Huperzine A capsule and preparation method thereof

Abstract

The invention belongs to the technical field of medicine preparation, and particularly relates to a huperzine A capsule and a preparation method thereof. The huperzine A capsule is prepared from the following components in parts by weight: 0.01 to 0.5 part of huperzine A, 40.0 to 99.0 parts of a filling agent, 0.4 to 4.5 parts of a flow aid and a wetting agent, the filling agent is prepared from an internally added filling agent and an externally added filling agent, the weight part of the flow aid is 10 to 14 percent of the weight part of the internally added filling agent, and the weight part of the wetting agent is 10 to 14 percent of the weight part of the externally added filling agent. Wherein the mesh number of the internally added filler is smaller than that of the externally added filler, and the wetting agent is an ethanol solution. According to the method disclosed by the invention, the filler is used for internal addition and external addition according to the mass ratio of 1: 3, so that the particles have good uniformity and flowability, and the stability of the huperzine-A capsule can be ensured to be better. The huperzine-A capsule prepared by the invention can be quickly dissolved out and released, and is uniform in quality and content.

Description

Technical Field

[0001] The invention belongs to the technical field of drug preparation, and particularly relates to a huperzine A capsule and a preparation method thereof. Background Art

[0002] Alzheimer's disease (AD) is the most common type of dementia, a chronic neurodegenerative disease characterized by progressive memory impairment, cognitive dysfunction, behavioral disorders and personality changes. AD has the characteristics of high morbidity and great harm. It is the largest global public health event facing mankind. Its etiology and pathogenesis are still unclear. In the drug treatment of Alzheimer's disease, there are two main types of drugs that are widely used. The first type is cholinesterase inhibitors. The mechanism of action of this type of drug is to increase the concentration of acetylcholine, a neurotransmitter in the brain. Acetylcholine plays an important role in cognitive function, especially memory and learning. Cholinesterase inhibitors can slow the deterioration of symptoms in patients with mild to moderate Alzheimer's disease and improve their daily living ability. The second type is NMDA receptor antagonists.

[0003] Huperzine A capsules are cholinesterase inhibitors used for benign memory disorders, improving patients' directed memory, associative learning, image recall, meaningless pattern recognition and portrait recall, and also have an improvement effect on memory disorders caused by dementia patients and organic brain lesions; included in the 2020 edition of the "Chinese Pharmacopoeia" Part II, its specification is 50μg, and it belongs to the trace preparations referred to in the Chinese Pharmacopoeia (Part IV) (that is, the labeled amount of each single dose is less than 25mg or the main drug content is less than 25% of the weight of each single dose). The risk of uneven content in the total mixing and capsule filling processes during its production process is relatively high.

[0004] In patent CN116407538A, 0.02%-8% huperzine A and 92%-99.98% mannitol are dissolved in an acidic aqueous solution with a pH of 2-3, mixed and adjusted to pH 3-6, dried and crushed to form a dispersion, and then the dispersion with a mass percentage of 95%-99% is mixed with a mass percentage of 1%-5% mannitol filler. The preparation process is complicated and the introduction of acidic solution has a risk of corrosion to the equipment, but there is no data support such as content uniformity. Patent CN109620810A dissolves huperzine A in 95% ethanol, sprays it into a mixture of diluent and disintegrant, stirs and granulates evenly, dries at 60°C, granulates, adds a lubricant and mixes evenly, and presses into tablets. The weight percentage of huperzine A contained is 0.08%-0.25%; this technical solution solves the problem of increasing related substances, but does not investigate the content uniformity, dissolution curve, and dissolution of the preparation. Summary of the invention

[0005] The purpose of the present invention is to provide a huperzine A capsule and a preparation method thereof.

[0006] The implementation process of the present invention is as follows:

[0007] A huperzine A capsule comprises the following components in parts by weight:

[0008] Huperzine A 0.01-0.5 parts by weight,

[0009] 40.0 to 99.0 parts by weight of filler, wherein the filler is composed of internal filler and external filler,

[0010] 0.4 to 4.5 parts by weight of glidant,

[0011] The weight of the wetting agent is 10% to 14% of the weight of the internal filler;

[0012] Wherein, the mesh number of the internal filler is smaller than the mesh number of the external filler, and the wetting agent is an ethanol solution.

[0013] Furthermore, the mass ratio of the internal filler to the external filler is 1:3.

[0014] Furthermore, the filler is selected from one or more of lactose, microcrystalline cellulose, starch, mannitol, and pregelatinized starch.

[0015] Furthermore, the mesh number of the filler is 80-200 mesh, and the particle sizes corresponding to 80 mesh and 200 mesh are 180 μm and 50 μm respectively.

[0016] Furthermore, the glidant is selected from one or both of silicon dioxide and colloidal silicon dioxide.

[0017] The preparation method of the above-mentioned Huperzine A capsule comprises the following steps:

[0018] S1: co-crushing: the raw material Huperzine A and part of the internal filler are co-crushed to obtain a mixture 1;

[0019] S2: Wet granulation: Transfer mixture 1 and the remaining internal filler to a wet granulator for mixing; start the peristaltic pump, spray the wetting agent into the granulation pot for stirring and granulation, and sieve the soft material to obtain wet granules;

[0020] S3: Drying and granulation: The wet granules are placed in an oven for drying, and after cooling, they are granulated in an oscillating granulator. After granulation, they are spread on a drying tray again, and dried to obtain Huperzine A dry granules;

[0021] S4: Total mixing: The flow aid and the additional filler are premixed separately at a mass ratio of 1:10, sieved, and then mixed with the huperzine A dry granules and the remaining additional filler in a hopper mixer to obtain huperzine A capsule granules, which are then filled to obtain huperzine A capsules.

[0022] Furthermore, in step S2, the atomization pressure of the peristaltic pump is 0.2-0.3 MPa; the rotation speed of the peristaltic pump is 250-350 rpm.

[0023] Furthermore, in step S2, the stirring speed of the granulating pot is 200 rpm, and the cutting speed is 1200 rpm.

[0024] Furthermore, in step S2, the soft material is screened through a mesh size of 12 to 20.

[0025] Furthermore, in step S4, in the hopper mixer, the mixing time is 10 to 20 minutes and the mixing speed is 8 to 12 rpm.

[0026] Positive effects of the present invention:

[0027] (1) In the present invention, the huperzine A raw material and the water-soluble filler are co-pulverized, and the solid form is co-granulated with the internal filler by a wet method. After drying, the granules are further mixed with the external filler, and the product quality stability is good.

[0028] (2) The method of the present invention uses the filler in a mass ratio of 1:3 for internal and external addition processes, so that the particles have good uniformity and fluidity, and can ensure that the content of huperzine A capsules has good uniformity and better batch-to-batch stability.

[0029] (3) The dissolution uniformity data of the huperzine A capsules prepared by the present invention and the dissolution change during the stability study prove that the samples prepared by the present invention can still achieve rapid dissolution and release, uniform quality, and control of content uniformity after removing the disintegrant in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 When the mass ratio of internal filler to external filler is 1:0, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on day 0;

[0031] Figure 2 When the mass ratio of internal filler to external filler is 1:1, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on day 0;

[0032] Figure 3 When the mass ratio of internal filler to external filler is 1:3, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on day 0;

[0033] Figure 4When the mass ratio of internal filler to external filler was 1:5, the HPLC spectrum of the impurities of Huperzine A capsules was tested by sampling on day 0;

[0034] Figure 5 When the mass ratio of internal filler to external filler is 1:0, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on 3 days;

[0035] Figure 6 When the mass ratio of internal filler to external filler is 1:1, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on 3 days;

[0036] Figure 7 When the mass ratio of internal filler to external filler is 1:3, the HPLC spectrum of relevant impurities of Huperzine A capsules was tested by sampling on 3 days;

[0037] Figure 8 When the mass ratio of the internal filler to the external filler was 1:5, samples were taken every 3 days to detect the HPLC spectra of the impurities in the Huperzine A capsules. DETAILED DESCRIPTION

[0038] The present invention will be further described below in conjunction with the embodiments.

[0039] The invention uses huperzine A as an active ingredient, adds a filler (such as lactose, microcrystalline cellulose, starch, mannitol, pregelatinized starch, etc.), adds a flow aid (such as silicon dioxide, colloidal silicon dioxide) to the prescription, and adds an appropriate amount of low-concentration ethanol solution to play the role of adhesive and wetting; through wet granulation, the combination degree of raw materials and auxiliary materials is improved, and after drying, the particles are further mixed with the filler and the flow aid, so that the particles have good fluidity and good content uniformity, thereby ensuring the filling process of the preparation and the content uniformity of the finished product.

[0040] The preparation method of the huperzine A capsule of the present invention comprises the following steps:

[0041] S1: co-crushing: the raw material Huperzine A and part of the internal filler are co-crushed to obtain a mixture 1;

[0042] S2: Wet granulation: Transfer mixture 1 and the remaining internal filler to the wet granulator, mix for 5 minutes until they are evenly mixed; turn on the peristaltic pump, adjust the atomization pressure to 0.2-0.3 MPa, and spray all the wetting agent into the granulation pot at a speed of 300 rpm with the peristaltic pump. Spraying is completed within 3 minutes, stirring speed is 200 rpm, cutting speed is 1200 rpm, and granulation is continued for 2 minutes. The soft material is sieved through a 12-20 mesh sieve to obtain wet granules;

[0043] S3: Drying and granulation: The wet granules were placed in an oven and dried at 60°C, turning the granules every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0044] S4: Total mixing: The flow aid and the additional filler are premixed separately at a mass ratio of 1:10 and passed through a 50-mesh sieve; then, the flow aid and the additional filler are placed in a hopper mixer and mixed for 10 to 20 minutes at a mixing speed of 10 rpm to obtain the huperzine A capsule granules, and the huperzine A capsules are obtained after filling.

[0045] In step S1 of the method of the present invention, the amount of the raw material Huperzine A is small, and it can only be mixed and crushed with a small amount of internal filler in advance to ensure uniform mixing.

[0046] The mixing time of step S2 in the wet granulator in the method of the present invention is not limited. Those skilled in the art set it according to the amount of the mixed material and mix it evenly. The numerical values ​​given in the embodiment are reference values. The atomization pressure and speed of the peristaltic pump are also not limited. Those skilled in the art set it according to experimental needs. The numerical values ​​given in the embodiment are reference values. The wetting agent spraying time is not limited. Those skilled in the art set it according to experimental needs. The numerical values ​​given in the embodiment are reference values. The stirring speed and the cutter speed of the granulating pot are not limited. Those skilled in the art set it according to experimental needs. The numerical values ​​given in the embodiment are reference values.

[0047] The temperature and time of oven drying in step S3 of the method of the present invention are not limited, and those skilled in the art can set them according to experimental needs. In the embodiment of the present invention, it is preferably dried at 60° C., with the material turned over every 45 minutes, and dried for 2 hours.

[0048] The mixing time and mixing speed in the hopper mixer in step S4 of the method of the present invention are not limited, and those skilled in the art can set them according to experimental needs. In the embodiment of the present invention, the mixing time is preferably 10 to 20 minutes and the mixing speed is 10 rpm.

[0049] Example 1

[0050] The prescription of Huperzine A Capsules described in this example is shown in Table 1.

[0051] Table 1 Prescription data of Huperzine A Capsules described in Example 1

[0052]

[0053] The preparation method of Huperzine A capsule described in this embodiment:

[0054] S1: co-crushing: a portion of 200-mesh lactose and 0.01 kg of huperzine A raw material were co-crushed to obtain a mixture 1.

[0055] S2: Wet granulation: Mixture 1 and the remaining 200-mesh lactose are placed in a wet granulator, stirred at 200 rpm, cutter speed at 1200 rpm, and mixed for 5 min until uniform; the peristaltic pump is turned on, the atomization pressure is adjusted to 0.3 MPa, and 1.09 kg of 1% ethanol solution of the wetting agent by volume is sprayed into the granulation pot at a peristaltic pump speed of 300 rpm, and the spraying is completed within 3 min. The stirring speed is 200 rpm, the cutter speed is 1200 rpm, and granulation is continued for 2 min. The soft material is sieved through a 14-mesh sieve to obtain wet granules;

[0056] S3: Drying and granulation: The wet granules were placed in an oven and dried at a temperature below 60°C, with the granules turned over every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0057] S4: Total mixing: 0.4 kg of colloidal silicon dioxide and 100 mesh lactose were premixed separately at a mass ratio of 1:10, and passed through a 50 mesh sieve; then, the mixture was placed in a hopper mixer with huperzine A dry particles and the remaining 100 mesh lactose, and mixed for 15 minutes at a mixing speed of 10 rpm to obtain huperzine A capsule particles, which were then filled to obtain huperzine A capsules. Three batches of samples were prepared in the same manner, and were recorded as: 240101, 240102, and 240103.

[0058] Comparative Example 1 Different ways of adding raw material Huperzine A

[0059] The formula, preparation process and parameters are the same as those in Example 1, except that in step S1, huperzine A is not pulverized together with part of the 200-mesh lactose, but huperzine A is dissolved in ethanol to form a solution, which is then added to the pulverized part of the 200-mesh lactose and mixed. The obtained huperzine A capsule is recorded as FP22070101.

[0060] Comparative Example 2 Different mass ratios of internal fillers and external fillers

[0061] The recipe, preparation process and parameters are the same as those in Example 1, except that the mass ratios of 200 mesh lactose to 100 mesh lactose are 1:0, 1:1 and 1:5, respectively.

[0062] Comparative Example 3 Different mixing times in wet granulation

[0063] The formulation, preparation process and parameters are the same as those in Example 1, except that in the wet granulation of step (S2), the stirring speed is 200 rpm, the cutting speed is 1200 rpm, the mixing time is set to 3 min and 7 min respectively, and the mixing uniformity is tested.

[0064] Example 2

[0065] The prescription of Huperzine A Capsules described in this example is shown in Table 2.

[0066] Table 2 Prescription data of Huperzine A capsules described in Example 2

[0067]

[0068] The preparation method of Huperzine A capsule described in this embodiment:

[0069] S1: co-grinding: a portion of 200-mesh microcrystalline cellulose and 0.5 kg of huperzine A raw material were co-grinded to obtain a mixture 1.

[0070] S2: Wet granulation: Mixture 1 and the remaining 200-mesh microcrystalline cellulose are placed in a wet granulator, stirred at a speed of 200 rpm, and the cutting speed is 1200 rpm, and mixed for 5 minutes until uniform; the peristaltic pump is turned on, and the atomization pressure is adjusted to 0.2 MPa. 3.46 kg of ethanol solution with a volume percentage of wetting agent of 1% is sprayed into the granulation pot at a peristaltic pump speed of 250 rpm. The spraying is completed within 3 minutes. The stirring speed is 200 rpm, the cutting speed is 1200 rpm, and the granulation is continued for 2 minutes. The soft material is passed through a 14-mesh sieve to obtain wet granules;

[0071] S3: Drying and granulation: The wet granules were placed in an oven and dried at a temperature below 60°C, with the granules turned over every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0072] S4: Total mixing: 4.5 kg of colloidal silicon dioxide and additional 100-mesh microcrystalline cellulose are premixed separately at a mass ratio of 1:10 and passed through a 50-mesh sieve; then, the mixture is placed in a hopper mixer with huperzine A dry granules and the remaining 100-mesh microcrystalline cellulose, and mixed for 20 minutes at a mixing speed of 10 rpm to obtain huperzine A capsule granules, and after filling, huperzine A capsules are obtained.

[0073] Example 3

[0074] The prescription of Huperzine A Capsules described in this example is shown in Table 3.

[0075] Table 3 Prescription data of Huperzine A capsule described in Example 3

[0076]

[0077] The preparation method of Huperzine A capsule described in this embodiment:

[0078] S1: co-crushing: a portion of 200-mesh starch and 0.01 kg of huperzine A raw material were co-crushed to obtain a mixture 1.

[0079] S2: Wet granulation: Mixture 1 and the remaining 200-mesh starch are placed in a wet granulator, stirred at a speed of 200 rpm, and the cutting speed is 1200 rpm, and mixed for 5 minutes until uniform; the peristaltic pump is turned on, and the atomization pressure is adjusted to 0.3 MPa. 1 kg of ethanol solution with a volume percentage of wetting agent of 1% is sprayed into the granulation pot at a peristaltic pump speed of 350 rpm, and the spraying is completed within 3 minutes. The stirring speed is 200 rpm, the cutting speed is 1200 rpm, and the granulation is continued for 2 minutes. The soft material is passed through a 12-mesh sieve to obtain wet granules;

[0080] S3: Drying and granulation: The wet granules were placed in an oven and dried at a temperature below 60°C, with the granules turned over every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0081] S4: Total mixing: 0.7 kg of colloidal silicon dioxide and additional 100-mesh microcrystalline cellulose are premixed separately at a mass ratio of 1:10 and passed through a 50-mesh sieve; then, the mixture is placed in a hopper mixer with huperzine A dry particles and the remaining 100-mesh microcrystalline cellulose, and mixed for 15 minutes at a mixing speed of 10 rpm to obtain huperzine A capsule particles, and after filling, huperzine A capsules are obtained.

[0082] Example 4

[0083] The prescription of Huperzine A Capsules described in this example is shown in Table 4.

[0084] Table 4 Prescription data of Huperzine A Capsules described in Example 4

[0085]

[0086] The preparation method of Huperzine A capsule described in this embodiment:

[0087] S1: co-crushing: a portion of 140-mesh mannitol and 0.22 kg of huperzine A raw material were co-crushed to obtain a mixture 1.

[0088] S2: Wet granulation: Mixture 1 and the remaining 140 mesh mannitol are placed in a wet granulator, stirred at a speed of 200 rpm, and the cutting speed is 1200 rpm, and mixed for 5 minutes to mix evenly; the peristaltic pump is turned on, and the atomization pressure is adjusted to 0.3 MPa. 2.97 kg of ethanol solution with a volume percentage of wetting agent of 1% is sprayed into the granulation pot at a speed of 300 rpm of the peristaltic pump. The spraying is completed within 3 minutes. The stirring speed is 200 rpm, the cutting speed is 1200 rpm, and the granulation is continued for 2 minutes. The soft material is passed through a 20-mesh sieve to obtain wet granules;

[0089] S3: Drying and granulation: The wet granules were placed in an oven and dried at a temperature below 60°C, with the granules turned over every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0090] S4: Total mixing: 0.9 kg of colloidal silicon dioxide and additional 100 mesh mannitol are premixed separately at a mass ratio of 1:10 and passed through a 50 mesh sieve; then, the premixed mixture is placed in a hopper mixer with huperzine A dry granules and the remaining 100 mesh mannitol and mixed for 10 minutes at a mixing speed of 8 rpm to obtain huperzine A capsule granules, and the huperzine A capsules are obtained after filling.

[0091] Example 5

[0092] The prescription of Huperzine A Capsules described in this example is shown in Table 5.

[0093] Table 5 Prescription data of Huperzine A Capsules described in Example 5

[0094]

[0095]

[0096] The preparation method of Huperzine A capsule described in this embodiment:

[0097] S1: co-grinding: a portion of 150-mesh pregelatinized starch and 0.5 kg of huperzine A raw material were co-grinded to obtain a mixture 1.

[0098] S2: Wet granulation: Mixture 1 and the remaining 150 mesh pregelatinized starch are placed in a wet granulator, stirred at a speed of 200 rpm, and the cutting speed is 1200 rpm, and mixed for 5 minutes to be uniform; the peristaltic pump is turned on, and the atomization pressure is adjusted to 0.3 MPa. 2.8 kg of ethanol solution with a volume percentage of wetting agent of 1% is sprayed into the granulation pot at a speed of 300 rpm of the peristaltic pump. The spraying is completed within 3 minutes. The stirring speed is 200 rpm, the cutting speed is 1200 rpm, and the granulation is continued for 2 minutes. The soft material is passed through a 14-mesh sieve to obtain wet granules;

[0099] S3: Drying and granulation: The wet granules were placed in an oven and dried at a temperature below 60°C, with the granules turned over every 45 minutes. After drying for 2 hours, the granules were cooled and granulated in a swing granulator with a 50-mesh screen. After granulation, the granules were evenly spread on a drying tray again and dried for another 2 hours to obtain Huperzine A dry granules.

[0100] S4: Total mixing: 3.5 kg of silicon dioxide and additional 80 mesh lactose are premixed separately at a mass ratio of 1:10 and passed through a 50 mesh sieve; then, the mixture is placed in a hopper mixer with the huperzine A dry granules and the remaining 80 mesh lactose and mixed for 20 minutes at a mixing speed of 12 rpm to obtain huperzine A capsule granules, and the huperzine A capsules are obtained after filling.

[0101] Performance Testing:

[0102] (I) Mixing uniformity and central control dosage uniformity of Huperzine A capsule granules obtained in Example 1

[0103] The three batches of production processes of Example 1 were sampled and tested, and the test results are shown in Table 6. The bulk density of the particles after the total mixing was uniform and the mixing uniformity was good (≤5%). The samples of the filling process were tested for uniformity of the controlled dose. All single values ​​were between 75.0% and 125.0% of the target dose, and the mean value of each sampling point was between 90.0% and 110.0% of the target dose, with RSD≤6.0%.

[0104] Table 6 Mixing uniformity and control dose uniformity data of Huperzine A capsule granules obtained in Example 1

[0105]

[0106] (II) Batch-to-batch uniformity of the dissolution curve of Huperzine A capsule granules obtained in Example 1

[0107] Take three batches of products prepared in Example 1 and commercially available competing products, and select four media of pH 1.0 hydrochloric acid solution, pH 4.5 acetate buffer solution, pH 6.8 phosphate buffer solution and purified aqueous solution. According to the dissolution and release determination method of Appendix 0931 of Part II of the 2020 edition of the Chinese Pharmacopoeia (General Rule 0931 Method 3), the volume of the dissolution medium is 100 mL and the rotation speed is 35 revolutions per minute.

[0108] Table 7 Batch-to-batch uniformity of dissolution curve of Huperzine A capsule granules obtained in Example 1 (N=12)

[0109]

[0110] Table 8 Dissolution curve batch uniformity of commercially available competitive products (N=12)

[0111]

[0112] According to the data in Tables 7 and 8, by comparing the uniformity of the examples with the commercially available competitive products, it can be seen that the quality uniformity of the huperzine A capsule granules obtained in Example 1 is better than that of the commercially available competitive products.

[0113] (III) Stability test of Huperzine A capsule granules obtained in Example 1 (3 months)

[0114] The three batches of samples in Example 1 and commercially available huperzine A capsules were placed under long-term (temperature 25±2°C, humidity: 60±5%), intermediate conditions (temperature 30±2°C, relative humidity 65%±5%) and accelerated conditions (temperature 40±2°C, humidity: 75±5%).

[0115] Table 9 Stability experimental data of Huperzine A capsule granules obtained in Example 1

[0116]

[0117] From Table 9 above, it can be seen that the 3-month stability results of the three batches of samples in Example 1 are consistent with the dissolution trend, which meets the quality standard requirements; compared with commercially available competing products, the dissolution of the three batches of samples in Example 1 under intermediate conditions and accelerated conditions is better, indicating that the excellent dissolution effect can also be achieved when no disintegrant is added in the prescription of the present invention.

[0118] (IV) Sample stability of different addition methods of raw material Huperzine A

[0119] The stability of sample 240101 of Example 1 and sample FP22070101 of Comparative Example 1 were tested under accelerated conditions of 40° C. and 75% RH.

[0120] Table 10 Stability data of raw material Huperzine A under accelerated conditions (40°C, 75% RH) for samples with different addition methods

[0121]

[0122] Note: The total impurity data of the solid addition method of the raw material Huperzine A in this table are taken from the data in Table 11 where the mass ratio of internal filler: external filler is 1:3.

[0123] From the data comparison analysis of Table 10, it can be seen that when the raw material Huperzine A is added in solid form, the zero-day data of impurities becomes smaller and the increase slows down, and the sample stability is better than when it is added in solution form. Therefore, the method of the present invention determines to add the raw material Huperzine A in solid form, that is, take part of 200 mesh lactose and 0.01 kg of Huperzine A raw material and grind them together to add the Huperzine A raw material in the preparation method.

[0124] (V) Sample stability of internal and external fillers at different mass ratios

[0125] The stability of sample 240101 of Example 1 and three samples prepared with internal fillers and external fillers in different mass ratios of Comparative Example 2 were tested simultaneously under accelerated conditions of 40° C. and 75% RH.

[0126] Table 11 Stability data of samples with different mass ratios of internal fillers and external fillers under accelerated conditions (40°C, 75% RH)

[0127]

[0128] From the data in Table 11 and Figure 1-Figure 8 It can be seen that when the mass ratio of the internal filler to the external filler is 1:3, the huperzine A capsule particles have good uniformity and fluidity, and can ensure better stability of the huperzine A capsule.

[0129] (VI) In step (S2), in wet granulation, mixture 1 and the remaining 200 mesh lactose are placed in a wet granulator with a stirring speed of 200 rpm and a cutting speed of 1200 rpm. The effect of mixing time on mixing uniformity.

[0130] In Comparative Example 3, the mixing time was set at 3 min and 7 min respectively, and the mixing uniformity was tested.

[0131] Table 12 Premixing uniformity test results of Huperzine A capsule wet granulation

[0132]

[0133]

[0134] It can be seen from Table 12 that in step (S2) wet granulation, the mixing time must be ≥5 min to achieve the required mixing uniformity.

[0135] The above contents are further detailed descriptions of the present invention in combination with specific preferred embodiments, and the specific implementation of the present invention cannot be limited to these descriptions. For ordinary technicians in the field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the protection scope of the present invention.

Claims

1. A Huperzine A capsule, characterized in that: The composition comprises the following components in parts by weight: Huperzine A 0.01-0.5 parts by weight, 40.0-99.0 parts by weight of filler, wherein the filler is composed of internal filler and external filler; 0.4 to 4.5 parts by weight of glidant, The weight of the wetting agent is 10% to 14% of the weight of the internal filler; Wherein, the mesh number of the internal filler is smaller than the mesh number of the external filler, and the wetting agent is an ethanol solution.

2. The Huperzine A capsule according to claim 1, characterized in that: The mass ratio of the internal filler to the external filler is 1:

3.

3. The huperzine A capsule according to claim 1, characterized in that: The filler is selected from one or more of lactose, microcrystalline cellulose, starch, mannitol, and pregelatinized starch.

4. The huperzine A capsule according to claim 1, characterized in that: The mesh number of the filler is 80 meshes to 200 meshes.

5. The huperzine A capsule according to claim 1, characterized in that: The glidant is selected from one or both of silicon dioxide and colloidal silicon dioxide.

6. The method for preparing the Huperzine A capsule according to claim 1, characterized in that: The steps include: S1: co-crushing: the raw material Huperzine A and part of the internal filler are co-crushed to obtain a mixture 1; S2: Wet granulation: Transfer mixture 1 and the remaining internal filler to a wet granulator for mixing; start the peristaltic pump, spray the wetting agent into the granulation pot for stirring and granulation, and sieve the soft material to obtain wet granules; S3: Drying and granulation: The wet granules are placed in an oven for drying, and after cooling, they are granulated in an oscillating granulator. After granulation, they are spread on a drying tray again, and dried to obtain Huperzine A dry granules; S4: Total mixing: The flow aid and the additional filler are premixed separately at a mass ratio of 1:10, sieved, and then mixed with the huperzine A dry granules and the remaining additional filler in a hopper mixer to obtain huperzine A capsule granules, which are then filled to obtain huperzine A capsules.

7. The preparation method according to claim 6, characterized in that: In step S2, the atomization pressure of the peristaltic pump is 0.2-0.3 MPa; the rotation speed of the peristaltic pump is 250-350 rpm.

8. The preparation method according to claim 6, characterized in that: In step S2, the stirring speed of the granulating pot is 200 rpm, and the cutting speed is 1200 rpm.

9. The preparation method according to claim 6, characterized in that: In step S2, the soft material is screened with a mesh size of 12 to 20.

10. The preparation method according to claim 6, characterized in that: In step S4, in the hopper mixer, the mixing time is 10 to 20 minutes and the mixing speed is 8 to 12 rpm.

Images