A stable minocycline hydrochloride capsule and a method for preparing the same

Abstract

The application relates to the technical field of pharmaceutical preparations, and particularly discloses a stable 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 filling agent, 0.1-2 parts of a flow aid and 0.1-3 parts of a lubricant; the filling agent is pre-gelatinized starch; the particle size D 90 80 of the minocycline hydrochloride is below 80 microns; and the composition is prepared into the minocycline hydrochloride capsule by a powder direct filling method. Compared with the prior art, the application has the advantages of simple, fast and low-energy-consumption preparation process, low impurity and good quality of the product.

Description

[0001] This invention is a divisional application of 202510253342.2 filed on March 5, 2025. Technical Field

[0002] This invention relates to the field of pharmaceutical formulation technology, and in particular to a stable minocycline hydrochloride capsule and its preparation method. Background Technology

[0003] Minocycline hydrochloride, chemically named [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-benzotetrabenzamide hydrochloride, is a tetracycline broad-spectrum antibiotic. It exerts its antibacterial effect by preventing the binding of aminoacyl-tRNA to the mRNA-ribosome complex in the bacterial protein synthesis system, thereby inhibiting protein synthesis. It exhibits broad-spectrum antibacterial activity against Gram-positive bacteria such as Staphylococcus, hemolytic streptococci, and Streptococcus pneumoniae, as well as Gram-negative bacteria such as Escherichia coli, Klebsiella spp., and Enterobacter spp. It can be used to treat diseases such as acne, epididymitis, urethritis, gonorrhea, syphilis, peritonitis, infectious enteritis, vulvitis, bacterial vaginosis, intrauterine infection, dacryocystitis, stye, otitis media, sinusitis, periodontitis, periapical periodontitis, maxillary sinusitis, anthrax, scrub typhus, and psittacosis.

[0004] Minocycline hydrochloride capsules were first developed by TRIAX PHARMS and launched in 1971. The original imported minocycline hydrochloride capsule product (trade name: Meiman; manufacturer: Hanhui Pharmaceutical Co., Ltd.) uses a micro-pellet loading process. 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 have the disadvantages of being relatively complex, time-consuming, requiring drying processes, and having high energy consumption. In addition, there is a risk of non-uniformity of content due to the large size and good flowability of the particles.

[0005] Chinese invention application CN104606171A discloses a method for preparing minocycline hydrochloride capsules. The method involves first wet granulation using minocycline hydrochloride, fillers, binders, and plasticizers, followed by spheroidization and drying to obtain drug-loaded pellet cores. These cores are then passed through a fluidized bed to form a sustained-release layer and a coating layer, creating coated microspheres. Finally, the coated microspheres are filled into empty capsules to obtain minocycline hydrochloride capsules. Minocycline hydrochloride readily and rapidly transforms into the impurity diminocycline under high temperature and high humidity conditions, requiring strict control of diminocycline's increase during production. However, this method involves both the preparation of the drug-loaded pellet cores and the formation of the sustained-release and coating layers in a fluidized bed environment at high temperatures and in the presence of significant amounts of organic reagents (ethanol, diethyl phthalate), taking several hours. This may lead to an increase in impurities such as diminocycline, affecting product quality. Furthermore, this method is time-consuming, complex, and energy-intensive, hindering large-scale commercial production.

[0006] The literature "Study on Dissolution Characteristics of Minocycline Hydrochloride Capsules under Different Preparation Processes" (China Science and Technology Journal Database, Medicine, 2021, Vol. 07, pp. 00149-00150) discloses a method for preparing minocycline hydrochloride capsules using a direct powder filling process: minocycline hydrochloride, corn starch, and magnesium stearate are mixed, and the mixture is manually filled into capsule shells. This invention shows that this process, using corn starch as the sole filler, is not conducive to the smooth progress of mixing and capsule filling processes, resulting in unstable fill weight and consequently, problems with content uniformity, making it difficult to apply in large-scale commercial production.

[0007] Therefore, it is necessary to develop a process for preparing minocycline hydrochloride capsules so that high-quality minocycline hydrochloride capsules can be produced simply, quickly, and with low energy consumption. Summary of the Invention

[0008] Purpose of the invention: The technical problem to be solved by the present invention is to provide a minocycline hydrochloride capsule and its preparation method, which addresses the shortcomings of the prior art.

[0009] To solve the above-mentioned technical problems, the present invention discloses the following technical solution:

[0010] In a first aspect, the present invention discloses a minocycline hydrochloride composition.

[0011] In some embodiments, the composition comprises the following components in parts by weight:

[0012] 108 parts of minocycline hydrochloride

[0013] 142-186 parts of filler

[0014] 0.1-2 parts of gliding agent

[0015] Lubricant 0.1-3 parts

[0016] The filler is pregelatinized starch.

[0017] In some embodiments, the composition comprises the following components in parts by weight:

[0018] 108 parts of minocycline hydrochloride

[0019] 152-176 parts of filler

[0020] 0.3-1.8 parts of gliding agent

[0021] Lubricant 0.3-2.8 parts.

[0022] In some embodiments, the composition comprises the following components in parts by weight:

[0023] 108 parts of minocycline hydrochloride

[0024] 162-166 parts of filler

[0025] 0.5-1.6 parts of gliding agent

[0026] Lubricant 0.5-2.6 parts.

[0027] In some embodiments, the particle size D of the minocycline hydrochloride 90 It is below 80μm.

[0028] In some embodiments, the pregelatinized starch with a particle size of 150 μm or less accounts for more than 90% of its total mass, and the pregelatinized starch with a particle size of 425 μm or more accounts for less than 0.5% of its total mass.

[0029] In some embodiments, the flow aid is colloidal silica and / or talc.

[0030] In some embodiments, the lubricant is selected from magnesium stearate, calcium stearate, zinc stearate, sodium fumarate stearate, or any combination thereof.

[0031] Secondly, this invention discloses a minocycline hydrochloride capsule.

[0032] In some embodiments, the minocycline hydrochloride capsule is made from the composition described in the first aspect above; in some embodiments, the capsule further includes one gelatin empty capsule.

[0033] In some embodiments, the method for preparing minocycline hydrochloride capsules from the composition is a direct powder filling method; in some embodiments, the method for preparing minocycline hydrochloride capsules from the composition includes the following steps:

[0034] (1) The filler and flow aid are sieved together to obtain a mixture;

[0035] (2) The resulting mixture was mixed with minocycline hydrochloride to obtain the first total powder;

[0036] (3) Mix the first general-purpose powder and the lubricant together to obtain the second general-purpose powder;

[0037] (4) The second total powder was filled into gelatin capsules to obtain minocycline hydrochloride capsules.

[0038] In step (1), the filler and the flow aid are sieved together in the granulator; the rotation speed of the granulator is 500-900 rpm, and the particle size of the sieve in the granulator is 0.6-1.0 mm.

[0039] In step (2), the obtained mixture is mixed with minocycline hydrochloride in a mixer; the mixing speed is 10-20 rpm and the time is 25-35 min; the loading coefficient of the mixer is 45%-70%.

[0040] In step (3), during the total mixing, the mixing speed is 10-20 rpm and the time is 1-7 min; the loading coefficient of the mixer is 45%-70%.

[0041] In step (4), the filling process involves calculating the filling amount based on the minocycline content of the second total mixed powder, filling the total mixed powder into empty capsules, locking them, and controlling the capsule filling amount difference to be ±5%.

[0042] In some embodiments, after filling, the product is packaged using polyvinyl chloride solid pharmaceutical composite rigid sheet and pharmaceutical aluminum foil.

[0043] Secondly, the present invention discloses a method for preparing the minocycline hydrochloride capsules described in the first aspect above.

[0044] In some embodiments, the method for preparing the minocycline hydrochloride capsules includes the following steps:

[0045] (1) The filler and flow aid are sieved together to obtain a mixture;

[0046] (2) The resulting mixture was mixed with minocycline hydrochloride to obtain the first total powder;

[0047] (3) Mix the first general-purpose powder and the lubricant together to obtain the second general-purpose powder;

[0048] (4) The second total powder was filled into gelatin capsules to obtain minocycline hydrochloride capsules.

[0049] In step (1), the filler and the flow aid are sieved together in the granulator; the rotation speed of the granulator is 500-900 rpm, such as 700 rpm, and the particle size of the sieve in the granulator is 0.6-1.0 mm, such as 0.8 mm.

[0050] 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 time is 25-35 min, such as 30 min; the loading coefficient of the mixer is 45%-70%.

[0051] In step (3), during the total mixing, the mixing speed is 10-20 rpm, such as 11 rpm, and the time is 1-7 min, such as 5 min; the loading coefficient of the mixer is 45%-70%.

[0052] In step (4), the filling process involves calculating the filling amount based on the minocycline content of the second total mixed powder, filling the total mixed powder into empty capsules, locking them, and controlling the capsule filling amount difference to be ±5%.

[0053] In some embodiments, after filling, the product is packaged using polyvinyl chloride solid pharmaceutical composite rigid sheet and pharmaceutical aluminum foil.

[0054] This invention produces minocycline hydrochloride capsules using the above-described method. The preparation process is simple, rapid, and energy-efficient, resulting in good overall powder flowability, low impurities, and good product quality, with dissolution similar to a reference. The minocycline hydrochloride capsules of this invention exhibit the following release characteristics: in a pH 1.2 hydrochloric acid solution, the cumulative dissolution rate is 15%-19% at 5 minutes, 73%-78% at 10 minutes, 85%-89% at 15 minutes, and 96%-99% at 45 minutes; preferably, in a pH 4.5 sodium acetate-acetic acid buffer solution, the cumulative dissolution rate is 14%-18% at 5 minutes, 84%-88% at 10 minutes, 94%-96% at 15 minutes, and 97%-99% at 45 minutes.

[0055] This invention produces minocycline hydrochloride capsules using the above method. These capsules exhibit lower impurity content and better stability compared to the reference formulation under various conditions, including 0 days, 60°C high temperature, 75% RH high humidity, and light exposure. After being stored at 60°C ± 2°C for 30 days, the total impurity content of the minocycline hydrochloride capsules is below 1.7%, preferably below 1.5%; more preferably, after being stored at 75% RH for 30 days, the total impurity content is below 1.4%, preferably below 1.2%; and more preferably, after being exposed to light at 4500 ± 500 lux / h and 90 Mw / cm² for 15 days, the total impurity content is below 1.4%, preferably below 1.2%.

[0056] Beneficial effects:

[0057] The minocycline hydrochloride capsules provided by this invention comprise the active ingredient minocycline hydrochloride, a filler, a flow aid, a lubricant, and a gelatin empty capsule. This invention pulverizes the active ingredient minocycline hydrochloride and prepares the capsules using a direct powder filling process. Pregelatinized starch is used as the filler, ensuring smooth mixing and capsule filling processes with good mixing uniformity. Furthermore, the addition of colloidal silica as a flow aid further improves material flowability, making the mixing and capsule filling processes even smoother. Compared with existing processes, this invention has the advantages of simple and rapid preparation, low energy consumption, low impurities, excellent stability, and good product quality. Attached Figure Description

[0058] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments, and the advantages of the present invention in the above and / or other aspects will become clearer.

[0059] Figure 1 The dissolution curves of the formulations obtained in Example 1, the reference formulation, and Comparative Examples 1-3 in hydrochloric acid medium at pH 1.2 are shown.

[0060] Figure 2 The dissolution curves of the formulations obtained in Example 1, the reference formulation, and Comparative Examples 1-3 in pH 4.5 medium are shown. Detailed Implementation

[0061] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0062] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0063] The pregelatinized starch described in the following examples is manufactured by Carrefour (model: 2001-NEC). According to the Chinese Pharmacopoeia General Chapter 0982, Method II, at least 90% of the sample amount can pass through a sieve with an inner diameter of 150 μm, and the amount of sample that cannot pass through a sieve with an inner diameter of 425 μm is no more than 0.5%. The corn starch is manufactured by Roquette; the colloidal silica is manufactured by Evonik Operations GmbH; and the magnesium stearate is manufactured by Anhui Shanhe (model: SH-YM-M), with a D50 of 5–30 μm.

[0064] The solid content mentioned in the following examples is a percentage by mass.

[0065] The reference formulation described in this invention is manufactured by Pfizer Japan Inc. and marketed under the brand name Minomycin.

[0066] Example 1

[0067] The preparation method of minocycline hydrochloride capsules, when producing 10,000 capsules, includes the following steps:

[0068] (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0069] 108 parts minocycline hydrochloride, 164 parts pregelatinized starch, 0.5 parts colloidal silica, and 0.5 parts magnesium stearate.

[0070] (2) Pulverization: Minocycline hydrochloride was pulverized to obtain the particle size D of the pulverized raw material. 90 <80μm.

[0071] (3) Co-sieving: The colloidal silica and pregelatinized starch from step (1) are put into a rotary granulator in sequence and sieved together at a speed of 700 rpm using a 0.8 mm sieve to obtain a mixture of colloidal silica and pregelatinized starch.

[0072] (4) Total Mixing: The mixture obtained in step (3) and the pulverized raw material obtained in step (2) are added to the mixer in sequence. The loading coefficient of the mixer is 45%-70%. The mixture is mixed at 11 rpm for 30 minutes to obtain Total Mixing Powder 1.

[0073] (5) Total Mix 2: Add the total mixed powder 1 obtained in step (4) to magnesium stearate and mix at 11 rpm for 5 min to obtain total mixed powder 2. The loading coefficient of the mixer is 45%-70%. Take a sample to test the content of total mixed powder 2 and calculate the loading amount based on the content result.

[0074] (6) Filling: Place the total mixed powder obtained in step (5) into a capsule filling machine and fill it with gelatin empty capsules to obtain minocycline hydrochloride capsules, and control the filling volume difference within ±5%.

[0075] (7) Packaging: The packaging uses polyvinyl chloride solid pharmaceutical composite hard sheet and pharmaceutical aluminum foil.

[0076] Example 2

[0077] Same as Example 1, except that the amounts of each component are different, as detailed below:

[0078] Example 2-1: 108 parts minocycline hydrochloride, 142 parts pregelatinized starch, 0.5 parts colloidal silica, and 0.5 parts magnesium stearate.

[0079] Example 2-2: 108 parts minocycline hydrochloride, 186 parts pregelatinized starch, 0.5 parts colloidal silica, and 0.5 parts magnesium stearate.

[0080] Example 2-3: 108 parts minocycline hydrochloride, 164 parts pregelatinized starch, 0.1 parts colloidal silica, and 3.0 parts magnesium stearate.

[0081] Examples 2-4: 108 parts minocycline hydrochloride, 164 parts pregelatinized starch, 2.0 parts colloidal silica, and 0.1 parts magnesium stearate.

[0082] Example 3

[0083] Same as in Example 1, except that the rotary granulator used for co-screening in step (3) is replaced with a gyratory granulator, as detailed below:

[0084] (3) Co-sieving: The colloidal silica and pregelatinized starch from step (1) are put into the oscillating granulator in sequence and co-sieved using a 0.8mm sieve to obtain a mixture of colloidal silica and pregelatinized starch.

[0085] Comparative Example 1

[0086] The preparation method of minocycline hydrochloride capsules, when producing 10,000 capsules, includes the following steps:

[0087] (1) Weighing and sieving: Weigh each raw material and auxiliary material according to the weight ratio.

[0088] 108 parts minocycline hydrochloride, 164 parts pregelatinized starch, 0.5 parts colloidal silica, and 0.5 parts magnesium stearate.

[0089] (2) Pulverization: Minocycline hydrochloride was pulverized to obtain the particle size D of the pulverized raw material. 90 <80μm.

[0090] (3) Granulation: The pregelatinized starch and minocycline hydrochloride from step (2) are put into a wet granulator. The stirring paddle is turned on and mixed at 500 rpm for 5 minutes. Then, 54 parts of purified water are slowly added as a binder solution and the cutting paddle is turned on (900 rpm) to granulate. The wet granules are obtained by granulating with a 20-mesh screen using a swing granulator. The wet granules are dried in a fluidized bed at a temperature of 30℃~40℃ until the moisture content is less than 2% to obtain dry granules. The dry granules are granulated with a 30-mesh screen using a swing granulator.

[0091] (4) Total Mixing: Manually pass the colloidal silica through a 0.8mm sieve, add the granulated dry particles obtained in step (3) to the sieved colloidal silica and mix in a mixer at 11 rpm for 5 minutes to obtain Total Mixing Powder 1.

[0092] (5) Total Mixture 2: Add the total mixed powder 1 obtained in step (4) to magnesium stearate and mix in a mixer at 11 rpm for 5 minutes to obtain total mixed powder 2. Take a sample to test the content of the total mixed powder and calculate the filling amount based on the content result.

[0093] (6) Filling: The total powder obtained in step (5) is placed in a capsule filling machine and filled with gelatin empty capsules to obtain minocycline hydrochloride capsules, and the filling volume difference is controlled within ±5%.

[0094] (7) Packaging: The packaging uses polyvinyl chloride solid pharmaceutical composite hard sheet and pharmaceutical aluminum foil.

[0095] Comparative Example 2

[0096] Same as Example 1, except that the particle size of the raw material after pulverization is D. 90 The size ranges from 90μm to 120μm.

[0097] Comparative Example 3

[0098] Same as Example 1, except that 164 parts of pregelatinized starch are replaced with 164 parts of corn starch.

[0099] Experiment 1

[0100] Dissolution was measured using a Chinese Pharmacopoeia dissolution apparatus 2 at 37°C in a 900 ml solution of hydrochloric acid (pH 1.2) and sodium acetate-acetic acid buffer (pH 4.5). Ultraviolet spectrophotometry was used to determine the dissolution rate at 348 nm. The experimental results are shown in Table 1 and [Table data missing]. Figure 1-2 As shown, the dissolution rates of the embodiments and comparative examples of the present invention are all qualified (cumulative dissolution rate greater than 80% at 45 minutes). The dissolution curve of Example 1 is similar to that of the reference preparation. Comparative Example 1, which uses a wet granulation process, and Comparative Example 3, which uses corn starch as a filler, dissolve slightly slower in a pH 4.5 medium. Comparative Examples 1-3 dissolve faster in a pH 1.2 hydrochloric acid solution at 5 minutes. Comparative Examples 1-2 also dissolve faster in a pH 4.5 sodium acetate-acetic acid buffer solution.

[0101] Table 1. Dissolution rates (%) of the formulations obtained in Example 1, Reference Formulation, and Comparative Examples 1-3 in different media.

[0102]

[0103] Experiment 2

[0104] The formulations obtained in Example 1, the reference formulation, and the formulations obtained in Comparative Examples 1 and 3 were simultaneously subjected to the influence of factors (high temperature 60°C, high humidity RH 75%, light intensity 4500±500 lux / h, 90 Mw / cm²). 2The study included a placement (naked) environment for comparison of properties, related substances, and content. The method for detecting related substances was area normalization. The liquid chromatography method used was the Chinese Pharmacopoeia 2020 edition: octylsilane-bonded silica gel was used as the packing material; the mobile phase was 0.2 mol / L ammonium acetate-dimethylformamide-tetrahydrofuran (600:398:2, containing 0.01 mol / L disodium ethylenediaminetetraacetate); the detection wavelength was 280 nm; and the injection volume was 10 μl. For the test solution, an appropriate amount of the product was dissolved in water and diluted to prepare a solution containing approximately 0.5 mg per ml. Results: The products of Example 1, the reference preparation, and Comparative Example 1 showed similar properties at each time point, with contents ranging from yellow to dark yellow powder or granules. At day 0 and day 30, the related substances in Example 1 were significantly better than those in the reference preparation and the preparations obtained in Comparative Examples 1 and 3, as shown in Table 2 below.

[0105] Table 2

[0106]

[0107] According to Experiment 2, other examples and comparative examples were tested, and 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, which used a swing granulator instead of a rotary granulator for co-sieving, and Comparative Example 2, which increased the particle size of the active pharmaceutical ingredient, were not significantly affected. The impurities in Comparative Example 3, which used corn starch as a filler, were significantly higher than those in Example 1.

[0108] Table 3 Impurity content (%) for each group

[0109]

[0110] Experiment 3

[0111] The angles of repose of Examples 1, 3, and 3 were measured. The angles of repose of Examples 1, 3, and 3 were 35°, 36°, and 56°, respectively. The powder flowability of Examples 1 and 3 was much better than that of Comparative Example 3.

[0112] Meanwhile, the content uniformity of the products of Example 1, Example 3 and Comparative Example 3 was determined, and 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 determined, and the experimental results show that the RSD of the samples of Example 2 and Comparative Example 2 is 0.9%-1.5%, and the content uniformity meets the requirements.

[0113] Table 4. Content uniformity of each group (%)

[0114] 1 96.2 99.5 96.3 2 97.7 96.8 101.2 3 98 98.5 107.1 4 96.7 98 91.3 5 96.6 97.8 99.7 6 96.8 98.3 97.4 7 97.9 98 92.1 8 97 97.8 105.5 9 95.1 95.8 90.4 10 97.4 96.2 94.1 X bar 96.94 97.67 97.51 RSD 0.91％ 1.14％ 5.98％

[0115] Experiment 4: Equivalence test between the formulation obtained in Example 1 and the reference formulation

[0116] In the bioequivalence study between the formulation obtained in Example 1 and the reference formulation, the experimental design was two formulations, two cycles, and crossover single fasting administration. Through data statistics, confidence intervals were calculated. If the interval is within the range of 80-125%, it can be considered that the formulation obtained in Example 1 and the reference formulation are equivalent (see "Technical Guidelines for Human Bioequivalence Studies of Generic Chemical Drugs with Pharmacokinetic Parameters as Endpoint Evaluation Indicators").

[0117] Table 5. BE (Bioequivalence) data (fasting): Statistical analysis results of minocycline hydrochloride capsules (fasting, N=8)

[0118]

[0119] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A minocycline hydrochloride capsule, characterized in that, The following composition is prepared by direct powder filling; the composition comprises the following components in parts by weight: 108 parts of minocycline hydrochloride 142-186 parts of filler 0.1-2 parts of gliding agent Lubricant 0.1-3 parts The filler is pregelatinized starch; The flow aid is colloidal silica; The lubricant is selected from magnesium stearate. The particle size D of the minocycline hydrochloride 90 Below 80μm; The minocycline hydrochloride capsules have the following release characteristics: in a pH 1.2 hydrochloric acid solution, the cumulative dissolution rate is 15%-19% at 5 minutes, 73%-78% at 10 minutes, 85%-89% at 15 minutes, and 96%-99% at 45 minutes; The total impurity content of the minocycline hydrochloride capsules after being stored at 60℃±2℃ for 30 days is less than 1.7%; and / or, the total impurity content of the minocycline hydrochloride capsules after being stored at RH 75% for 30 days is less than 1.4%; and / or, the total impurity content of the minocycline hydrochloride capsules after being stored at 4500±500 lux / h and 90 Mw / cm 2 After 15 days of light exposure, the total impurity content was below 1.4%.

2. The minocycline hydrochloride capsules according to claim 1, characterized in that, The weight parts of each component in the composition are as follows: 108 parts of minocycline hydrochloride 152-176 parts of filler 0.3-1.8 parts of gliding agent Lubricant 0.3-2.8 parts.

3. The minocycline hydrochloride capsules according to claim 1, characterized in that, The weight parts of each component in the composition are as follows: 108 parts of minocycline hydrochloride 162-166 parts of filler 0.5-1.6 parts of gliding agent Lubricant 0.5-2.6 parts.

4. The minocycline hydrochloride capsules according to claim 1, 2, or 3, characterized in that, The powder direct filling method includes the following mixing steps: (1) The filler and the gliding agent are sieved together to obtain a mixture; (2) The resulting mixture was mixed with minocycline hydrochloride to obtain the first total powder; (3) The first general powder is mixed with the lubricant to obtain the second general powder.

5. The minocycline hydrochloride capsules according to claim 4, 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 sieve 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 and the time is 25-35 min; the loading coefficient of the mixer is 45%-70%; in step (3), during the total mixing, the mixing speed is 10-20 rpm and the time is 1-7 min; the loading coefficient of the mixer is 45%-70%.

6. The minocycline hydrochloride capsules according to claim 4, characterized in that, The method of preparing minocycline hydrochloride capsules from the composition further includes filling; filling gelatin empty capsules with the second total mixture powder.

7. The method for preparing minocycline hydrochloride capsules according to claim 1, 2, or 3, characterized in that, The method includes the following mixing steps: (1) The filler and the gliding agent are sieved together to obtain a mixture; (2) The resulting mixture was mixed with minocycline hydrochloride to obtain the first total powder; (3) The first general powder is mixed with the lubricant to obtain the second general powder.

8. The preparation method according to claim 7, 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 sieve 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 and the time is 25-35 min; the loading coefficient of the mixer is 45%-70%; in step (3), during the total mixing, the mixing speed is 10-20 rpm and the time is 1-7 min; the loading coefficient of the mixer is 45%-70%.

9. The preparation method according to claim 7, characterized in that, The method of preparing minocycline hydrochloride capsules from the composition further includes filling; filling gelatin empty capsules with the second total mixture powder.

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