CN114306252A - Antipyretic analgesic and anti-inflammatory composition and preparation method thereof - Google Patents
Antipyretic analgesic and anti-inflammatory composition and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000000203 mixture Substances 0.000 title claims abstract description 16
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 8
- 239000003907 antipyretic analgesic agent Substances 0.000 title claims description 7
- 229960002373 loxoprofen Drugs 0.000 claims abstract description 52
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 claims abstract description 52
- 239000007919 dispersible tablet Substances 0.000 claims abstract description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 4
- 230000000202 analgesic effect Effects 0.000 claims abstract 3
- 230000001754 anti-pyretic effect Effects 0.000 claims abstract 3
- 239000002221 antipyretic Substances 0.000 claims abstract 3
- 229920002472 Starch Polymers 0.000 claims description 67
- 229940032147 starch Drugs 0.000 claims description 67
- 235000019698 starch Nutrition 0.000 claims description 67
- 239000008107 starch Substances 0.000 claims description 67
- 238000002156 mixing Methods 0.000 claims description 64
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 52
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 34
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 34
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 34
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 34
- 239000011734 sodium Substances 0.000 claims description 33
- 229910052708 sodium Inorganic materials 0.000 claims description 33
- 229940083542 sodium Drugs 0.000 claims description 33
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 32
- 238000007873 sieving Methods 0.000 claims description 30
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 26
- 229960004998 acesulfame potassium Drugs 0.000 claims description 26
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 26
- 239000000619 acesulfame-K Substances 0.000 claims description 26
- 235000019359 magnesium stearate Nutrition 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 239000008187 granular material Substances 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 23
- 238000007580 dry-mixing Methods 0.000 claims description 20
- 239000003826 tablet Substances 0.000 claims description 19
- 239000000463 material Substances 0.000 claims description 17
- 239000002245 particle Substances 0.000 claims description 16
- 235000015424 sodium Nutrition 0.000 claims description 13
- 239000002994 raw material Substances 0.000 claims description 12
- 239000002671 adjuvant Substances 0.000 claims description 10
- 238000004140 cleaning Methods 0.000 claims description 10
- 238000007599 discharging Methods 0.000 claims description 10
- 238000005469 granulation Methods 0.000 claims description 10
- 230000003179 granulation Effects 0.000 claims description 10
- 238000004806 packaging method and process Methods 0.000 claims description 10
- 238000007789 sealing Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000009835 boiling Methods 0.000 claims description 9
- 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 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 238000010981 drying operation Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 235000020985 whole grains Nutrition 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 238000012360 testing method Methods 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
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- 238000010521 absorption reaction Methods 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 238000011835 investigation Methods 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The invention relates to an antipyretic, analgesic and anti-inflammatory composition and a preparation method thereof, wherein the composition is a loxoprofen sodium dispersible tablet. The loxoprofen sodium has higher viscosity, and the dispersible tablets are easy to agglomerate and are not easy to completely pass through a No. 2 sieve after being disintegrated; the method combines hot nitrogen and fluidized bed to post-treat the dispersible tablet, thereby improving the stability of the dispersible tablet.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, relates to an antipyretic analgesic and anti-inflammatory dispersible tablet and a preparation method thereof, and more particularly relates to a loxoprofen sodium dispersible tablet and a preparation method thereof.
Background
Among 50 varieties sold in the world market in the leading market, Loxoprofen Sodium (Loxoprofen Sodium) is developed by three co-pending Co.Ltd, marketed in Japan in 7.1986 under the trade name of "Lesong", which is the first chemically synthesized propionic acid precursor non-steroidal anti-inflammatory drug (NSAIDs) in the world, and is metabolized in the body into a trans-OH type drug after oral administration to inhibit the biosynthesis of prostaglandin.
Loxoprofen sodium with the chemical name of 2- [4- (2-oxocyclopentane-1-ylmethyl) phenyl]Sodium propionate of formula C15H17NaO3The chemical structure is as follows:
at present, loxoprofen sodium preparations in domestic markets mainly comprise tablets and capsules and have the defects of slow dissolution, low bioavailability and the like. Is difficult to be taken by the old, children, apoplexy patients and patients with swallowing difficulty. The dispersible tablet has the advantages of convenient administration, rapid disintegration, rapid absorption, and high bioavailability. Combines the advantages of the tablet and the liquid preparation and avoids the disadvantages of the tablet and the liquid preparation, is a preparation form which effectively improves the bioavailability of the medicament which is insoluble in water and has low bioavailability, and simultaneously keeps the characteristics of convenient carrying and good stability of the tablet.
The loxoprofen sodium dispersible tablet belongs to a medicine which is in short of clinical urgent need. The loxoprofen sodium has higher viscosity, so that the dispersible tablet composition is easy to agglomerate after being disintegrated and is not easy to completely pass through a No. 2 sieve; secondly, the tablet is easy to absorb moisture, the tablet after absorbing moisture is fluffy, and the content of the main drug is reduced, especially the dissolution rate is obviously reduced.
The technical problem solved by the invention is as follows: (1) the dispersion uniformity of the loxoprofen sodium is improved by regulating and controlling the dosage proportion by taking the low-substituted hydroxypropyl cellulose as an internal disintegrating agent and taking the sodium carboxymethyl starch, the microcrystalline cellulose and the starch as a combined external disintegrating agent; (2) the dispersible tablet is post-treated by combining hot nitrogen and a fluidized bed, so that the stability of the dispersible tablet is improved.
Disclosure of Invention
The invention aims to provide a loxoprofen sodium dispersible tablet and a preparation method thereof.
The invention aims to solve the problems by adopting the following technical scheme:
the composition is characterized in that a unit dose of the composition contains 60mg of loxoprofen sodium, 199-207 mg of starch, microcrystalline cellulose and carboxymethyl starch sodium, 110-130 mg of low-substituted hydroxypropyl cellulose, 5mg of acesulfame potassium and 1mg of magnesium stearate, wherein the composition is a dispersible tablet, the low-substituted hydroxypropyl cellulose is used as an internal disintegrating agent, and the carboxymethyl starch sodium, the microcrystalline cellulose and the starch are used as combined external disintegrating agents.
The composition is characterized in that each 1000 tablets contain 60g of loxoprofen sodium, 165-255 g of starch, microcrystalline cellulose and sodium carboxymethyl starch, 110-130 g of low-substituted hydroxypropyl cellulose, 5g of acesulfame potassium, 1g of magnesium stearate and 25mL of ethanol. Wherein, the low-substituted hydroxypropyl cellulose is used as an internal disintegrating agent, and the sodium carboxymethyl starch, the microcrystalline cellulose and the starch are used as combined external disintegrating agents. The preparation method comprises the following steps:
1) preparing raw materials and auxiliary materials: weighing loxoprofen sodium, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, acesulfame potassium, carboxymethyl starch sodium and magnesium stearate according to the prescription amount; wherein the loxoprofen sodium is crushed and sieved by a 200-230-mesh sieve; sieving the low-substituted hydroxypropyl cellulose by a sieve of 100-120 meshes; mixing and crushing starch, microcrystalline cellulose and sodium carboxymethyl starch, sieving with a sieve of 80-100 meshes, crushing acesulfame potassium and magnesium stearate, and sieving with a sieve of 70-80 meshes;
2) mixing and granulating: adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 10-20 minutes; after dry mixing, adding ethanol, and wet mixing for 10-15 min to prepare wet particles; drying, stopping, cleaning a filter bag, discharging and preparing dry particles;
3) and (3) total mixing of whole grains: adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step 1) and a disintegrating agent, mixing for 30-35 min, and finally adding magnesium stearate and mixing for 15 min;
4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
The preparation method of the antipyretic analgesic anti-inflammatory dispersible tablet is characterized in that the drying operation in the step 2) is to dry wet granules in a nitrogen boiling dryer for 8-10 min;
a preparation method of an antipyretic analgesic and anti-inflammatory drug dispersible tablet is characterized in that the nitrogen flow rate is controlled to be 12-15 m/s, and the temperature is controlled to be 40-50 ℃.
The preparation method of the antipyretic analgesic anti-inflammatory dispersible tablet is characterized in that in the step 3), the mass ratio of sodium carboxymethyl starch, starch and microcrystalline cellulose in the combined disintegrating agent is 0.3:1.2: 1-0.4: 1.2: 1.
The invention has the advantages and positive effects that:
(1) according to the technical scheme provided by the invention, the low-substituted hydroxypropyl cellulose is used as an internal disintegrating agent, the sodium carboxymethyl starch, the microcrystalline cellulose and the starch are used as combined external disintegrating agents, the product is rapidly disintegrated by regulating and controlling the dosage proportion, and the dispersion uniformity of the product is improved.
(2) According to the technical scheme provided by the invention, the dispersing tablet is treated in a mode of combining hot nitrogen and a fluidized bed, and the stability of the dispersing tablet is improved by controlling the flow rate and the temperature of the nitrogen.
(3) The technical scheme provided by the invention has the advantages of simple preparation process and convenience in operation, improves the dispersion uniformity of the medicine, and is suitable for industrial mass production.
Detailed Description
The advantageous effects of the present invention will now be further described by the following examples, which are for illustrative purposes only and do not limit the scope of the present invention, and variations and modifications apparent to those skilled in the art to which the present invention pertains are also included in the scope of the present invention. The technical contents not described in detail in the present invention are all known techniques.
Example 1:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 80-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 13m/s, the temperature is controlled at 45 ℃) to dry for 9min, stopping the machine, cleaning a filter bag, discharging materials and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Example 2:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, pulverizing, sieving with 100 mesh sieve, pulverizing acesulfame potassium and magnesium stearate, and sieving with 80 mesh sieve;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 20 min; adding ethanol after dry mixing, and wet mixing for 15min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 15m/s, the temperature is controlled at 45 ℃) to dry for 10min, stopping the machine, cleaning a filter bag, discharging materials, and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 35min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Example 3:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 80-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 10 minutes; adding ethanol after dry mixing, and wet mixing for 10min to obtain wet granules; transferring the wet granules into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 10m/s, the temperature is controlled at 40 ℃) to dry for 8min, stopping the machine, cleaning filter bags, discharging the materials to prepare dry granules;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Comparative example 1:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 13m/s, the temperature is controlled at 45 ℃) to dry for 9min, stopping the machine, cleaning a filter bag, discharging materials and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Comparative example 2:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 13m/s, the temperature is controlled at 45 ℃) to dry for 9min, stopping the machine, cleaning a filter bag, discharging materials and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the starch treated in the step (1) and the microcrystalline cellulose, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Comparative example 3:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 13m/s, the temperature is controlled at 45 ℃) to dry for 9min, stopping the machine, cleaning a filter bag, discharging materials and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Comparative example 4:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; transferring the wet particles into a nitrogen boiling dryer (the nitrogen flow rate is controlled at 13m/s, the temperature is controlled at 45 ℃) to dry for 9min, stopping the machine, cleaning a filter bag, discharging materials and preparing dry particles;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
Comparative example 5:
a loxoprofen sodium dispersible tablet is prepared from the following raw and auxiliary materials by weight in 1000 tablets:
the preparation method comprises the following steps:
(1) the loxoprofen sodium is crushed and sieved by a 100-mesh sieve; sieving low-substituted hydroxypropyl cellulose with 100-mesh sieve; mixing starch, microcrystalline cellulose and sodium carboxymethyl starch, crushing, sieving with a 80-mesh sieve, crushing acesulfame potassium and magnesium stearate, and sieving with a 80-mesh sieve for later use;
(2) adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 15 min; adding ethanol after dry mixing, and wet mixing for 12min to obtain wet granules; drying wet granules at 60 deg.C for 20min by air blast, stopping machine, cleaning filter bag, discharging to obtain dry granules;
(3) adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step (1) and a disintegrating agent, mixing for 30min, and finally adding magnesium stearate and mixing for 15 min;
(4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
The invention also provides the following experimental examples to further illustrate the product of the invention:
experimental example 1 Dispersion uniformity test of loxoprofen sodium dispersible tablets of the present invention
The dispersible tablet inspection method comprises the following steps: 2 test samples are taken and put into a 100mL beaker, 100mL of water with the temperature of 20 +/-1 ℃ is added, the mixture is shaken for 3 minutes, and the mixture is completely disintegrated and passes through a No. 2 sieve.
Table 1 dispersion uniformity test data
The test data shows that: the dispersible tablets of the examples pass through the No. 2 sieve within 0.6min, the dispersible tablets of the control examples pass through the No. 2 sieve within 1.0-3.2 min, and the commercially available dispersible tablets pass through the No. 2 sieve within 1.8 min. Namely, the dispersing effect of the dispersible tablet of the invention is better than that of the comparative example and the commercially available dispersible tablets.
Experimental example 2 stability test of loxoprofen sodium dispersible tablet of the present invention
(1) Test for influencing factor
High temperature test the loxoprofen sodium dispersible tablet obtained in example 1 of the present invention was taken, placed in a sealed clean container with an opening, left at 60 ℃ for 10 days, sampled on days 5 and 10, and examined according to the focus of stability examination.
The loxoprofen sodium dispersible tablet obtained in example 1 of the present invention is taken in a high humidity test, and the tablet is placed in a constant humidity clean container (relative humidity 90% +/-5%) after being opened, and is sampled on the 5 th day and the 10 th day, and the detection is carried out according to the stability focus item.
The loxoprofen sodium dispersible tablet obtained in example 1 of the present invention was taken out in the light box, placed for 10 days under 4500LX conditions after opening, sampled on days 5 and 10, and examined according to the stability focus examination item.
The effect test results are shown in the following table:
TABLE 2 loxoprofen sodium dispersible tablet influence factor test results
(2) And (3) long-term test stability investigation:
the dispersible tablets prepared in examples 1 to 3 and comparative examples 1 to 5 and commercially available dispersible tablets were stored in the same package at 25 ℃ for 12 months under natural conditions, and examined for their properties, dissolution rates, related substances and contents at 0, 3, 6, 9 and 12 months, respectively. The related substances and contents were measured by HPLC, and the results are shown in Table 3.
TABLE 3 stability test results of loxoprofen sodium dispersible tablet of the present invention in accelerated test
As shown in Table 3, the appearance and the content of the sample in each test were not substantially changed during the long-term stability test. However, the dissolution rates of the dispersible tablets prepared in the comparative example and the dispersible tablets sold in the market are obviously reduced, and related substances are obviously increased; the dissolution of the dispersible tablet of the invention is basically unchanged, and the increase of related substances is much smaller, which shows that the invention can improve the dispersion uniformity and stability of the dispersible tablet by controlling the mixture ratio and carrying out post-treatment on the dispersible tablet by adopting a mode of combining hot nitrogen and a fluidized bed.
Claims (5)
1. The composition is characterized in that a unit dose of the composition contains 60mg of loxoprofen sodium, 165-255 mg of starch, microcrystalline cellulose and sodium carboxymethyl starch, 110-130 mg of low-substituted hydroxypropyl cellulose, 5mg of acesulfame potassium and 1mg of magnesium stearate, wherein the composition is a dispersible tablet, the low-substituted hydroxypropyl cellulose is used as an internal disintegrating agent, and the sodium carboxymethyl starch, the microcrystalline cellulose and the starch are used as combined external disintegrating agents.
2. The composition is characterized in that each 1000 tablets contain 60g of loxoprofen sodium, 165-255 g of starch, microcrystalline cellulose and sodium carboxymethyl starch, 110-130 g of low-substituted hydroxypropyl cellulose, 5g of acesulfame potassium, 1g of magnesium stearate and 25mL of ethanol. Wherein, the low-substituted hydroxypropyl cellulose is used as an internal disintegrating agent, and the sodium carboxymethyl starch, the microcrystalline cellulose and the starch are used as combined external disintegrating agents. The preparation method comprises the following steps:
1) preparing raw materials and auxiliary materials: weighing loxoprofen sodium, starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, acesulfame potassium, carboxymethyl starch sodium and magnesium stearate according to the prescription amount; wherein the loxoprofen sodium is crushed and sieved by a sieve of 80-100 meshes; sieving the low-substituted hydroxypropyl cellulose by a sieve of 80-100 meshes; mixing and crushing starch, microcrystalline cellulose and sodium carboxymethyl starch, sieving with a sieve of 80-100 meshes, crushing acesulfame potassium and magnesium stearate, and sieving with a sieve of 80 meshes;
2) mixing and granulating: adding the loxoprofen sodium, the acesulfame potassium and the low-substituted hydroxypropyl cellulose prepared in the step (1) into a high-speed mixing granulator, and sealing, stirring and dry-mixing for 10-20 minutes; after the dry mixing is finished, adding ethanol for wet mixing for 10-15 min to prepare wet particles; drying, stopping, cleaning a filter bag, discharging and preparing dry particles;
3) and (3) total mixing of whole grains: adding the dry granules prepared in the previous step into a granulator for granulation, adding the sodium carboxymethyl starch, the starch and the microcrystalline cellulose treated in the step 1) and a disintegrating agent, mixing for 30-35 min, and finally adding magnesium stearate and mixing for 15 min;
4) tabletting: mixing the raw materials and adjuvants uniformly, tabletting, inspecting, and packaging.
3. The method for preparing the dispersible tablet with antipyretic, analgesic and anti-inflammatory effects as claimed in claim 2, wherein the drying operation in step 2) is to dry the wet granules in a nitrogen boiling dryer for 17-20 min.
4. The preparation method of the dispersible tablet of antipyretic analgesic and anti-inflammatory agent as claimed in claim 3, characterized in that the nitrogen flow rate is controlled at 12-15 m/s and the temperature is controlled at 40-50 ℃.
5. The preparation method of the dispersible tablet with antipyretic, analgesic and anti-inflammatory effects as claimed in claim 2, wherein the mass ratio of sodium carboxymethyl starch, starch and microcrystalline cellulose in the combined disintegrating agent in step 3) is 0.3:1.2: 1-0.4: 1.2: 1.
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Application publication date: 20220412 |