CN116999400A - Isoniazid tablet and preparation method thereof - Google Patents
Isoniazid tablet and preparation method thereof Download PDFInfo
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- CN116999400A CN116999400A CN202311185707.XA CN202311185707A CN116999400A CN 116999400 A CN116999400 A CN 116999400A CN 202311185707 A CN202311185707 A CN 202311185707A CN 116999400 A CN116999400 A CN 116999400A
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- 229960003350 isoniazid Drugs 0.000 title claims abstract description 50
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000008187 granular material Substances 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 20
- 239000000945 filler Substances 0.000 claims abstract description 18
- 229920002472 Starch Polymers 0.000 claims abstract description 17
- 239000008107 starch Substances 0.000 claims abstract description 17
- 235000019698 starch Nutrition 0.000 claims abstract description 17
- 229920002261 Corn starch Polymers 0.000 claims abstract description 13
- 239000008120 corn starch Substances 0.000 claims abstract description 13
- 238000004806 packaging method and process Methods 0.000 claims abstract description 13
- 239000000853 adhesive Substances 0.000 claims abstract description 12
- 230000001070 adhesive effect Effects 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 11
- 229920001903 high density polyethylene Polymers 0.000 claims abstract description 11
- 239000004700 high-density polyethylene Substances 0.000 claims abstract description 11
- 229920000881 Modified starch Polymers 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims abstract description 10
- 239000011734 sodium Substances 0.000 claims abstract description 9
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 9
- 229940079593 drug Drugs 0.000 claims abstract description 8
- 239000000314 lubricant Substances 0.000 claims abstract description 7
- 238000005550 wet granulation Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims description 26
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- 238000007873 sieving Methods 0.000 claims description 11
- 239000002245 particle Substances 0.000 claims description 10
- 239000011265 semifinished product Substances 0.000 claims description 10
- 229910001220 stainless steel Inorganic materials 0.000 claims description 10
- 239000010935 stainless steel Substances 0.000 claims description 10
- 238000009835 boiling Methods 0.000 claims description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 6
- 238000007789 sealing Methods 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 3
- 239000005022 packaging material Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 238000005507 spraying Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 13
- 238000012360 testing method Methods 0.000 abstract description 7
- 239000007884 disintegrant Substances 0.000 abstract description 3
- 238000007906 compression Methods 0.000 abstract description 2
- 230000006835 compression Effects 0.000 abstract description 2
- 230000002950 deficient Effects 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 21
- 239000000203 mixture Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002609 medium Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 6
- 239000012736 aqueous medium Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010062207 Mycobacterial infection Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 208000022971 Tuberculous meningitis Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124976 antitubercular drug Drugs 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000001223 meningeal tuberculosis Diseases 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229940126589 solid medicine Drugs 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 239000000814 tuberculostatic agent Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/03—Containers specially adapted for medical or pharmaceutical purposes for pills or tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The application relates to the technical field of medicine preparation, in particular to isoniazid tablets and a preparation method thereof. The isoniazid tablet comprises the following main medicines and auxiliary materials in percentage by weight: 60 to 80 percent of main medicine, 15 to 30 percent of filler, 1 to 10 percent of adhesive, 1 to 5 percent of disintegrating agent and 0.5 to 5 percent of lubricant. According to the application, corn starch is used as a filler and an adhesive, pregelatinized starch is used as the filler, sodium carboxymethyl starch is used as a disintegrant for tabletting by a wet granulation process, and an oral solid high-density polyethylene bottle is used for packaging the preparation, so that related substances which are placed for 6 months from a product and a reference preparation under an accelerated test condition are unchanged from those of the related substances which are placed for 0 month. The prepared granules have uniform granularity, good fluidity and compression formability, low defective rate and excellent tablet core disintegration performance, and the prepared medicines are more stable by adopting the oral solid medicinal high-density polyethylene bottle for packaging.
Description
Technical Field
The application relates to the technical field of medicine preparation, in particular to isoniazid tablets and a preparation method thereof.
Background
Isoniazid is a synthetic antibacterial agent with bactericidal effect, and the isoniazid is only effective on mycobacteria, mainly on bacteria in growth and propagation period, and the action mechanism of isoniazid is not yet elucidated. The product is often combined with other antitubercular drugs, and is suitable for the treatment of various tuberculosis, including tubercular meningitis and other mycobacterial infections. Side effects are common peripheral neuritis symptoms such as dyspepsia, numbness or finger pain.
The product is commercially available from SANDOZ and 1952 in the United states under the trade name ISONIAZID. The reference preparation of the drug in the FDA is two tablets with the content of 100mg and 300 mg.
Isoniazid formula: c (C) 6 H 7 N 3 O, molecular weight: 137.14, structural formula:
the Chinese patent document publication number is CN109953956A, the patent name is a preparation method of isoniazid tablet, the application relates to a preparation method of isoniazid tablet: 1) The main components in parts by mass are: 50 parts of isoniazid, 20 parts of medicinal starch, 0.5 part of medicinal starch (for beating) and 0.21 part of magnesium stearate; 2) Pulping starch and a small amount of purified water to form paste, and slowly adding a sufficient amount of boiling purified water to prepare starch slurry; 3) Mixing isoniazid with medicinal starch for 15 min, adding the starch slurry, mixing for 10 min, and sieving with 16 mesh sieve; 4) Drying at 60-65 deg.c for 4 hr, sieving with 16 mesh sieve, and mixing with magnesium stearate for 15 min; 5) Tabletting is carried out by using a 5.5 shallow concave round die and hydraulic pressure of about 44 KN. In the prescription, only the pharmaceutical starch is used as a filling agent and a disintegrating agent, the dosage is large, the common starch has poor compressibility, the tablet is fragile and easy to crack at high concentration, and the quality control of the medicine is not facilitated, so that the medication safety of a patient is influenced.
Disclosure of Invention
The application aims at solving at least one of the technical problems existing in the prior art, and therefore, one aspect of the application aims at providing an isoniazid tablet, wherein the isoniazid tablet comprises the following main medicines and auxiliary materials in percentage by weight: 60 to 80 percent of main medicine, 15 to 30 percent of filler, 1 to 10 percent of adhesive, 1 to 5 percent of disintegrating agent and 0.5 to 5 percent of lubricant.
Preferably, the main medicine is isoniazid, the filler is corn starch and pregelatinized starch, the adhesive is corn starch, the disintegrating agent is carboxymethyl starch sodium and the lubricant is magnesium stearate; 10% -20% of corn starch and 5% -10% of pregelatinized starch.
Another aspect of the present application is to provide a method for preparing isoniazid tablets, which specifically comprises the following steps:
s1, crushing and sieving main raw material powder;
s2, placing the main medicine crushed and sieved in the S1, the filler and the disintegrating agent into a wet mixing granulator, uniformly mixing, spraying an adhesive, granulating, and wet finishing to obtain wet granules;
s3, drying the wet granules prepared in the step S2 in a multifunctional boiling granulator, and granulating by a granulator to prepare dry granules;
s4, placing the dry particles prepared in the S3 and the lubricant into a butt-clamp square cone mixer for uniform mixing to prepare total mixed particles, and checking a semi-finished product;
s5, placing the semi-finished product inspected in the S4 into a high-speed tablet press for tabletting to obtain isoniazid tablets;
s6, placing the tablets in the S5 into a bottling machine for sealing and packaging to obtain finished isoniazid tablets.
Preferably, in the step S1, the mixture is crushed and sieved by a 60-mesh sieve.
Preferably, the mixing speed of the main medicine, the filler and the disintegrating agent in the step S2 is 150rpm, the granulating cutter speed is 1500rpm, and the mixing time is 300S.
Preferably, the granulating speed of the adhesive sprayed in the step S2 is 100rpm, the rotating speed of the cutter is 1500rpm, and the granulating time is 60S; the wet granulation was a 6 x 6mm stainless steel screen with a rotation speed of 500rpm.
Preferably, in the S3, the frequency of a fan in the multifunctional boiling granulator is controlled to be 35-40 HZ, the air inlet temperature is 50+/-5 ℃, the material temperature is 38+/-2 ℃, and the moisture content is less than or equal to 3.0%; passing through a 1.5mm stainless steel screen with a rotational speed of 500rpm.
Preferably, the mixing speed in S4 is 10rpm and the mixing time is 300S.
Preferably, the standard of tabletting in the step S5 is 0.135g of tabletting by using a phi 6.5mm shallow concave punch, the main pressure of a tabletting machine is 10 KN-50 KN, and the hardness is controlled to be 30N-80N.
Preferably, the packaging material in S6 is a high-density polyethylene bottle for oral solid medicine, and the tablets are packaged in a packaging machine.
The application has the following beneficial effects:
according to the application, corn starch is used as a filler and an adhesive, pregelatinized starch is used as the filler, sodium carboxymethyl starch is used as a disintegrant for tabletting by a wet granulation process, and an oral solid high-density polyethylene bottle is used for packaging the preparation, so that related substances which are placed for 6 months from a product and a reference preparation under an accelerated test condition are unchanged from those of the related substances which are placed for 0 month. The prepared granules have uniform granularity, good fluidity and compression formability, low defective rate and excellent tablet core disintegration performance, and the prepared medicines are more stable by adopting the oral solid medicinal high-density polyethylene bottle for packaging.
The method has the advantages of short process steps, simpler and more convenient operation, improves the product yield, reduces the production cost and is suitable for industrial mass production.
Additional aspects and advantages of the application will become apparent in the following description or may be learned by practice of the application.
Drawings
The foregoing and/or additional aspects and advantages of the application will become apparent and may be better understood from the following description of embodiments taken in conjunction with the accompanying drawings in which:
FIG. 1 is a graph showing the dissolution of a first embodiment of the application and a reference formulation in hydrochloric acid and pH4.5 buffer;
FIG. 2 is a graph showing the dissolution of a first embodiment of the application and a reference formulation in pH6.8 buffer and water;
FIG. 3 is a graph showing the dissolution of the second and reference formulations of the present application in hydrochloric acid and pH4.5 buffer;
FIG. 4 is a graph showing the dissolution of a second embodiment of the application and a reference formulation in pH6.8 buffer and water;
FIG. 5 is a graph showing the dissolution of the third and reference formulations of the present application in hydrochloric acid and pH4.5 buffer;
FIG. 6 is a graph showing the dissolution of the third and reference formulations of the present application in pH6.8 buffer and water.
Detailed Description
In order that the above-recited objects, features and advantages of the present application will be more clearly understood, a more particular description of the application will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings. It should be noted that, without conflict, the embodiments of the present application and features in the embodiments may be combined with each other.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application, however, the present application may be practiced otherwise than as described, and therefore the scope of the present application is not limited to the specific embodiments disclosed below.
Example 1
Prescription information:
the preparation method comprises the following steps:
s1, crushing isoniazid and sieving the isoniazid with a 60-mesh sieve.
S2, placing crushed and sieved isoniazid, corn starch, pregelatinized starch and carboxymethyl starch sodium into an LHSZ-300 granule finishing wet mixing granulator, controlling the rotation speed to be 150rpm, the rotation speed of a granulating cutter to be 1500rpm, the mixing time to be 300s, granulating to be 100rpm, the rotation speed of a cutter to be 1500rpm and the granulating time to be 60s, and preparing wet granules by using a stainless steel screen with the wet granule finishing speed of 6mm and the rotation speed to be 500 rpm;
s3, placing the wet granules in an FBW80 multifunctional boiling granulator, controlling the fan frequency to be 35-40 HZ, the air inlet temperature to be 50+/-5 ℃, the material temperature to be 38+/-2 ℃ and the water content to be less than or equal to 3.0%; sieving with 1.5mm stainless steel screen, and granulating at 500rpm to obtain dry granule;
s4, placing the prepared dry particles and magnesium stearate into a HZD2000 opposite-clamping square cone mixer, controlling the rotating speed to be 10rpm and the mixing time to be 300s, preparing total mixed particles, and checking a semi-finished product;
s5, placing the inspected semi-finished product into a GZPS-73 high-speed tablet press, tabletting by using a phi 6.5mm shallow concave stamping die, wherein the main pressure of the tablet press is 10 KN-50 KN, and the hardness is controlled to be 30N-80N, so as to prepare isoniazid tablets;
s6, placing the tablets in a BZ-120 III bottling machine, sealing and packaging by adopting an oral solid medical high-density polyethylene bottle, and obtaining finished isoniazid tablets.
Example two
Prescription information:
the preparation method comprises the following steps:
s1, crushing isoniazid and sieving the isoniazid with a 60-mesh sieve.
S2, placing crushed and sieved isoniazid, corn starch, pregelatinized starch and carboxymethyl starch sodium into an LHSZ-300 granule finishing wet mixing granulator, controlling the rotation speed to be 150rpm, the rotation speed of a granulating cutter to be 1500rpm, the mixing time to be 300s, granulating to be 100rpm, the rotation speed of a cutter to be 1500rpm and the granulating time to be 60s, and preparing wet granules by using a stainless steel screen with the wet granule finishing speed of 6mm and the rotation speed to be 500 rpm;
s3, placing the wet granules in an FBW80 multifunctional boiling granulator, controlling the fan frequency to be 35-40 HZ, the air inlet temperature to be 50+/-5 ℃, the material temperature to be 38+/-2 ℃ and the water content to be less than or equal to 3.0%; sieving with 1.5mm stainless steel screen, and granulating at 500rpm to obtain dry granule;
s4, placing the prepared dry particles and magnesium stearate into a HZD2000 opposite-clamping square cone mixer, controlling the rotating speed to be 10rpm and the mixing time to be 300s, preparing total mixed particles, and checking a semi-finished product;
s5, placing the inspected semi-finished product into a GZPS-73 high-speed tablet press, tabletting by using a phi 6.5mm shallow concave stamping die, wherein the main pressure of the tablet press is 10 KN-50 KN, and the hardness is controlled to be 30N-80N, so as to prepare isoniazid tablets;
s6, placing the tablets in a BZ-120 III bottling machine, sealing and packaging by adopting an oral solid medical high-density polyethylene bottle, and obtaining finished isoniazid tablets.
Example III
Prescription information:
the preparation method comprises the following steps:
s1, crushing isoniazid and sieving the isoniazid with a 60-mesh sieve.
S2, placing the crushed and sieved isoniazid, corn starch and carboxymethyl starch sodium into an LHSZ-300 granule finishing wet mixing granulator, controlling the rotation speed to be 150rpm, the rotation speed of a granulating cutter to be 1500rpm, the mixing time to be 300s, granulating to be 100rpm, the rotation speed of a cutter to be 1500rpm, the granulating time to be 60s, and preparing wet granules by using a 6 x 6mm stainless steel screen with the rotation speed of 500 rpm;
s3, placing the wet granules in an FBW80 multifunctional boiling granulator, controlling the fan frequency to be 35-40 HZ, the air inlet temperature to be 50+/-5 ℃, the material temperature to be 38+/-2 ℃ and the water content to be less than or equal to 3.0%; sieving with 1.5mm stainless steel screen, and granulating at 500rpm to obtain dry granule;
s4, placing the prepared dry particles and magnesium stearate into a HZD2000 opposite-clamping square cone mixer, controlling the rotating speed to be 10rpm and the mixing time to be 300s, preparing total mixed particles, and checking a semi-finished product;
s5, placing the inspected semi-finished product into a GZPS-73 high-speed tablet press, tabletting by using a phi 6.5mm shallow concave stamping die, wherein the main pressure of the tablet press is 10 KN-50 KN, and the hardness is controlled to be 30N-80N, so as to prepare isoniazid tablets;
s6, placing the tablets in a BZ-120 III bottling machine, sealing and packaging by adopting an oral solid medical high-density polyethylene bottle, and obtaining finished isoniazid tablets.
Friability measurement:
the product was tested according to the friability test method of tablet 0923 in the chinese pharmacopoeia of 2020 edition, and the friability results are shown in table 1 below.
TABLE 1 comparison of friability results for example one, example two and example three
The friability of the tablet cores prepared by using water as a wetting agent in the second embodiment (lot number: G201202Y) does not meet the pharmacopoeia regulations (less than 1% weight loss in accordance with the Chinese pharmacopoeia of the 2020 edition), and both the first embodiment (lot number: G201201Y) and the third embodiment (lot number: G201203Y) meet the pharmacopoeia regulations.
Dissolution rate measurement:
the dissolution rate of the sample is measured according to the measurement method of the dissolution rate of isoniazid tablet in the Chinese pharmacopoeia of 2020 edition, and the medium is a reference preparation sample prepared by respectively using hydrochloric acid, pH4.5 buffer solution, pH6.8 buffer solution and water(lot number: 34033104A). The dissolution results are shown in tables 2 to 7, and the dissolution curves are shown in fig. 1 to 6.
TABLE 2 comparison of the dissolution results of example one with the reference formulation in hydrochloric acid and pH4.5 medium
TABLE 3 comparison of the dissolution results of example one with the reference formulation in pH6.8 medium and in aqueous medium
TABLE 4 comparison of the dissolution results of example two with the reference formulation in hydrochloric acid and pH4.5 medium
TABLE 5 comparison of the dissolution results of example two with the reference formulation in pH6.8 medium and in aqueous medium
TABLE 6 comparison of the dissolution results of the three reference formulations of example III in hydrochloric acid and pH4.5 medium
TABLE 7 comparison of the dissolution results of example III with reference formulation in pH6.8 medium and aqueous medium
Dissolution and reference formulations of examples one and twoThe dissolution behavior is completely consistent, and the dissolution rate of the third embodiment is obviously slow compared with that of the reference preparation.
The first embodiment has simple and feasible preparation process and is easy to realize industrialized mass production.
The stability of the product of the application was studied:
referring to the principle of guiding stability test of bulk drugs and pharmaceutical preparations in the "Chinese pharmacopoeia" 2020 edition, samples of the first, second and third examples were taken and placed under the condition of acceleration test (40 ℃ + -2 ℃ C., 75% + -5% RH) for 6 months respectively, the change trend of the related substances of the samples was examined, and compared with the data of day 0, and the results of the related substances of each batch of samples are shown in Table 8.
The corn starch is used as a filling agent and an adhesive, the pregelatinized starch is used as a filling agent, the carboxymethyl starch sodium is used as a disintegrating agent for tabletting by a wet granulation process, and the oral solid high-density polyethylene bottle is used for packaging the preparation, so that related substances which are placed for 6 months under the accelerated test condition from the preparation and a reference preparation are unchanged from those of the related substances which are placed for 0 month.
TABLE 8 results of substances related to each lofting condition
The related substances of the first embodiment and the second embodiment are respectively placed for 6 months under the accelerated test condition, and compared with the related substances of the second embodiment and the third embodiment, the related substances of the third embodiment are unchanged, and the other single impurities and the total impurities of the third embodiment are obviously increased.
The test results show that the dissolution behavior of the first example and the reference preparation in hydrochloric acid, pH4.5 buffer solution, pH6.8 buffer solution and aqueous medium is similar to that of the reference preparation; the relevant substances of example one and the reference formulation were unchanged from those of example 0 month when placed under accelerated test conditions for 6 months. This shows that the wet granulation process using corn starch as filler and binder, pregelatinized starch as filler, and sodium carboxymethyl starch as disintegrant, tableted, packaged formulations using oral solid high density polyethylene bottles, were of similar quality from the product to the reference formulation.
The above description is only of the preferred embodiments of the present application and is not intended to limit the present application, but various modifications and variations will be apparent to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims (10)
1. An isoniazid tablet, characterized in that: the isoniazid tablet comprises the following main medicines and auxiliary materials in percentage by weight: 60 to 80 percent of main medicine, 15 to 30 percent of filler, 1 to 10 percent of adhesive, 1 to 5 percent of disintegrating agent and 0.5 to 5 percent of lubricant.
2. An isoniazid tablet according to claim 1 characterized in that: the main medicine is isoniazid, the filler is corn starch and pregelatinized starch, the adhesive is corn starch, the disintegrating agent is carboxymethyl starch sodium and the lubricant is magnesium stearate; 10% -20% of corn starch and 5% -10% of pregelatinized starch.
3. The method for preparing isoniazid tablets according to claim 1, characterized in that: the preparation method comprises the following specific steps:
s1, crushing and sieving main raw material powder;
s2, placing the main medicine crushed and sieved in the S1, the filler and the disintegrating agent into a wet mixing granulator, uniformly mixing, spraying an adhesive, granulating, and wet finishing to obtain wet granules;
s3, drying the wet granules prepared in the step S2 in a multifunctional boiling granulator, and granulating by a granulator to prepare dry granules;
s4, placing the dry particles prepared in the S3 and the lubricant into a butt-clamp square cone mixer for uniform mixing to prepare total mixed particles, and checking a semi-finished product;
s5, placing the semi-finished product inspected in the S4 into a high-speed tablet press for tabletting to obtain isoniazid tablets;
s6, placing the tablets in the S5 into a bottling machine for sealing and packaging to obtain finished isoniazid tablets.
4. A method for preparing isoniazid tablets according to claim 3 characterized by: and (3) crushing the materials in the step S1, and sieving the crushed materials with a 60-mesh sieve.
5. A method for preparing isoniazid tablets according to claim 3 characterized by: and in the step S2, the mixing speed of the main medicine, the filler and the disintegrating agent is 150rpm, the speed of a granulating cutter is 1500rpm, and the mixing time is 300S.
6. A method for preparing isoniazid tablets according to claim 3 characterized by: the granulating speed of the adhesive sprayed in the step S2 is 100rpm, the rotating speed of the cutter is 1500rpm, and the granulating time is 60S; the wet granulation was a 6 x 6mm stainless steel screen with a rotation speed of 500rpm.
7. A method for preparing isoniazid tablets according to claim 3 characterized by: the frequency of a fan in the multifunctional boiling granulator in the step S3 is controlled to be 35-40 HZ, the air inlet temperature is 50+/-5 ℃, the material temperature is 38+/-2 ℃, and the moisture content is less than or equal to 3.0%; passing through a 1.5mm stainless steel screen with a rotational speed of 500rpm.
8. A method for preparing isoniazid tablets according to claim 3 characterized by: the mixing speed in the step S4 is 10rpm, and the mixing time is 300S.
9. A method for preparing isoniazid tablets according to claim 3 characterized by: and the standard of tabletting in the step S5 is 0.135g of each tablet, the tablet is stamped by using a shallow concave with the diameter of 6.5mm, the main pressure of the tablet press is 10 KN-50 KN, and the hardness is controlled to be 30N-80N.
10. A method for preparing isoniazid tablets according to claim 3 characterized by: and S6, packaging the tablets in a packaging machine, wherein the packaging material in the S6 is an oral solid medical high-density polyethylene bottle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311185707.XA CN116999400A (en) | 2023-09-14 | 2023-09-14 | Isoniazid tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311185707.XA CN116999400A (en) | 2023-09-14 | 2023-09-14 | Isoniazid tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116999400A true CN116999400A (en) | 2023-11-07 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311185707.XA Pending CN116999400A (en) | 2023-09-14 | 2023-09-14 | Isoniazid tablet and preparation method thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN116999400A (en) |
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2023
- 2023-09-14 CN CN202311185707.XA patent/CN116999400A/en active Pending
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