CN115844840B - Paracetamol tablet and preparation method thereof - Google Patents
Paracetamol tablet and preparation method thereof Download PDFInfo
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- CN115844840B CN115844840B CN202211565160.1A CN202211565160A CN115844840B CN 115844840 B CN115844840 B CN 115844840B CN 202211565160 A CN202211565160 A CN 202211565160A CN 115844840 B CN115844840 B CN 115844840B
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- pregelatinized starch
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 title claims abstract description 206
- 229960005489 paracetamol Drugs 0.000 title claims abstract description 121
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000000853 adhesive Substances 0.000 claims abstract description 16
- 238000009835 boiling Methods 0.000 claims abstract description 16
- 239000000314 lubricant Substances 0.000 claims abstract description 14
- 239000000945 filler Substances 0.000 claims abstract description 13
- 230000001070 adhesive effect Effects 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 229920000881 Modified starch Polymers 0.000 claims description 63
- 239000008187 granular material Substances 0.000 claims description 32
- 238000003756 stirring Methods 0.000 claims description 31
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 30
- 238000002156 mixing Methods 0.000 claims description 30
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 29
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 29
- 229940069328 povidone Drugs 0.000 claims description 29
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 26
- 239000002002 slurry Substances 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 238000001035 drying Methods 0.000 claims description 20
- 239000008213 purified water Substances 0.000 claims description 15
- 239000011268 mixed slurry Substances 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 238000005303 weighing Methods 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 6
- 238000010981 drying operation Methods 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 abstract description 24
- 239000003814 drug Substances 0.000 abstract description 19
- 239000000463 material Substances 0.000 abstract description 13
- 229940079593 drug Drugs 0.000 abstract description 9
- 239000007884 disintegrant Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000001647 drug administration Methods 0.000 abstract description 3
- 238000011156 evaluation Methods 0.000 abstract description 3
- 239000004094 surface-active agent Substances 0.000 abstract description 3
- 238000007689 inspection Methods 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000003168 generic drug Substances 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 25
- 238000012360 testing method Methods 0.000 description 9
- 238000005520 cutting process Methods 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 238000007906 compression Methods 0.000 description 6
- 230000006835 compression Effects 0.000 description 6
- 238000012797 qualification Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000010241 potassium sorbate Nutrition 0.000 description 4
- 229940069338 potassium sorbate Drugs 0.000 description 4
- 239000004302 potassium sorbate Substances 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 3
- 238000005336 cracking Methods 0.000 description 3
- 238000007580 dry-mixing Methods 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010041662 Splinter Diseases 0.000 description 2
- 239000003907 antipyretic analgesic agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种对乙酰氨基酚片及其制备方法，属于药物制剂制备技术领域。按重量份数计，该对乙酰氨基酚片包括对乙酰氨基酚86.88份、粘合剂4.52份、崩解剂2.90份、填充剂5.21份和润滑剂0.49份。本发明通过改良对乙酰氨基酚片的配方和结合特殊的制备工艺，减少了辅料种类及用量，主药占比高，同时制备工艺简单，生产成本低，安全生产，不需要沸水或有机溶剂配浆，机械化程度高，适合工业化生产，解决了对乙酰氨基酚片可压性差的问题，制备得到的乙酰氨基酚片片重小，可以最大限度减少辅料的管理和检验成本，提高患者用药的顺应性，并且，产品质量稳定，溶出完全，质量与原研制剂一致，同时不含表面活性剂，符合国家药品监督管理局仿制药一致性评价BE豁免要求。The invention discloses an acetaminophen tablet and a preparation method thereof, and belongs to the technical field of pharmaceutical preparation preparation. By weight, the acetaminophen tablet includes 86.88 parts of acetaminophen, 4.52 parts of adhesive, 2.90 parts of disintegrant, 5.21 parts of filler and 0.49 parts of lubricant. The present invention reduces the types and amounts of auxiliary materials by improving the formula of acetaminophen tablets and combining a special preparation process, and the main drug accounts for a high proportion. At the same time, the preparation process is simple, the production cost is low, and the production is safe. It does not require boiling water or organic solvent slurrying, and the degree of mechanization is high. It is suitable for industrial production, solves the problem of poor compressibility of acetaminophen tablets, and the prepared acetaminophen tablets are small in weight, which can minimize the management and inspection costs of auxiliary materials, improve the compliance of patients with medication, and the product quality is stable, the dissolution is complete, the quality is consistent with the original preparation, and it does not contain surfactants, which meets the BE exemption requirements of the generic drug consistency evaluation of the State Drug Administration.
Description
Technical Field
The invention relates to the technical field of preparation of pharmaceutical preparations, in particular to a paracetamol tablet and a preparation method thereof.
Background
Acetaminophen (Paracetamol), known as 4' -hydroxyacetanilide, has a molecular formula of C 8H9NO2, is an antipyretic analgesic, and is effective in relieving fever by inhibiting cyclooxygenase, selectively inhibiting synthesis of central prostaglandins of hypothalamic thermoregulation, and causing peripheral vasodilation and sweating.
In 1878, harmon Northrop Morse was the first synthesis of acetaminophen at john hopkins university. Acetaminophen is marketed both at home and abroad and has been marketed as a non-prescription drug for many years at home. The acetaminophen has the characteristics of rapid and complete oral absorption, small toxic and side effects, safe use and the like, and is the non-prescription antipyretic analgesic with the most widely used international application and the greatest dosage. The acetaminophen crystal belongs to brittle broken materials, has typical molar body compression characteristics, takes the shape of long needle crystals, has larger brittleness, weak plastic deformation capability, poor compressibility, easy occurrence of cracking or cover falling during tabletting, and the like, and influences the quality of products. And because the acetaminophen tablet has larger specification (0.5 g), if excessive auxiliary materials are used, the tablet weight and the volume are overlarge, so that a certain difficulty is caused to swallowing when a patient takes the medicine, the medicine compliance of the patient is reduced, and the treatment of diseases is not facilitated. However, the acetaminophen tablet generally requires that the acetaminophen content be more than 85%, the acetaminophen has poor compressibility and high content, the auxiliary material space is small, the acetaminophen is easy to hydrolyze in a high-humidity environment, the tablet weight of the acetaminophen tablet is reduced, and the preparation process of the acetaminophen tablet is a challenge.
A reference formulation for acetaminophen tablets (0.5 g) published by the national drug administration was a reference formulation for GlaxoSmithKline Consumer Healthcare company to produce and supply the global marketThe tablet core comprises acetaminophen, corn starch, pregelatinized starch, potassium sorbate, povidone, stearic acid and talcum powder.
Chinese patent document CN110496107A discloses a acetaminophen tablet and a preparation method thereof, wherein the acetaminophen tablet comprises, by weight, 1100-12500 parts of acetaminophen, 46-50 parts of povidone K30, 160-176 parts of purified water, 120-136 parts of pregelatinized starch, 9.1-9.9 parts of stearic acid and 2.9-3.5 parts of magnesium stearate as lubricants, and the preparation method uses stearic acid and magnesium stearate as lubricants, but the mixing time is 25min, and excessive mixing of magnesium stearate is caused due to excessive mixing time, so that the tablet splitting of the product is easy to cause, The dissolution rate is reduced, chinese patent document CN108853038A discloses a acetaminophen tablet and a preparation process thereof, which comprises the following steps of adding potassium sorbate into purified water to dissolve to prepare potassium sorbate solution, adding acetaminophen, pregelatinized starch, calcium carbonate, povidone K30 and crospovidone into a high-efficiency wet granulator to be premixed for 3min, adding potassium sorbate solution into the premixed powder to be continuously stirred for 2min to prepare wet granules, placing the wet granules into a boiling granulating dryer to be dried, controlling the drying temperature to be 90-100 ℃ and the water content to be 1-3%, preparing granules, finishing the dry granules to prepare 16-mesh granules, adding the granules into a mixer, adding alginic acid, mixing silicon dioxide and magnesium stearate in a closed way for 20min, and setting the rotating speed of a mixer to be 10 revolutions per minute; tabletting and sieving the mixed particles to obtain the granules; the prescription is complex, the types of auxiliary materials are more, the dosage is larger, the main medicine occupation ratio is relatively lower, the tablet is larger, the weight of each tablet reaches 669mg, certain inconvenience is brought to the medication of patients, and the medication compliance of the patients is reduced; chinese patent publication No. CN114129524A discloses a paracetamol tablet and a preparation method thereof, wherein the tablet contains paracetamol, a binder, a disintegrating agent and a lubricant, and the preparation method comprises the steps of adopting the dry mixing of the paracetamol raw material, the binder and part of the disintegrating agent, adding water for granulating, adding the rest of the disintegrating agent after drying, The lubricant is prepared by granulating, tabletting after total mixing, and the preparation process has the following problems: the acetaminophen crystal belongs to brittle broken materials, has typical molar body compression characteristics, takes the shape of long needle crystals, has larger brittleness, weak plastic deformation capability and poor compressibility, adopts dry mixing of acetaminophen raw materials, adhesives and partial disintegrating agents, and has the problems of low adhesive consumption, possibly mixing uniformity in the dry mixing step, and the adoption of a water adding granulation process can not necessarily completely induce the adhesive property of the adhesives, so that the problems of cracking or cover falling and the like are easily generated in the subsequent tabletting process, and the quality of products is influenced. Therefore, although the prior art can solve the problems of poor material compressibility and inconsistent quality with the original grinding preparation in the preparation process of the acetaminophen tablet, the prescription composition is complex, the preparation process is not suitable for industrial production, the main medicine is relatively low, the tablet is large to cause trouble to patients in swallowing, or the ethanol solvent is used to cause solvent residue and the like, or the surfactant which does not accord with the simulation drug consistency evaluation BE exempt range is used.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention provides the acetaminophen tablet and the preparation method thereof, the prescription composition of the drug is simple, the types and the dosage of auxiliary materials are small, the main drug ratio is high, the tablet weight is small, the compliance of the patient in drug administration can be improved, the product quality is stable, the dissolution is complete, the quality is consistent with that of the original preparation, and the treatment effect of the acetaminophen tablet is ensured.
The invention provides a paracetamol tablet which comprises 86.88 parts by mass of paracetamol, 4.52 parts by mass of a binder, 2.90 parts by mass of a disintegrating agent, 5.21 parts by mass of a filling agent and 0.49 parts by mass of a lubricating agent.
Further, the adhesive is pregelatinized starch and povidone, and the weight ratio of the pregelatinized starch to povidone is 6:20.
Further, the disintegrating agent and the filler are pregelatinized starch.
Further, the lubricant is magnesium stearate.
The invention also provides a preparation method of the acetaminophen tablet, which comprises the following preparation steps:
S1, crushing acetaminophen;
s2, weighing acetaminophen and a filler for standby;
S3, drying the disintegrating agent for standby;
S4, uniformly stirring the adhesive and water to obtain mixed slurry for later use;
S5, adding the acetaminophen obtained in the step S2 and the filler into a wet granulator, stirring and mixing;
s6, adding the mixed slurry obtained in the step S4, stirring, and granulating to obtain wet granules;
S7, drying the wet particles;
s8, adding the disintegrating agent obtained in the step S3 into the dried granules, putting the granules into a mixer for total mixing, and adding a lubricant for total mixing;
And S9, tabletting the total mixed particles by a tablet press to obtain the acetaminophen tablet.
Further, the drying in the step S3 is to dry the disintegrating agent in a boiling granulator at 80-90 ℃ until the water content is 2-4%.
Further, the stirring in the step S4 is to weigh and stir the purified water and the pregelatinized starch uniformly to obtain pregelatinized starch slurry, to stir the purified water and the povidone uniformly to obtain povidone slurry, and to mix and stir the pregelatinized starch slurry and the povidone slurry uniformly to obtain mixed slurry.
Further, the granulating time in the step S6 is 30-60 seconds.
Further, the drying operation in the step S7 is to dry the granules to 1.8-2.8% of moisture at the inlet air temperature of 80 ℃.
Further, the total mixing time in the step S8 is 5min.
Compared with the prior art, the invention has the beneficial effects that:
1. The invention improves the prescription of the acetaminophen tablet, has simple prescription composition, less auxiliary materials and dosage, high main medicine occupation ratio and small tablet weight, can furthest reduce the management and inspection cost of the auxiliary materials, improves the compliance of the patient in medicine application, has stable product quality, is completely dissolved out, has the quality consistent with that of the original developer, does not contain a surfactant, and meets the requirement of evaluating BE exemption by imitating medicine consistency.
2. The preparation process of the acetaminophen tablet provided by the invention has the advantages of simple process, low production cost, safe production, no need of boiling water or organic solvent slurry preparation, high mechanical degree, suitability for industrial production and capability of solving the problem of poor compressibility of the acetaminophen tablet.
3. According to the invention, the conventional auxiliary materials are fully excavated, so that the pregelatinized starch plays four roles of a filler, an adhesive, a disintegrating agent and a stabilizer in the prescription, the water activity is reduced, and the pregelatinized starch dried to 2-4% of water content at 80-90 ℃ by a boiling granulator can re-adsorb trace water content remained in the acetaminophen tablet, so that the stabilizer plays a role and degradation is prevented.
4. The invention provides acetaminophen tablets and acetaminophen tablets (specification 0.5g, trade name)) Has the same in vitro dissolution behavior, the dissolution curve similarity factor f2 is more than 50, and the same therapeutic effect is achieved.
Detailed Description
The experimental methods of the present invention, in which specific conditions are not specified in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. The various common pharmaceutical excipients used in the examples are all commercial products.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The present invention will be further described in detail with reference to the following embodiments, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the description is only illustrative and is not intended to limit the scope of the invention. In addition, in the following description, descriptions of well-known structures and techniques are omitted so as not to unnecessarily obscure the present invention.
The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention.
EXAMPLE 1 paracetamol tablets of the invention and their preparation
The acetaminophen tablet formulations (1000 tablet dosage) of this example are shown in table 1 below:
TABLE 1 Paracetamol tablet recipe (1000 tablet dosage)
| Component (A) | Composition of the components | Dosage of | Content of |
| Main medicine | Acetaminophen | 500.0g | 86.88% |
| Filler (B) | Pregelatinized starch | 30.0g | 5.21% |
| Disintegrating agent | Pregelatinized starch | 16.7g | 2.90% |
| Adhesive agent | Pregelatinized starch | 6.0g | 1.04% |
| Adhesive agent | Povidone | 20.0g | 3.48% |
| Lubricant | Magnesium stearate | 2.8g | 0.49% |
The preparation method of the acetaminophen tablet comprises the following steps:
S1, crushing acetaminophen;
s2, weighing 500.0g of acetaminophen and 30.0g of pregelatinized starch for later use;
s3, placing 16.7g of pregelatinized starch into a boiling granulator, and drying at 80 ℃ until the water content is 4% for later use;
S4, weighing 54.0g of purified water, adding 6.0g of pregelatinized starch, and uniformly stirring to obtain pregelatinized starch slurry, taking 60.0g of purified water, adding 20.0g of povidone, and uniformly stirring to obtain povidone slurry, mixing the pregelatinized starch slurry and the povidone slurry uniformly to obtain 140.0g of mixed slurry for later use;
S5, adding the acetaminophen and the pregelatinized starch obtained in the step S2 into a wet granulator to stir at 180rpm and cut at 1800rpm, and mixing for 10min;
s6, adding the mixed slurry obtained in the step S4, stirring at 180rpm, cutting at 1800rpm, and granulating for 30 seconds to obtain wet granules;
S7, placing the wet granules in a boiling granulator, and drying the wet granules at an air inlet temperature of 80 ℃ until the moisture of the granules is 1.8%;
s8, adding the pregelatinized starch obtained in the step S3 into the dried particles, putting the mixture into a mixer and mixing for 5min, and adding 2.8g of magnesium stearate and mixing for 5min;
s9, tabletting the total mixed particles by a tabletting machine to obtain the acetaminophen tablet, wherein the tablet weight is 575.5mg.
EXAMPLE 2 paracetamol tablets of the invention and their preparation
The prescription of the paracetamol tablets (1 million tablet dosage) of this example is shown in table 2 below:
Table 2, prescription of Paracetamol tablet (1 ten thousand tablet dosage)
| Component (A) | Composition of the components | Dosage of | Content of |
| Main medicine | Acetaminophen | 5.00kg | 86.88% |
| Filler (B) | Pregelatinized starch | 0.3kg | 5.21% |
| Adhesive agent | Pregelatinized starch | 0.06kg | 1.04% |
| Disintegrating agent | Pregelatinized starch | 0.167kg | 2.90% |
| Adhesive agent | Povidone | 0.2kg | 3.48% |
| Lubricant | Magnesium stearate | 0.028kg | 0.49% |
The preparation method of the acetaminophen tablet comprises the following steps:
S1, crushing acetaminophen;
S2, weighing 5kg of acetaminophen and 0.3kg of pregelatinized starch for later use;
S3, placing 0.167kg of pregelatinized starch into a boiling granulator, and drying at 85 ℃ until the water content is 3% for later use;
S4, weighing 0.54kg of purified water, adding 0.06kg of pregelatinized starch, and uniformly stirring to obtain pregelatinized starch slurry, taking 0.6kg of purified water, adding 0.2kg of povidone, and uniformly stirring to obtain povidone slurry, mixing the pregelatinized starch slurry and the povidone slurry uniformly to obtain mixed slurry of 1.4kg for later use;
s5, adding the acetaminophen and the pregelatinized starch obtained in the step S2 into a wet granulator, stirring at 180rpm, cutting at 1800rpm, and mixing for 10min;
S6, adding 1.400kg of the mixed slurry obtained in the step S4, stirring at 180rpm, cutting at 1800rpm, and granulating for 45 seconds to obtain wet granules;
S7, placing the wet granules in a boiling granulator, and drying the wet granules at an air inlet temperature of 80 ℃ until the moisture of the granules is 2.3%;
s8, adding the dried particles into the pregelatinized starch obtained in the step S3, putting the pregelatinized starch into a mixer, mixing for 5min, and adding 0.028kg of magnesium stearate, mixing for 5min;
s9, tabletting the total mixed granules by a tablet press to obtain the acetaminophen tablet, wherein the tablet weight is 575.5mg.
EXAMPLE 3 paracetamol tablets of the invention and their preparation
The prescription of the paracetamol tablets (10 ten thousand tablet dosage) of this example is shown in table 3 below:
Table 3, prescription of Paracetamol tablet (10 ten thousand tablet dosage)
| Component (A) | Composition of the components | Dosage of | Content of |
| Main medicine | Acetaminophen | 50.00kg | 86.88% |
| Filler (B) | Pregelatinized starch | 3.00kg | 5.21% |
| Adhesive agent | Pregelatinized starch | 0.60kg | 1.04% |
| Disintegrating agent | Pregelatinized starch | 1.67kg | 2.90% |
| Adhesive agent | Povidone | 2.00kg | 3.48% |
| Lubricant | Magnesium stearate | 0.28kg | 0.49% |
The preparation method of the acetaminophen tablet comprises the following steps:
S1, crushing acetaminophen;
S2, weighing 50.00kg of acetaminophen and 3.00kg of pregelatinized starch for later use;
S3, placing 1.67kg of pregelatinized starch in a boiling granulator, and drying at 90 ℃ until the water content is 2% for later use;
S4, weighing 5.40kg of purified water, adding 0.60kg of pregelatinized starch, and uniformly stirring to obtain pregelatinized starch slurry, taking 6.00kg of purified water, adding 2.00kg of povidone, and uniformly stirring to obtain povidone slurry, mixing the pregelatinized starch slurry and the povidone slurry uniformly to obtain mixed slurry of 14.00kg for later use;
s5, adding the acetaminophen and the pregelatinized starch obtained in the step S2 into a wet granulator, stirring at 180rpm, cutting at 1800rpm, and mixing for 10min;
s6, adding 14.00kg of the mixed slurry obtained in the step S4, stirring at 180rpm, cutting at 1800rpm, and granulating for 60 seconds to obtain wet granules;
s7, placing the wet granules in a boiling granulator, and drying the wet granules at an air inlet temperature of 80 ℃ until the moisture of the granules is 2.8%;
S8, adding the dried particles into the pregelatinized starch obtained in the step S3, putting the pregelatinized starch into a mixer, mixing for 5min, and adding 0.28kg of magnesium stearate, mixing for 5min;
s9, tabletting the total mixed granules by a tablet press to obtain the acetaminophen tablet, wherein the tablet weight is 575.5mg.
Comparative example 1
The only difference between this comparative example and example 1 is that the disintegrant was not subjected to drying operation, i.e. the preparation process of the paracetamol tablet was:
S1, crushing acetaminophen;
S2, weighing 50.00kg of acetaminophen and 3.00kg of pregelatinized starch for later use;
S3, weighing 5.40kg of purified water, adding 0.60kg of pregelatinized starch, and uniformly stirring to obtain pregelatinized starch slurry, taking 6.00kg of purified water, adding 2.00kg of povidone, and uniformly stirring to obtain povidone slurry, mixing the pregelatinized starch slurry and the povidone slurry uniformly to obtain mixed slurry of 14.00kg for later use;
s4, adding the acetaminophen and the pregelatinized starch obtained in the step S2 into a wet granulator, stirring at 180rpm, cutting at 1800rpm, and mixing for 10min;
s5, adding 14.00kg of the mixed slurry obtained in the step S3, stirring at 180rpm, cutting at 1800rpm, and granulating for 30 seconds to obtain wet granules;
S6, placing the wet granules in a boiling granulator, and drying the wet granules at an air inlet temperature of 80 ℃ until the moisture of the granules is 1.8%;
s7, adding 1.67kg of pregelatinized starch into the dried particles, putting the mixture into a mixer for total mixing for 5min, and adding 0.28kg of magnesium stearate for total mixing for 5min;
S8, tabletting the total mixed granules by a tablet press to obtain the acetaminophen tablet, wherein the tablet weight is 575.5mg.
Comparative example 2
The only difference between the comparative example and the example 1 is that the step S4 in the preparation process is changed, the adhesive pregelatinized starch and povidone are not mixed together after being uniformly stirred with water respectively, but are directly mixed with water, namely, the step S4 is to weigh 114.0g of purified water, add 6.0g of pregelatinized starch and 20.0g of povidone, and uniformly stir to obtain 140.0g of mixed pulp for standby.
Comparative example 3
Act GlaxoSmithKline Consumer Healthcare, product of raw grinding agent paracetamol tablet with specification of 0.5g and trade name
Test example 1 dissolution investigation of acetaminophen tablet
1. Test samples p-acetaminophen tablets prepared in examples 1-3 and comparative examples 1-3;
2. Test method comprises detecting according to the first method of four general rules 0931 of Chinese pharmacopoeia of 2020 edition, wherein the dissolution medium is diluted hydrochloric acid solution (precise measurement of diluted hydrochloric acid 24mL and water to 1000 mL), and measuring the dissolution rates of acetaminophen tablets prepared in examples 1-3 and comparative examples 1-3 at 5min, 10min, 15min and 30 min;
3. the test results are shown in Table 4 below;
TABLE 4 dissolution values of Paracetamol tablets
As is clear from Table 4, the acetaminophen tablets prepared in examples 1-3 of the present invention were compared with the original grinding agent acetaminophen tablet (specification 0.5g, trade name) Has the same in-vitro dissolution behavior, the dissolution rate is more than 85% in 15min, and the acetaminophen tablet is a quick release preparation, the dissolution rate is more than 85% in 15min because the acetaminophen tablet is a imitative drug consistency evaluation BE exemption variety, the comparative dissolution profile similarity factor f2 is not required to demonstrate that the acetaminophen tablets prepared in examples 1-3 of the present invention have the same therapeutic effect as the acetaminophen tablet of the original drug manufactured by company GlaxoSmithKline Consumer Healthcare of comparative example 3. In comparative example 1, however, the dissolution rate was slow because the disintegrating agent was not dried in a boiling granulator at 80 to 90 ℃ until the water content was 2 to 4%, because the disintegrating ability of pregelatinized starch after drying was greatly enhanced, the dissolution rate of the preparation was improved, and the disintegrating ability of pregelatinized starch without drying in comparative example 1 was weak, and the dissolution rate was slow. In comparative example 2, the step S4 in the preparation process is changed, and the binder pregelatinized starch and povidone are not mixed with water after being uniformly stirred respectively, but are directly mixed with water, and although the dissolution rate of the prepared acetaminophen tablet is basically unchanged, the binder is difficult to dissolve and disperse completely by the method, so that the tablet is easy to generate 'splinter' during tabletting.
Test example 2 examination of the compression yield of acetaminophen tablets
1. Test samples p-acetaminophen tablets prepared in examples 1-3 and comparative examples 1-2;
2. The test method comprises calculating the qualification rate of the batch-produced tabletting according to the ratio of the qualified product output and the material receiving amount of the product;
3. Judging the standard that the surface is smooth, no splinter and loose is regarded as qualified;
4. test results:
TABLE 5 tabletting yield of paracetamol tablets
As is clear from Table 5, the paracetamol tablets prepared in examples 1-3 of the invention have smooth surfaces, no cracking and loosening phenomena, the tablet compression qualification rate reaches 100%, and the method for preparing the paracetamol tablets solves the problem of poor compressibility of the paracetamol tablets, has the advantages of simple process, low production cost, safe production and high degree of mechanization, is suitable for industrial production, and the tablet compression qualification rate of comparative example 1 also reaches 100%, but the dissolution rate is slow, because the disintegrating agent of comparative example 1 is not placed in a boiling granulator for drying at 80-90 ℃ until the water content is 2-4%, the pregelatinized starch without drying treatment has weaker disintegrating capability, which can lead to slow dissolution of the preparation, and the tablet compression qualification rate of the paracetamol tablets prepared in comparative example 2 is only 94.2%, because the preparation process of comparative example 2 is changed, the stability of the paracetamol tablets is affected, and the compressibility of the paracetamol tablets is poor.
Test example 3 stability investigation of acetaminophen tablet
1. Test samples p-acetaminophen tablets prepared in examples 1-3 and comparative examples 1-2;
2. The test method comprises placing in a stability test box at 40deg.C and 70%, taking out for 0 day, 1 month, 3 months and 6 months respectively, and measuring in vitro dissolution;
3. test results:
TABLE 6 stability investigation data for paracetamol tablets
| Group of | Day 0 | 1 Month | 3 Months of | 6 Months of |
| Example 1 | 100.2% | 99.6% | 99.7% | 99.8% |
| Example 2 | 99.9% | 99.7% | 99.8% | 99.7% |
| Example 3 | 99.7% | 99.4% | 99.6% | 99.5% |
| Comparative example 1 | 90.4% | 86.2% | 84.2% | 81.4% |
| Comparative example 2 | 99.3% | 99.2% | 99.1% | 99.0% |
As is clear from Table 6, the in vitro dissolution rates of the acetaminophen tablets prepared in examples 1-3 after being subjected to a high temperature and humidity environment of 40 ℃ and 70% for 1 month, 3 months and 6 months are all higher than those of the acetaminophen tablets prepared in comparative examples 1-3, and the in vitro dissolution rates of the acetaminophen tablets prepared in comparative example 1 are not significantly changed for 1 month, 3 months and 6 months, whereas the decrease trend of the in vitro dissolution rates of the acetaminophen tablets prepared in comparative example 1 is significant, because the disintegrant pregelatinized starch of comparative example 1 is not subjected to the operation of drying to water of 2-4% at 80-90 ℃ in a boiling granulator, and the pregelatinized starch after the drying operation has the effect of accelerating the disintegration rate of the acetaminophen tablets and improving the dissolution rates when used as a disintegrant, and the in vitro dissolution rate of comparative example 2 is not significantly decreased but the qualification rate of tabletting is lower.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (4)
1. The paracetamol tablet is characterized by comprising 86.88 parts by mass of paracetamol, 4.52 parts by mass of a binder, 2.90 parts by mass of a disintegrating agent, 5.21 parts by mass of a filler and 0.49 parts by mass of a lubricant;
the adhesive is pregelatinized starch and povidone, and the weight ratio of the pregelatinized starch to povidone is 6:20;
the disintegrating agent and the filler are pregelatinized starch;
The lubricant is magnesium stearate;
The preparation method of the paracetamol tablet comprises the following preparation steps:
S1, crushing acetaminophen;
s2, weighing acetaminophen and a filler for standby;
S3, drying the disintegrating agent for standby;
S4, uniformly stirring the adhesive and water to obtain mixed slurry for later use;
S5, adding the acetaminophen obtained in the step S2 and the filler into a wet granulator, stirring and mixing;
S6, adding the mixed slurry obtained in the step S4, stirring, and granulating to obtain wet granules;
S7, drying the wet particles;
s8, adding the dried particles into the disintegrating agent obtained in the step S3, putting the mixture into a mixer for total mixing, and adding a lubricant for total mixing;
S9, tabletting the total mixed particles by a tablet press to obtain acetaminophen tablets;
the drying in the step S3 is to dry the disintegrating agent in a boiling granulator at 80-90 ℃ until the water content is 2-4%;
the stirring in the step S4 is to uniformly stir the purified water and the pregelatinized starch to obtain pregelatinized starch slurry, uniformly stir the purified water and the povidone to obtain povidone slurry, and then uniformly mix and stir the pregelatinized starch slurry and the povidone slurry to obtain mixed slurry.
2. The method for preparing acetaminophen tablets of claim 1, wherein the granulating time in step S6 is 30-60 seconds.
3. The method for preparing acetaminophen tablets as claimed in claim 1, wherein the drying operation in step S7 is to dry to 1.8-2.8% of the granule moisture at 80 ℃.
4. The method for producing acetaminophen tablets as claimed in claim 1, wherein said total mixing time in step S8 is 5min.
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| CN105310990A (en) * | 2014-12-04 | 2016-02-10 | 蚌埠丰原涂山制药有限公司 | Sticking-resistant and cracking-resistant paracetamol tablet and preparation method thereof |
| CN108451916A (en) * | 2018-06-19 | 2018-08-28 | 重庆国泰康宁制药有限责任公司 | A kind of paracetamol drug combination preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105310990A (en) * | 2014-12-04 | 2016-02-10 | 蚌埠丰原涂山制药有限公司 | Sticking-resistant and cracking-resistant paracetamol tablet and preparation method thereof |
| CN108451916A (en) * | 2018-06-19 | 2018-08-28 | 重庆国泰康宁制药有限责任公司 | A kind of paracetamol drug combination preparation and preparation method thereof |
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