Isoniazide tablet and preparation method thereof

Abstract

The invention relates to the technical field of pharmacy, and provides an isoniazide tablet and a preparation method thereof.The isoniazide tablet comprises isoniazide, microcrystalline cellulose, pregelatinized starch, polyvinylpolypyrrolidone, colloidal silicon dioxide, magnesium stearate and hydrogenated vegetable oil; the preparation method comprises the following steps: weighing the raw material components according to the mass ratio, and sequentially adding the isoniazide and the colloidal silicon dioxide into a mixer for mixing; sequentially adding microcrystalline cellulose, pregelatinized starch, cross-linked povidone and the pretreated hydrogenated vegetable oil into the mixing machine, and mixing the microcrystalline cellulose, the pregelatinized starch, the cross-linked povidone and the pretreated hydrogenated vegetable oil; finally, magnesium stearate is added into the mixing machine to be mixed, and a mixed material is obtained; the isoniazide tablet which is good in compressibility, not easy to break, low in impurity content and excellent in performance is prepared by strictly regulating and controlling the components and the content of the isoniazide tablet and controlling specific parameters of the steps of raw material mixing, tabletting and the like in the production process, and the isoniazide tablet has higher safety and is more beneficial to the use of isoniazide as an anti-tuberculosis first-line medicine.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to isoniazid tablets and a preparation method thereof. Background Art

[0002] Isoniazid is a synthetic antibacterial drug with bactericidal effects. It is only effective against mycobacteria, mainly bacteria in the growth and reproduction stage. Its mechanism of action has not yet been elucidated. Isoniazid is often combined with other anti-tuberculosis drugs and is suitable for the treatment of various types of tuberculosis, including tuberculous meningitis and other mycobacterial infections. Common side effects include indigestion and peripheral neuritis symptoms such as numbness or finger pain. The original developer of isoniazid tablets is SANDOZ, which was first launched in the United States in 1952 under the trade name I SONIAZ ID. Its reference preparations at the US Food and Drug Administration are two tablets with isoniazid contents of 100 mg and 300 mg.

[0003] The Chinese patent with publication number CN109953956A discloses a method for preparing isoniazid tablets, the mass fractions of the main components of which are: 50 parts of isoniazid, 20 parts of medicinal starch, 0.5 parts of medicinal starch (for beating), and 0.21 parts of magnesium stearate. During preparation, the starch for beating is mixed with a small amount of purified water into a paste, and then a sufficient amount of boiling purified water is slowly added to obtain starch slurry. After mixing isoniazid with medicinal starch for 15 minutes, the above-mentioned starch slurry is added and mixed for 10 minutes, and then passed through a 16-mesh sieve; dried at 60°C-65°C for 4 hours, granulated with a 16-mesh sieve, and then magnesium stearate is added and mixed for 15 minutes; a 5.5 shallow concave circular punch is used, and the hydraulic pressure is about 44KN for tableting. In the patent prescription, only medicinal starch is used as a filler and disintegrant and the dosage is large. Ordinary starch has poor compressibility, and the tablets are fragile and easy to top crack at high concentrations. Therefore, it is not conducive to the quality control of the drug, which will affect the patient's medication safety.

[0004] A Chinese patent with publication number CN108186638A discloses an isoniazid composition and a preparation method thereof. The preparation method of the patent adopts wet granulation technology, and lactose is used as a filler in the patent. The hydroxyl group in the lactose reacts with the primary amino group in isoniazid to produce hydrazine. If the adjuvants different from those involved in the patent are selected and the sample is prepared by the wet granulation process, water is added during the wet granulation process, and it is dried at a high temperature, and isoniazid itself is unstable and is easily affected by factors such as temperature, light, heavy metals, pH, and water. Therefore, the wet granulation technology will produce higher impurities and affect the patient's medication safety.

[0005] Therefore, in order to overcome the defects of the above-mentioned isoniazid preparations, the present invention proposes an isoniazid tablet and a preparation method thereof, so that the product has higher safety and lower risk of side effects, which is more conducive to the use of isoniazid as a first-line drug for anti-tuberculosis. Summary of the invention

[0006] The invention provides an isoniazid tablet and a preparation method thereof, which solves the problem in the related art that the drug quality and safety of isoniazid tablets need to be improved.

[0007] The technical solution of the present invention is as follows:

[0008] In a first aspect, the present invention discloses an isoniazid tablet comprising the following raw material components in the following mass ratios:

[0009] Isoniazid 50.0%, microcrystalline cellulose 43.5%, pregelatinized starch 1.5%, cross-linked polyvinylpyrrolidone 1.0%, colloidal silicon dioxide 2.5%, magnesium stearate 1.3%, hydrogenated vegetable oil 0.2%.

[0010] In a second aspect, the present invention further discloses a method for preparing the isoniazid tablets as described above, comprising the following steps:

[0011] S1: Weigh the raw material components according to the mass ratio, first add isoniazid and colloidal silicon dioxide into the mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; then add microcrystalline cellulose, pregelatinized starch, cross-linked polyvinylpyrrolidone and pretreated hydrogenated vegetable oil into the mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; finally add magnesium stearate into the mixer, and mix at a speed of 12 r / min for 3 minutes to obtain a mixture;

[0012] Preferably, the mixer is an automatic lifting hopper mixer.

[0013] Furthermore, isoniazid is pretreated before being weighed, and the pretreatment method is: crushing the isoniazid raw material components, and then passing the crushed isoniazid through a 60-mesh sieve.

[0014] Furthermore, the hydrogenated vegetable oil is pretreated before being weighed, and the pretreatment method is: passing the hydrogenated vegetable oil through an 80-mesh sieve.

[0015] S2: using a punch to compress the mixed material into tablets to obtain isoniazid tablets;

[0016] Preferably, the unit weight specifications of isoniazid tablets include 0.6g and 0.2g.

[0017] Furthermore, when the unit weight specification of isoniazid tablets is 0.6g, an elliptical punch with a long diameter of 18mm, a short diameter of 8.5mm and a drug separation line on one side is used for tableting. The machine speed is 50,000-90,000 tablets / h and the average pressure is 19KN-35KN.

[0018] Furthermore, the standards for controlling the quality of isoniazid tablets are as follows: the appearance of the tablets is checked during the tableting process, the tablet weight difference is controlled within ±4%, the hardness range is measured by the short diameter and is controlled within 120-160N, and the friability is controlled within ≤0.8%.

[0019] Furthermore, when the unit weight specification of isoniazid tablets is 0.2g, a round punch with a diameter of 18mm and a drug separation line on one side is used for tableting, the machine speed is 50,000-90,000 tablets / h, and the average pressure is 9KN-15KN.

[0020] Furthermore, the standards for controlling the quality of isoniazid tablets are as follows: the appearance of the tablets is checked during the tableting process, the tablet weight difference is controlled within ±6%, the hardness range is measured by the short diameter and is controlled within 40-70N, and the friability is controlled within ≤0.8%.

[0021] S3: Packing the isoniazid tablets in plastic bottles;

[0022] Preferably, the specification of the inner packaging of the plastic bottle is 100 pieces / bottle.

[0023] As a further technical solution,

[0024] The working principle and beneficial effects of the present invention are:

[0025] The invention strictly regulates the components and content of isoniazid tablets and controls the specific parameters of steps such as raw material mixing and tablet pressing in the production process, so as to prepare isoniazid tablets with good compressibility, low impurity content and high safety, and is more conducive to the use of isoniazid as a first-line anti-tuberculosis drug. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.

[0027] Figure 1 The present invention is a flow chart of the preparation of isoniazid tablets. DETAILED DESCRIPTION

[0028] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] The invention discloses an isoniazid tablet, comprising the following raw material components in the following mass ratio:

[0030] Isoniazid 50.0%, microcrystalline cellulose 43.5%, pregelatinized starch 1.5%, cross-linked polyvinylpyrrolidone 1.0%, colloidal silicon dioxide 2.5%, magnesium stearate 1.3%, hydrogenated vegetable oil 0.2%.

[0031] See also Figure 1 , prepare isoniazid tablets according to the following steps:

[0032] Step 1: Weigh each raw material component according to the mass ratio, first add isoniazid and colloidal silicon dioxide into the automatic lifting hopper mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; then add microcrystalline cellulose, pregelatinized starch, cross-linked polyvinylpyrrolidone and pretreated hydrogenated vegetable oil into the automatic lifting hopper mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; finally, add magnesium stearate into the automatic lifting hopper mixer, and mix at a speed of 12 r / min for 3 minutes to obtain a mixture;

[0033] Wherein, isoniazid is pretreated before being weighed, and the pretreatment method is: crushing the isoniazid raw material components, and passing the crushed isoniazid through a 60-mesh sieve; hydrogenated vegetable oil is also pretreated before being weighed, and the pretreatment method is: passing the hydrogenated vegetable oil through an 80-mesh sieve.

[0034] Step 2: using a punch to compress the mixed material into tablets to obtain isoniazid tablets;

[0035] Preferably, the unit weight specifications of isoniazid tablets include 0.6g (isoniazid 0.3g) and 0.2g (isoniazid 0.1g).

[0036] When the unit weight specification of isoniazid tablets is 0.6g, an elliptical punch with a long diameter of 18mm, a short diameter of 8.5mm and a drug separation line on one side is used for tableting. The machine speed is 50,000-90,000 tablets / h and the average pressure is 19KN-35KN. During the tableting process, the appearance of the tablets is checked, the tablet weight difference is controlled within ±4%, the hardness range is measured with the short diameter and is controlled within 120-160N, and the friability is controlled within ≤0.8%.

[0037] When the unit weight specification of isoniazid tablets is 0.2g, a round punch with a diameter of 18mm and a drug separation line on one side is used for tableting, the machine speed is 50,000-90,000 tablets / h, and the average pressure is 9KN-15KN; further, the standard for controlling the qualified isoniazid tablets is: the appearance of the tablets is checked during the tableting process, the tablet weight difference is controlled within ±6%, the hardness range is measured by the short diameter and is controlled within 40-70N, and the friability is controlled within ≤0.8%.

[0038] Step 3: Use medicinal high-density ethylene bottles to package the isoniazid tablets in plastic bottles, and the specification of the plastic bottle packaging is 100 tablets / bottle.

[0039] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0040] Example 1

[0041] Prepare 150,000 isoniazid tablets with a unit weight of 0.6g.

[0042] Step 1: Weigh 45kg of isoniazid, 39.15kg of microcrystalline cellulose, 1.35kg of pregelatinized starch, 0.9kg of cross-linked polyvinylpyrrolidone, 2.25kg of colloidal silicon dioxide, 1.17kg of magnesium stearate, and 0.18kg of hydrogenated vegetable oil; wherein, isoniazid is crushed and passed through a 60-mesh sieve before weighing, and hydrogenated vegetable oil is passed through an 80-mesh sieve before weighing; first, add isoniazid and colloidal silicon dioxide to an automatic lifting hopper mixer in sequence, and mix at a speed of 12r / min for 5min; then, add microcrystalline cellulose, pregelatinized starch, cross-linked polyvinylpyrrolidone and pretreated hydrogenated vegetable oil to the automatic lifting hopper mixer in sequence, and mix at a speed of 12r / min for 5min; finally, add magnesium stearate to the automatic lifting hopper mixer, and mix at a speed of 12r / min for 3min to obtain a mixture;

[0043] Step 2: Use an elliptical punch with a long diameter of 18mm, a short diameter of 8.5mm and a drug separation line on one side for tableting, with a machine speed of 70,000 tablets / h and an average pressure of 27KN; check the appearance of the tablets during tableting, and control the tablet weight difference within ±4%, the hardness range is measured by the short diameter and controlled within 120-160N, and the friability is controlled within ≤0.8%;

[0044] Step 3: The isoniazid tablets are packaged in plastic bottles at a specification of 100 tablets / bottle, and the plastic bottles are made of medicinal high-density ethylene bottles.

[0045] Example 2

[0046] Prepare 200,000 isoniazid tablets with a unit weight specification of 0.2g.

[0047] Step 1: weigh 20kg of isoniazid, 17.4kg of microcrystalline cellulose, 0.6kg of pregelatinized starch, 0.4kg of cross-linked polyvinylpyrrolidone, 1kg of colloidal silicon dioxide, 0.52kg of magnesium stearate, and 0.08kg of hydrogenated vegetable oil; wherein, isoniazid is crushed and passed through a 60-mesh sieve before weighing, and hydrogenated vegetable oil is passed through an 80-mesh sieve before weighing; first, add isoniazid and colloidal silicon dioxide to an automatic lifting hopper mixer in sequence, and mix at a speed of 12r / min for 5min; then, add microcrystalline cellulose, pregelatinized starch, cross-linked polyvinylpyrrolidone and pretreated hydrogenated vegetable oil to the automatic lifting hopper mixer in sequence, and mix at a speed of 12r / min for 5min; finally, add magnesium stearate to the automatic lifting hopper mixer, and mix at a speed of 12r / min for 3min to obtain a mixture;

[0048] Step 2: Use a round punch with a diameter of 18mm and a drug separation line on one side for tableting, with a machine speed of 50,000-90,000 tablets / h and an average pressure of 9KN-15KN; check the appearance of the tablets during tableting, and control the tablet weight difference within ±6%, the hardness range is measured by the short diameter and controlled within 40-70N, and the friability is controlled within ≤0.8%;

[0049] Step 3: The isoniazid tablets are packaged in plastic bottles at a specification of 100 tablets / bottle, and the plastic bottles are made of medicinal high-density ethylene bottles.

[0050] Two bottles of isoniazid tablets were randomly selected for spot check of the isoniazid tablets prepared in Examples 1-2, and the isoniazid tablets sampled were recorded as Example 1-A, Example 1-B, Example 2-A, and Example 2-B, respectively. Subsequently, the four groups of isoniazid tablets were quality tested, and the quality results of isoniazid tablets (reference preparation) issued by the State Food and Drug Administration were used as benchmark indicators. A limit range was determined on the basis of the benchmark indicators as the quality standard to determine whether the prepared isoniazid tablets were within the range of the quality standard; the test results are listed in Table 1 (ND stands for not detected), which is as follows:

[0051] Table 1

[0052]

[0053]

[0054] By analyzing the data in Table 1, it can be seen that the isoniazid tablets prepared in Examples 1-2 all meet the quality standards and have better quality.

[0055] Five bottles of isoniazid tablets were randomly selected for spot check of the isoniazid tablets prepared in Example 1-2. The isoniazid tablets sampled were recorded as Example 1-1, Example 1-2, Example 1-3, Example 1-4, Example 1-5, Example 2-1, Example 2-2, Example 2-3, Example 2-4, and Example 2-5, respectively. Subsequently, the dissolution rates of the ten groups of isoniazid tablets in various media were tested, and the quality results of isoniazid tablets (reference preparation) issued by the State Food and Drug Administration were used as benchmark indicators. A limit range was determined on the basis of the benchmark indicators as the quality standard to determine whether the prepared isoniazid tablets were within the range of the quality standard. The test results are listed in Table 2, which is as follows:

[0056] Table 2

[0057]

[0058]

[0059] By analyzing the data in Table 2, it can be seen that the dissolution rates of the isoniazid tablets prepared in Examples 1-2 in various media all meet the quality standards, and the dissolution rates are relatively higher.

[0060] One bottle of isoniazid tablets prepared in Examples 1-2 was randomly selected for spot check and subjected to long-term testing under conditions of 30°C ± 2°C and RH 65% ± RH 5%. The test results of Example 1 are listed in Table 3 and the test results of Example 2 are listed in Table 4. Tables 3-4 are as follows:

[0061] Table 3

[0062]

[0063] Table 4

[0064]

[0065]

[0066] By analyzing the data in Table 3-4, it can be seen that the isoniazid tablets prepared in Example 1-2 still meet the standards after six months of long-term testing.

[0067] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An isoniazid tablet, characterized in that: The raw material components include the following mass ratios: Isoniazid 50.0%, microcrystalline cellulose 43.5%, pregelatinized starch 1.5%, cross-linked polyvinylpyrrolidone 1.0%, colloidal silicon dioxide 2.5%, magnesium stearate 1.3%, hydrogenated vegetable oil 0.2%.

2. A method for preparing isoniazid tablets as claimed in claim 1, characterized in that: The following steps are involved: S1: Weigh the raw material components according to the mass ratio, first add isoniazid and colloidal silicon dioxide into the mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; then add microcrystalline cellulose, pregelatinized starch, cross-linked polyvinylpyrrolidone and pretreated hydrogenated vegetable oil into the mixer in sequence, and mix at a speed of 12 r / min for 5 minutes; finally add magnesium stearate into the mixer, and mix at a speed of 12 r / min for 3 minutes to obtain a mixture; S2: using a punch to compress the mixed material into tablets to obtain isoniazid tablets; S3: Pack the isoniazid tablets in plastic bottles.

3. The method for preparing isoniazid tablets according to claim 2, characterized in that: In step S2, the unit weight specifications of isoniazid tablets include 0.6g and 0.2g.

4. The method for preparing isoniazid tablets according to claim 3, characterized in that: When the unit weight specification of isoniazid tablets is 0.6g, an elliptical punch with a long diameter of 18mm, a short diameter of 8.5mm and a drug separation line on one side is used for tableting. The machine speed is 50,000-90,000 tablets / h and the average pressure is 19KN-35KN.

5. The method for preparing isoniazid tablets according to claim 4, characterized in that: The standards for controlling the quality of isoniazid tablets are as follows: the appearance of the tablets is checked during the tableting process, the tablet weight difference is controlled within ±4%, the hardness range is measured by the short diameter and is controlled within 120-160N, and the friability is controlled within ≤0.8%.

6. The method for preparing isoniazid tablets according to claim 4, characterized in that: When the unit weight specification of isoniazid tablets is 0.2g, a round punch with a diameter of 18mm and a drug separation line on one side is used for tableting. The machine speed is 50,000-90,000 tablets / h and the average pressure is 9KN-15KN.

7. The method for preparing isoniazid tablets according to claim 6, characterized in that: The standards for controlling the quality of isoniazid tablets are as follows: the appearance of the tablets is checked during the tableting process, the tablet weight difference is controlled within ±6%, the hardness range is measured by the short diameter and is controlled within 40-70N, and the friability is controlled within ≤0.8%.

8. The method for preparing isoniazid tablets according to claim 2, characterized in that: In step S1, isoniazid is pretreated before being weighed, and the pretreatment method is: the isoniazid raw material component is crushed, and the crushed isoniazid is passed through a 60-mesh sieve.

9. The method for preparing isoniazid tablets according to claim 2, characterized in that: In step S1, the hydrogenated vegetable oil is pretreated before being weighed. The pretreatment method is: passing the hydrogenated vegetable oil through an 80-mesh sieve.

10. The method for preparing isoniazid tablets according to claim 2, characterized in that: In step S3, the specification of the inner packaging of the plastic bottle is 100 pieces / bottle.

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