-19%, the cumulative dissolution in 10 minutes is 73%-78%, the cumulative dissolution in 15 minutes is 85%-89%, and the cumulative dissolution in 45 minutes is 96%-99%; preferably, in a pH 4.5 sodium acetate-acetic acid buffer, the cumulative dissolution in 5 minutes is 14%-18%, the cumulative dissolution in 10 minutes is 84%-88%, the cumulative dissolution in 15 minutes is 94%-96%, and the cumulative dissolution in 45 minutes is 97%-99%.

[0054] The present invention prepares minocycline hydrochloride capsules by the above method, and the capsules have lower impurity content than the reference preparation under 0 day, 60°C high temperature, RH75% high humidity and illumination conditions, and have good stability. After the minocycline hydrochloride capsules are placed under the conditions of 60°C±2°C for 30 days, the total impurity content is less than 1.7%, preferably less than 1.5%; preferably, after the minocycline hydrochloride capsules are placed under the conditions of RH 75% for 30 days, the total impurity content is less than 1.4%, preferably less than 1.2%; preferably, after the minocycline hydrochloride capsules are illuminated at 4500±500lux / h, 90Μw / cm2 for 15 days, the total impurity content is less than 1.4%, preferably less than 1.2%.

[0055] Beneficial effects:

[0056] The minocycline hydrochloride capsule provided by the present invention comprises an active ingredient, minocycline hydrochloride, a filler, a glidant, a lubricant and a gelatin hollow capsule. The present invention crushes the minocycline hydrochloride active ingredient, prepares the minocycline hydrochloride capsule by a powder direct filling process, adopts pregelatinized starch as a filler, can ensure the smooth progress of the mixing and capsule filling process, and has good mixing uniformity. In addition, the glidant colloidal silicon dioxide is added to the prescription to further improve the material fluidity, so that the mixing and capsule filling production process is smoother. Compared with the existing process, the present invention has the advantages of simple preparation process, fast, low energy consumption, low product impurities, excellent stability and good quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0058] Figure 1 The dissolution curves of the preparations obtained in Example 1, the reference preparation and Comparative Examples 1-3 in a pH 1.2 hydrochloric acid medium are shown.

[0059] Figure 2 The dissolution curves of the preparations obtained in Example 1, the reference preparation and Comparative Examples 1-3 in a pH 4.5 medium are shown. DETAILED DESCRIPTION

[0060] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0061] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0062] The manufacturer of the pregelatinized starch described in the following examples is Colorcon (Model: 2001-NEC). According to the second method of the General Chapter 0982 of the Chinese Pharmacopoeia, the amount of the sample that can pass through the sieve with an inner diameter of 150 μm is not less than 90% of the test amount, and the amount of the sample that cannot pass through the sieve with an inner diameter of 425 μm is not more than 0.5%; the manufacturer of corn starch is Roquette; the manufacturer of colloidal silicon dioxide is Evonik Operations GmbH; the manufacturer of magnesium stearate is Anhui Shanhe (Model: SH-YM-M), and D50 is 5-30 μm.

[0063] The solid contents described in the following examples are in mass percentage.

[0064] The reference preparation described in the present invention: manufacturer: Pfizer Japan Inc., trade name: Minomycin.

[0065] Example 1

[0066] The preparation method of minocycline hydrochloride capsules, when producing 10,000 capsules, comprises the following steps:

[0067] (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0068] 108 parts of minocycline hydrochloride, 164 parts of pregelatinized starch, 0.5 parts of colloidal silicon dioxide, and 0.5 parts of magnesium stearate.

[0069] (2) Crushing: crush minocycline hydrochloride to obtain a particle size D of the raw material after crushing. 90 <80μm.

[0070] (3) Co-sieving: The colloidal silicon dioxide and pregelatinized starch prepared in step (1) are sequentially placed into a rotary granulator and co-sifted at a rotation speed of 700 rpm using a 0.8 mm sieve to obtain a mixture of colloidal silicon dioxide and pregelatinized starch.

[0071] (4) Total mixing: The mixture obtained in step (3) and the crushed API obtained in step (2) are added into a mixer in sequence. The mixer has a loading factor of 45% to 70%. The mixture is mixed at a speed of 11 rpm for 30 min to obtain total mixed powder 1.

[0072] (5) Mixing 2: Add magnesium stearate to the mixed powder 1 obtained in step (4) and mix at a speed of 11 rpm for 5 min to obtain mixed powder 2. The charging factor of the mixer is 45%-70%. Samples are taken to test the content of the mixed powder 2, and the loading amount is calculated based on the content result.

[0073] (6) Filling: The mixed powder obtained in step (5) is placed in a capsule filling machine and filled into empty gelatin capsules to obtain minocycline hydrochloride capsules, with the filling amount difference controlled within ±5%.

[0074] (7) Packaging: Use polyvinyl chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0075] Example 2

[0076] Same as Example 1, except that the amounts of each component are different, as follows:

[0077] Example 2-1: 108 parts of minocycline hydrochloride, 142 parts of pregelatinized starch, 0.5 parts of colloidal silicon dioxide, and 0.5 parts of magnesium stearate.

[0078] Example 2-2 108 parts of minocycline hydrochloride, 186 parts of pregelatinized starch, 0.5 parts of colloidal silicon dioxide, and 0.5 parts of magnesium stearate.

[0079] Example 2-3: 108 parts of minocycline hydrochloride, 164 parts of pregelatinized starch, 0.1 parts of colloidal silicon dioxide, and 3.0 parts of magnesium stearate.

[0080] Example 2-4: 108 parts of minocycline hydrochloride, 164 parts of pregelatinized starch, 2.0 parts of colloidal silicon dioxide, and 0.1 parts of magnesium stearate.

[0081] Example 3

[0082] The same as Example 1, except that the rotary granulator used for co-sieving in step (3) is replaced by a swing granulator, as follows:

[0083] (3) Co-sieving: The colloidal silicon dioxide and pregelatinized starch prepared in step (1) are sequentially placed into a swing granulator and co-sifted using a 0.8 mm sieve to obtain a mixture of colloidal silicon dioxide and pregelatinized starch.

[0084] Comparative Example 1

[0085] The preparation method of minocycline hydrochloride capsules, when producing 10,000 capsules, comprises the following steps:

[0086] (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0087] 108 parts of minocycline hydrochloride, 164 parts of pregelatinized starch, 0.5 parts of colloidal silicon dioxide, and 0.5 parts of magnesium stearate.

[0088] (2) Crushing: crush minocycline hydrochloride to obtain a particle size D of the raw material after crushing. 90 <80μm.

[0089] (3) Granulation: The pregelatinized starch and the minocycline hydrochloride prepared in step (2) are placed in a wet granulator, the stirring paddle is turned on and mixed at a speed of 500 rpm for 5 minutes, 54 parts of purified water are slowly added as a binder solution, and the cutting paddle is turned on (900 rpm) for granulation. The wet granules are granulated using a swing granulator with a 20-mesh screen, and the wet granules are dried in a fluidized bed at a temperature of 30° C. to 40° C. until the moisture content is less than 2% to obtain dry granules. The dry granules are granulated using a swing granulator with a 30-mesh screen.

[0090] (4) Total mixing: manually pass the colloidal silicon dioxide through a 0.8 mm sieve, add the granulated dry particles obtained in step (3) to the sieved colloidal silicon dioxide, and mix in a mixer at a speed of 11 rpm for 5 min to obtain total mixed powder 1.

[0091] (5) Mixing 2: Add magnesium stearate to the mixed powder 1 obtained in step (4) and mix at 11 rpm for 5 min in a mixer to obtain mixed powder 2. Take samples to test the content of the mixed powder and calculate the filling amount based on the content result.

[0092] (6) Filling: The total mixed powder obtained in step (5) is placed in a capsule filling machine and filled into empty gelatin capsules to obtain minocycline hydrochloride capsules, with the filling amount difference controlled within ±5%.

[0093] (7) Packaging: Use polyvinyl chloride solid pharmaceutical composite hard tablets and pharmaceutical aluminum foil packaging.

[0094] Comparative Example 2

[0095] Same as Example 1, except that the particle size of the raw material drug after crushing is D 90 90μm~120μm.

[0096] Comparative Example 3

[0097] Same as Example 1, except that 164 parts of pregelatinized starch are replaced by 164 parts of corn starch.

[0098] Test 1

[0099] The dissolution was measured at 37°C using the Chinese Pharmacopoeia dissolution apparatus 2 in a pH 1.2 hydrochloric acid solution medium and a pH 4.5 sodium acetate-acetic acid buffer medium at 900 ml. The ultraviolet spectrophotometry was used to measure at a wavelength of 348 nm. The experimental results are shown in Table 1 and Figure 1-2 As shown, the dissolution rates of the embodiments and comparative examples of the present invention are all qualified (the cumulative dissolution rate in 45 minutes is greater than 80%), the dissolution curve of embodiment 1 is similar to that of the reference preparation, comparative example 1 using the wet granulation process and comparative example 3 using corn starch as a filler dissolve slightly slowly in the pH 4.5 medium, comparative examples 1-3 dissolve faster in a pH 1.2 hydrochloric acid solution for 5 minutes, and comparative examples 1-2 also dissolve faster in a pH 4.5 sodium acetate-acetic acid buffer.

[0100] Table 1 Dissolution of the preparations obtained in Example 1, reference preparation, and comparative examples 1-3 in different media (%)

[0101]

[0102] Test 2

[0103] The preparation obtained in Example 1, the reference preparation, and the preparations obtained in Comparative Examples 1 and 3 were simultaneously subjected to the influencing factors (high temperature 60°C, high humidity RH75%, light (4500±500lux / h, 90MW / cm 2)) Placement (naked) study, comparison of properties, related substances, and content. The detection method for related substances is the area normalization method. The liquid phase method uses the Chinese Pharmacopoeia 2020 version method: octylsilane bonded silica gel as filler; 0.2mol / L ammonium acetate-dimethylformamide-tetrahydrofuran (600:398:2, containing 0.01mol / L disodium ethylenediaminetetraacetate) as the mobile phase; the detection wavelength is 280nm; the injection volume is 10μl.

[0104] Test solution: Take an appropriate amount of the product, dissolve it in water and dilute it to make a solution containing about 0.5 mg per 1 ml.

[0105] Results The properties of the products of Example 1, reference preparation and Comparative Example 1 at each time point were similar, and the contents were all yellow to dark yellow powder or granules. The relevant substances in Example 1 were significantly better than those of the reference preparation and the preparations obtained in Comparative Examples 1 and 3 at 0d and 30d, as shown in Table 2 below.

[0106] Table 2

[0107]

[0108] The other examples and comparative examples were tested according to Test 2. The results are shown in Table 3. The impurities in Examples 2-1, 2-2, 2-3 and 2-4 were not significantly affected. The impurities in Example 3 in which a rocking granulator was used instead of a rotary granulator for co-sieving and in Comparative Example 2 in which the particle size of the raw material drug was increased were not significantly affected. The impurities in Comparative Example 3 in which corn starch was used as a filler were significantly higher than those in Example 1.

[0109] Table 3 Impurity content of each group / (%)

[0110]

[0111] Test 3

[0112] The angles of repose of Example 1, Example 3 and Comparative Example 3 were measured. The angles of repose of Example 1, Example 3 and Comparative Example 3 were 35°, 36° and 56°, respectively. The powder fluidity of Example 1 and Example 3 was much better than that of Comparative Example 3.

[0113] At the same time, the content uniformity of the products of Example 1, Example 3 and Comparative Example 3 was measured. The experimental results are shown in Table 4. The content uniformity of Example 1 and Example 3 is significantly better than that of Comparative Example 3. The content uniformity of Example 2 and Comparative Example 2 was measured. The experimental results showed that the RSD of the measurement results of the samples of Example 2 and Comparative Example 2 was 0.9%-1.5%, and the content uniformity met the requirements.

[0114] Table 4 Content uniformity of each group / (%)

[0115]

[0116] Test 4: Equivalence test of the preparation obtained in Example 1 and the reference preparation

[0117] In the bioequivalence experiment between the preparation obtained in Example 1 and the reference preparation, the test design was two preparations, two cycles, and crossover single fasting administration. The confidence interval was calculated through data statistics. The interval was within the range of 80-125%, which can be regarded as equivalent to the preparation obtained in Example 1 and the reference preparation (see "Technical Guidelines for Human Bioequivalence Studies of Generic Chemical Drugs Using Pharmacokinetic Parameters as Endpoint Evaluation Indicators").

[0118] Table 5 BE fasting data: Statistical analysis results of bioequivalence of minocycline hydrochloride capsules (fasting, N=8)

[0119]

[0120] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A minocycline hydrochloride capsule, characterized in that: Made from the following composition; the composition includes the following components in parts by weight: Minocycline hydrochloride 108 parts Filler 142-186 parts Flow aid 0.1-2 parts Lubricant 0.1-3 parts The filler is pregelatinized starch, the glidant is colloidal silicon dioxide, the lubricant is selected from magnesium stearate, and the particle size of minocycline hydrochloride is 90 Less than 80μm; The method for preparing the minocycline hydrochloride capsules from the composition is a powder direct filling method; the method for preparing the minocycline hydrochloride capsules from the composition comprises the following mixing steps: (1) Sieve the filler and the glidant together to obtain a mixture; (2) mixing the obtained mixture with minocycline hydrochloride to obtain a first total mixed powder; (3) The first mixed powder is mixed with a lubricant to obtain a second mixed powder.

2. The minocycline hydrochloride capsule according to claim 1, characterized in that: The weight parts of each component in the composition are as follows: Minocycline hydrochloride 108 parts Filler 152-176 parts Flow aid 0.3-1.8 parts Lubricant 0.3-2.8 parts.

3. The minocycline hydrochloride capsule according to claim 1, characterized in that: The weight parts of each component in the composition are as follows: Minocycline hydrochloride 108 parts Filler 162-166 parts 0.5-1.6 parts of flow aid Lubricant 0.5-2.6 parts.

4. The minocycline hydrochloride capsule according to claim 1, characterized in that: In step (1), the filler and the flow aid are sieved together in a granulator; the rotation speed of the granulator is 500-900 rpm, and the particle size of the screen in the granulator is 0.6-1.0 mm; In step (2), the obtained mixture is mixed with minocycline hydrochloride in a mixer; the mixing speed is 10-20 rpm, the mixing time is 25-35 min; the charging factor of the mixer is 45%-70%; In step (3), during the total mixing, the mixing speed is 10-20 rpm, and the mixing time is 1-7 min; the charging factor of the mixer is 45%-70%.

5. The minocycline hydrochloride capsule according to claim 1, characterized in that: The method for preparing minocycline hydrochloride capsules from the composition further comprises filling: filling the second total mixed powder into gelatin hollow capsules.

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