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CN115300468B - Pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet and preparation method thereof - Google Patents

Pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet and preparation method thereof Download PDF

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Publication number
CN115300468B
CN115300468B CN202210942080.7A CN202210942080A CN115300468B CN 115300468 B CN115300468 B CN 115300468B CN 202210942080 A CN202210942080 A CN 202210942080A CN 115300468 B CN115300468 B CN 115300468B
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parts
orally disintegrating
disintegrating tablet
paracetamol
pediatric paracetamol
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CN115300468A (en
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管悦琴
孙盛华
王秀兰
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Jiuhua Huayuan Pharmaceutical Co ltd
Jiuhua Huayuan Pharmaceutical Guilin Co ltd
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Guangxi Chunzhengtang Pharmaceutical Co ltd
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    • 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
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37—Digestive system
    • A61K35/413—Gall bladder; Bile
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system

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Abstract

The invention discloses an pediatric paracetamol, chlorphenamine maleate and preparation method thereof, wherein the orally disintegrating tablet comprises the following raw materials in parts by weight: 1250 parts of acetaminophen, 5 parts of chlorpheniramine maleate, 50 parts of artificial bezoar, 500200-2000 parts of mannitol cross-polymerization co-processed material, 100-1000 parts of low-substituted hydroxypropyl cellulose L-2188-880 parts, 12-120 parts of coating material, 17-170 parts of flavoring agent, 24-240 parts of adhesive, 9-90 parts of lubricant, 3-30 parts of coating plasticizer and 2-20 parts of pH regulator. The orally disintegrating tablet can be rapidly disintegrated in 1 minute under the condition of no water and little saliva or little water, active ingredients are released in the oral cavity, and partial active ingredients can be directly absorbed into blood through oral mucosa, so that the bioavailability is greatly reduced due to the fact that partial active ingredients are damaged caused by the first pass effect of liver absorbed by gastrointestinal tracts is avoided.

Description

Pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet and preparation method thereof
Technical Field
The invention relates to the technical field of orally disintegrating tablets, in particular to an orally disintegrating tablet of pediatric paracetamol and chlorphenamine maleate and a preparation method thereof.
Background
The existing pediatric paracetamol, which is taken by drinking water, is required to be swallowed by the child, and the poor medication compliance of the child is common in view of the poor medication compliance of the child, particularly the difficulty in swallowing after the child has a cold, and the taking of the tablet is also caused to be very difficult.
The orally disintegrating drug delivery system is a new dosage form which is rapidly developed in the field of pharmaceutical preparations in recent years, the preparation does not need water or only needs a small amount of water, chewing is not needed, the tablet is placed on the tongue surface and is rapidly dissolved or disintegrated and released when meeting saliva, and the tablet is rapidly absorbed into blood through oral mucosa; partially or by swallowing power into the stomach.
In view of the foregoing, there is a need to develop an orally disintegrating tablet of pediatric paracetamol, which solves the problem of difficult administration of pediatric paracetamol, and pediatric paracetamol.
Disclosure of Invention
Based on the technical problems existing in the background technology, the invention provides the pediatric paracetamol and chlorphenamine maleate orally disintegrating tablet and the preparation method thereof, the orally disintegrating tablet can be rapidly disintegrated in 1 minute under the condition of no water and little saliva or little water, active ingredients can be released in the oral cavity, part of the active ingredients can be directly absorbed into blood through oral mucosa, the bioavailability is greatly reduced because part of the active ingredients are damaged due to the first pass effect of liver absorbed by gastrointestinal tract is avoided, and various toxicity and adverse reactions caused by liver metabolites are avoided.
The pediatric paracetamol, the invention provides an orally disintegrating tablet which comprises the following raw materials in parts by weight:
1250 parts of acetaminophen, 5 parts of chlorpheniramine maleate, 50 parts of artificial bezoar, 500 200 to 2000 parts of mannitol cross-polymerization copolymer Mount common treatment substance, 88 to 880 parts of low-substituted hydroxypropyl cellulose L-21, 100 to 1000 parts of microcrystalline cellulose, 12 to 120 parts of coating material, 17 to 170 parts of flavoring agent, 24 to 240 parts of adhesive, 9 to 90 parts of lubricant, 3 to 30 parts of coating plasticizer, and 2 to 20 parts of pH regulator and effervescent agent.
Preferably, the binder is one or more of povidone, hydroxypropyl cellulose, hypromellose, hydroxymethyl cellulose, hydroxyethyl methylcellulose, carboxymethyl ethylcellulose, methylcellulose, ethylcellulose, methylethyl cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellulose propionate, hypromellose phthalate, hypromellose acetate succinate, hydroxypropyl methylcellulose acetate trimellitate, ethylhydroxyethyl cellulose, vinyl acetate povidone polymer matrix, sodium polyacrylate, polyoxyethylene (160) polyoxypropylene (30) glycol, polyethylene oxide, pullulan, polyvinyl alcohol, polyvinyl acetate, glyceryl, polyacrylamide, polyacrylic acid resin No. ii, polyacrylic acid resin No. iii, methyl vinyl ether/maleic anhydride copolymer, carbomer, copolyvidone, copolymer of ethyl acrylic acid or methacrylic acid.
Preferably, the lubricant is one or more of sodium stearyl fumarate, sodium stearate, stearic acid, glyceryl palmitostearate and zinc stearate.
Preferably, the coating material is one or more of Uttky E12.5, ethyl cellulose, uttky E30, polyacrylic resin II, polyacrylic resin III, methyl vinyl ether/maleic anhydride copolymer and hydroxypropyl methylcellulose phthalate.
Preferably, the coating plasticizer is one or more of dibutyl sebacate, dibutyl phthalate, diethyl phthalate, triethyl citrate and dimethyl phthalate.
Preferably, the pH regulator and the effervescent agent are one or more of sodium bicarbonate, sodium carbonate, magnesium carbonate and basic magnesium carbonate.
Preferably, the flavoring agent is one or more of citric acid, sucralose, aspartame, acesulfame potassium, citric acid and arabinose.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate and the orally disintegrating tablet provided by the invention comprises the following steps:
s1: uniformly mixing an adhesive, a flavoring agent and chlorpheniramine maleate in an ethanol solution to prepare an adhesive solution for later use;
s2: adding a coating plasticizer into the coating material and uniformly mixing to obtain a coating liquid;
S3: mixing artificial bezoar, 5-15% low substituted hydroxypropyl cellulose L-21 and 5-15% mannitol cross-polymerization copolymer Maishan co-processed product 500 uniformly, adding 1-10% binder solution in S1 to prepare soft material, granulating with screen, drying, and finishing with screen;
s4: placing the material subjected to the finishing of the step S3 into a coating machine, spraying coating liquid in the step S2, and fully drying layer by layer to obtain pellets;
s5: adding 50-60% of low-substituted hydroxypropyl cellulose L-21 and 85-95% of mannitol cross-polymerization copolymerization Mount common processed substance 500 and microcrystalline cellulose into acetaminophen, uniformly mixing, adding the rest binder in S1, preparing into soft material, granulating, drying and finishing to obtain pediatric paracetamol orally disintegrating tablet particles;
s6: and (3) adding the pellets prepared in the step (S4), a lubricant, a pH regulator and the balance of low-substituted hydroxypropyl cellulose L-21 into the pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet granules in the step (S5), uniformly mixing, and tabletting to prepare the pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet.
Preferably, the working parameters of the coating machine in S4 are as follows: the rotating speed of the coating machine is controlled to be 2-3r/min, the air inlet temperature is 60-70 ℃ and is preheated to the air outlet temperature of 40-45 ℃, and then the rotating speed of the coating machine is adjusted to be 7-9r/min and the air inlet temperature is 60-70 ℃.
Preferably, the drying conditions in S3 and S5 are: boiling and drying at 70-80deg.C until the water content of the material is 2.5-3.2%.
The beneficial technical effects of the invention are as follows:
(1) The invention adjusts the prescription of the prior art, namely pediatric paracetamol, chlorphenamine maleate granules or tablets, adds novel auxiliary materials, adopts a novel preparation technology, utilizes the physical and chemical properties of the novel auxiliary materials, develops a novel preparation orally disintegrating tablet with rapid onset and high bioavailability aiming at the physicochemical properties of main active ingredients of paracetamol, artificial bezoar and chlorpheniramine maleate, is convenient for children to take, improves the compliance of children to take medicine, covers the strong bitter taste of the artificial bezoar to improve the taste, and independently prepares the oral cavity capsule into pellets to release and absorb the oral cavity, thereby avoiding the remarkable reduction of compliance of children to take medicine due to the generation of strong bitter taste in the oral cavity.
(2) The pediatric paracetamol, the pharmaceutical composition and the orally disintegrating tablet prepared by the invention can be rapidly disintegrated within 1 minute under the condition of no water and little saliva or little water, active ingredients can be released in the oral cavity, and part of the active ingredients can be directly absorbed into blood through oral mucosa, so that the bioavailability is greatly reduced due to the destruction of part of active ingredients caused by the first pass effect of liver absorbed by gastrointestinal tracts, and various toxicity and adverse reactions caused by liver metabolites are avoided.
(3) The pH regulator such as sodium bicarbonate can increase the solubility and release rate of acetaminophen, chlorpheniramine maleate and artificial bezoar, and the sodium bicarbonate can generate carbon dioxide bubbles when being dissolved in water and meet citric acid, so that the gritty feeling of the orally disintegrating tablet caused by rapid disintegration is reduced.
(4) The disintegrating agent consists of mannitol cross-polymerization and copolymerization Maishan co-processed matter 500, low-substituted hydroxypropyl cellulose L-21 and microcrystalline cellulose, and through mutual synergistic promotion, index parameters such as disintegration time limit, water absorption rate, dissolution rate of paracetamol and chlorpheniramine maleate, bioavailability and the like of the pediatric paracetamol and chlorpheniramine maleate orally disintegrating tablet are obviously improved.
Detailed Description
Example 1
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 21-44 g of low-substituted hydroxypropyl cellulose, 50g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 24g low substituted hydroxypropyl cellulose L-21, 90g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 16g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Example 2
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500.6 g of mannitol cross-polymerization and copolymerization Mount common processed product, 30 g of povidone K, 7g of citric acid, 8.8g of low-substituted hydroxypropyl cellulose L-21, 67.6g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 0.8g of low-substituted hydroxypropyl cellulose L-21 and 13.2g of mannitol cross-polymerization and copolymerization Maishan co-processed product 500 into the fine powder of the artificial bezoar with the prescription amount, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 4.8g low substituted hydroxypropyl cellulose L-21, 104.4g mannitol cross-polymerization and copolymerization Maishan co-processed product 500, microcrystalline cellulose, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve, granulating, boiling at 75deg.C until water content is 3%, and granulating with 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 3.2g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and 9.5mm to prepare tablets.
Example 3
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500.78 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 88g of low-substituted hydroxypropyl cellulose L-21, 28g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 8g of low-substituted hydroxypropyl cellulose L-21 and 6g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 48g low substituted hydroxypropyl cellulose L-21, 72g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 32g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Example 4
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 21 g of low-substituted hydroxypropyl cellulose L-84 g, 90g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 12g of low-substituted hydroxypropyl cellulose L-21 and 2g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 43.2g low-substituted hydroxypropyl cellulose L-21 and 18g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, preparing into soft material, preparing into wet granules by 20 mesh nylon sieve, boiling and drying at 75deg.C until water content is about 3%, and granulating by 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 28.8g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and 9.5mm to prepare tablets.
Example 5
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
S1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 14g of mannitol cross-polymerization and copolymerization Maishan co-processed product 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 180g mannitol cross-polymerized and copolymerized Maishan co-processed product 500, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, making into wet granule with 20 mesh nylon sieve, boiling and drying at 75deg.C until water content is about 3%, and finishing granule with 16 mesh nylon sieve to obtain sugar-free pediatric acetaminophen xanthona-sensitive orally disintegrating tablet granule;
s4: and (3) taking the particles prepared in the step (S3), adding sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to obtain tablets.
Example 6
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 21 g of low-substituted hydroxypropyl cellulose L-64 g, 10g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
S1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 36g low substituted hydroxypropyl cellulose L-21, 110g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 24g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Example 7
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 19g of low-substituted hydroxypropyl cellulose L-21, 100g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 9g low substituted hydroxypropyl cellulose L-21, 65g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 6g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Example 8
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500.2 g of mannitol cross-polymerization and copolymerization Mount common treatment product, 2.4g of povidone K, 7g of citric acid, 47.2g of low-substituted hydroxypropyl cellulose L-21, 53.2g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, and adding 50% ethanol solution to 240ml to prepare 1% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 25.9g low substituted hydroxypropyl cellulose L-21, 93.2g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, and sieving with 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 17.3g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and 9.5mm to prepare tablets.
Example 9
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 21 g of low-substituted hydroxypropyl cellulose, 46g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate orally disintegrating tablet provided by the embodiment comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 10% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 27.6g low-substituted hydroxypropyl cellulose L-21, 86g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, preparing into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is about 3%, and sieving with 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 8.4g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and 9.5mm to prepare tablets.
Comparative example 1
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 72g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following steps:
S1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 14g of mannitol cross-polymerization and copolymerization Maishan co-processed product 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 108g mannitol cross-polymerized and copolymerized Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest binder solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: and (3) taking the particles prepared in the step (S3), adding sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to obtain tablets.
Comparative example 2
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 30 g of povidone K, 7g of citric acid, 21 g of low-substituted hydroxypropyl cellulose, 100g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following steps:
s1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 14g of low-substituted hydroxypropyl cellulose L-21 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 48g low substituted hydroxypropyl cellulose L-21 and microcrystalline cellulose, mixing, adding 225ml of the rest binder solution prepared in S1, mixing, making into soft material, sieving with 20 mesh nylon sieve, granulating, boiling at 75deg.C, drying until water content is 3%, and sieving with 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 32g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Comparative example 3
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization copolymer Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 21-69 g of low-substituted hydroxypropyl cellulose L, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following steps:
S1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 41g low substituted hydroxypropyl cellulose L-21 and 115g mannitol cross-polymerization and copolymerization Maishan co-processed product 500, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol and chlorphenamine maleate orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 24g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Comparative example 4
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization and copolymerization Maishan co-processed product, 30 g of povidone K, 7g of citric acid, 45g of low-substituted hydroxypropyl cellulose L-21, 50g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following steps:
S1: adhesive preparation
Taking the prescription amount of povidone K30, uniformly mixing the povidone K30 with the prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and preparing 5% povidone K30 adhesive solution containing the prescription amount of chlorpheniramine maleate, sucralose and citric acid for later use.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 25g low substituted hydroxypropyl cellulose L-21, 90g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, making into soft material, sieving with 20 mesh nylon sieve to obtain wet granule, boiling and drying at 75deg.C until water content is 3%, sieving with 16 mesh nylon sieve, and granulating to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 16g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and the thickness of 9.5mm to prepare tablets.
Comparative example 5
The pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 12.5 g of Uttky E, 500 g of mannitol cross-polymerization copolymerization Maishan co-processed product, 7g of citric acid, 21-48 g of low-substituted hydroxypropyl cellulose, 54g of microcrystalline cellulose, 1.5g of sucralose, 1.5g of diethyl phthalate, 1g of sodium bicarbonate and 4.5g of sodium stearyl fumarate.
The preparation method of the pediatric paracetamol, the chlorphenamine maleate orally disintegrating tablet provided by the comparative example comprises the following steps:
S1: adhesive preparation
Mixing prescription amount of citric acid, chlorpheniramine maleate and sucralose, adding 50% ethanol solution to 240ml, and making into adhesive solution containing prescription amount of chlorpheniramine maleate, sucralose and citric acid.
S2: preparation of artificial bezoar micropill
S21: and adding the Uttky E12.5 into diethyl phthalate, and uniformly mixing, namely uniformly dispersing the diethyl phthalate into the Uttky E12.5 solution and completely dissolving to obtain the coating liquid.
S22: pulverizing calculus bovis into 120 mesh fine powder;
s23: adding 4g of low-substituted hydroxypropyl cellulose L-21 and 10g of mannitol cross-polymerization and copolymerization Maishan co-processed substance 500 into the prescription amount of artificial bezoar fine powder, uniformly mixing, adding 15ml of the adhesive solution prepared in the step S1 to prepare a soft material, granulating by using a 30-mesh stainless steel screen, boiling and drying at 75 ℃ until the water content is about 3%, and finishing the granules by using a 20-mesh stainless steel screen for later use.
S24: placing artificial bezoar particles in a coating machine, controlling the rotating speed of the coating machine to be 3 revolutions per minute, preheating the air inlet temperature to be 65 ℃ to the air outlet temperature to be 42 ℃ for 30 minutes, adjusting the rotating speed of the coating machine to be 8 revolutions per minute, spraying coating liquid prepared by S21 which is 1.5 times of the quantity of the artificial bezoar particles into the coating machine, and fully drying the coating liquid layer by layer to obtain the artificial bezoar pellets for later use.
S3: pulverizing acetaminophen into 120 mesh fine powder, adding 26.4g low-substituted hydroxypropyl cellulose L-21, 94g mannitol cross-polymerization and copolymerization Maishan co-processed product 500 and microcrystalline cellulose, mixing uniformly, adding 225ml of the rest adhesive solution prepared in S1, mixing uniformly, preparing into soft material, preparing into wet granules by 20 mesh nylon sieve, boiling and drying at 75deg.C until water content is about 3%, and granulating by 16 mesh nylon sieve to obtain sugar-free pediatric paracetamol orally disintegrating tablet granule;
s4: taking the particles prepared in the step S3, adding 17.6g of low-substituted hydroxypropyl cellulose, sodium bicarbonate, sodium stearyl fumarate and artificial bezoar pellets, uniformly mixing, and flatly stamping at the pressure of 6kg and 9.5mm to prepare tablets.
Comparative example 6
The comparative example takes the existing pediatric paracetamol granules as an example, and comprises the following raw materials in parts by weight:
125g of acetaminophen, 0.5g of chlorpheniramine maleate, 5g of artificial bezoar, 5872 parts of sucrose and 1500ml of ethanol.
The preparation method of the pediatric paracetamol, the paracetamol and the chlorphenamine maleate granules provided by the comparative example comprises the following steps:
s1: pulverizing artificial bezoar and acetaminophen into 120 mesh fine powder;
s2: dissolving chlorpheniramine maleate in ethanol to obtain ethanol solution of chlorpheniramine maleate;
S3: mixing the prescription amount of artificial bezoar fine powder with acetaminophen uniformly by adopting an equivalent incremental method, adding the prescription amount of sucrose in the same way, mixing uniformly, adding chlorpheniramine maleate ethanol solution, mixing uniformly, preparing 16-mesh wet granules, boiling and drying at 75 ℃ until the water content is about 3%, and sieving with a 14-mesh sieve to obtain the pediatric paracetamol granules.
The quality index of pediatric paracetamol, orally disintegrating tablets/granules prepared in examples 1-9 and comparative examples 1-6 was tested, wherein:
(1) The method for measuring the content of acetaminophen comprises the following steps:
a) Sample solution preparation: taking 60g of a sample, precisely weighing, uniformly mixing, grinding, precisely weighing a proper amount (about 40mg corresponding to acetaminophen), placing into a 250ml measuring flask, adding 50ml of 0.4% sodium hydroxide solution and 50ml of water, shaking to dissolve acetaminophen, diluting with water to a scale, shaking uniformly, filtering, precisely weighing 5ml of the subsequent filtrate, placing into a 100ml measuring flask, adding 10ml of 0.4% sodium hydroxide solution, diluting with water to a scale, shaking uniformly, and measuring absorbance at 257nm by ultraviolet-visible spectrophotometry (Chinese pharmacopoeia 2020 edition four general rule 0401);
b) Preparing a reference substance solution: taking acetaminophen reference substance about 40mg, precisely weighing, measuring by the same method, and calculating to obtain the final product.
(2) The chlorpheniramine maleate content determination method refers to high performance liquid chromatography (China pharmacopoeia 2020 edition four general rules 0512) determination, and specifically comprises the following steps:
a) Chromatographic conditions and system suitability test: octadecylsilane chemically bonded silica is used as a filler; phosphate buffer (11.5 g of monoammonium phosphate is taken, a proper amount of water is added to dissolve, 1ml of phosphoric acid is added, the mixture is diluted to 1000ml with water), acetonitrile (75:25) is taken as a mobile phase, and the column temperature is 30 ℃; the detection wavelength was 262nm. The peak-out sequence is maleic acid and chlorpheniramine in turn, the theoretical plate number is not lower than 4000 according to the chlorpheniramine peak, and the separation degree of the chlorpheniramine peak and the adjacent impurity peak is required to meet the requirement.
b) Assay: taking 60g of the product, respectively placing the product into a mortar, adding a proper amount of mobile phase, grinding, quantitatively transferring the mixture into a 25ml measuring flask by using the mobile phase in a fractional manner, shaking to dissolve chlorpheniramine maleate, diluting the mixture to a scale by using the mobile phase, shaking uniformly, filtering, precisely measuring 20 mu l of the continuous filtrate, injecting the filtrate into a liquid chromatograph, and recording a chromatogram;
c) Preparing a reference substance solution: taking a proper amount of chlorpheniramine maleate reference substance, precisely weighing, dissolving with a mobile phase, quantitatively diluting to prepare a solution containing 20 mug of chlorpheniramine maleate in each 1ml, and measuring by the same method. Calculating the content of each tablet/bag according to the peak area by an external standard method, and obtaining the average content of each tablet/bag.
(3) Method for measuring disintegration time
Because the disintegration of the orally disintegrating tablet is very rapid and is difficult to measure according to the pharmacopoeia method, only one tablet is put in a hanging basket at a time, and the orally disintegrating tablet is checked according to the disintegration time limit checking method of the four-part rule 0921 in the year 2020 of Chinese pharmacopoeia until the orally disintegrating tablet completely passes through a screen, the disintegration time limit is marked by a stopwatch, and the average value of each tablet is taken as a measurement result.
a) Determination of the time period for oral disintegration
A single blind experiment involving six volunteers was designed to evaluate the disintegration time of orally disintegrating tablets in the oral cavity of different individuals. After rinsing with clear water, each volunteer took one orally disintegrating tablet separately and placed on the tongue, recorded the time for complete disintegration of the tablet, and calculated the mean and standard deviation.
b) Correlation study of two methods
The same batch of sugar-free pediatric paracetamol and chlorphenamine maleate orally disintegrating tablets are respectively measured by adopting a pharmacopoeia method and an orally disintegrating time limit measuring method, and the correlation of the two methods is determined by drawing.
(4) Dissolution rate measurement method
According to the second method of the dissolution rate measurement of the second appendix of the edition of Chinese pharmacopoeia, the rotating speed is 100rpm, the dissolution medium is 500ml of fresh deaerated distilled water, the temperature is 37+/-0.5 ℃, sampling is carried out at a specified sampling point, the dissolution medium with the same temperature is supplemented, the sampling amount is 5ml, the sample is rapidly filtered through a 0.22 mu m filter membrane after sampling, and the sample is sampled and analyzed according to a content analysis method. The dissolution rate at this sampling time point was calculated. Each time 6 pieces were taken for the experiment, the mean and standard deviation were calculated. The samples were sampled at 0.5min and 1min, respectively, and the cumulative elution amounts were measured.
(4) General Performance inspection
a) Weight difference: taking 10 tablets, precisely weighing the total weight, precisely weighing the average tablet weight, respectively, wherein the weight of each tablet is not more than 5% of the weight difference limit compared with the average tablet weight, and not more than 2 tablets exceeding the weight difference limit and not more than one time of the limit.
b) Hardness: 10 pieces of each sample were taken and their hardness was determined using each hardness indicator.
c) Friability: 10 pieces of the product are taken from each batch, floating dust is blown off, the weight is precisely weighed, and the weight loss is less than 1 percent according to the rule 0923 of the fourth edition of Chinese pharmacopoeia 2020.
d) Determination of Water absorption Properties: the filter paper is fully wetted, the sugar-free pediatric paracetamol orally disintegrating tablet is carefully placed on the filter paper, the filter paper is carefully weighed after being fully wetted, and the water absorption is calculated according to the following formula:
wherein W is water absorption,%; total weight of M pieces after water absorption; m is M 0 The weight of the original tablet is heavy; each experimental protocol was performed three times and the mean and standard deviation were calculated.
(5) Bioavailability detection method
a) Experimental materials
Instrument: ultraviolet spectrophotometer
Reagent: samples prepared from the acetaminophen group, examples 1-9 and comparative examples 1-6.
Color-developing agent: taking 80ml of 0.2mol/L NaOH, adding 10ml of 1% phenolphthalein solution, mixing well, adding 2N Na 2 CO 3 10ml of bromine reagent and mixing uniformly.
b) Experimental method
Experimental animals: healthy rabbits, weighing 1.7-2.2 kg, were fasted 24 hours before the experiment, and fed 4 hours after the administration, 5 animals per group.
Methods and dosages of administration: comparative example 6 granule was dissolved in 50ml of water and then filled into stomach, and orally disintegrating tablet was directly put into mouth of rabbit, and the dosage was 0.2g/kg.
Standard curve: taking 1ml of plasma of non-drug rabbit, adding 6 parts, one part as blank control, and the other 5 parts adding 100, 200, 300, 400 and 600 μg of acetaminophen, shaking uniformly, adding 10% CCl 3 Shaking 1.5ml of COOH, centrifuging for 15min (3000 rpm/min), taking 1ml of supernatant, adding 0.4ml of HCl (3 mol/L) and boiling on a water bath for hydrolysis for 1 hour, cooling to room temperature, adding 7.5ml of color reagent, standing for 1 hour, and measuring the absorbance at 620nm wavelength to obtain a linear equation: y=0.00581+0.00132 x, r= 0.9991.
Recovery rate: in order to consider the influence of other components in the sugar-free pediatric paracetamol orally disintegrating tablet (hereinafter referred to as a sample) on the measurement of the blood concentration of paracetamol, a sample plasma solution is prepared according to the concentrations listed in table 1, the same concentrations of paracetamol are compared, the same concentrations of paracetamol are substituted into a regression equation, the corresponding concentrations are obtained, and recovery rates are calculated respectively, and the results are shown in table 1.
TABLE 1 recovery rate measurement results
Blood concentration measurement: taking 3ml of blank blood from ear vein as control before administration, taking 3ml of blood after administration according to 0.5, 1, 2, 3, 4, 5, 6, 7 hours, anticoagulating with heparin, shaking slightly, centrifuging, and taking 1ml of medicated plasma and blank plasma, and reducing the concentrationPreserving at a temperature for standby. Taking the above blood sample, naturally heating to room temperature, adding 10% CCl 3 COOH 1.5ml, mixing, centrifuging, collecting supernatant 1ml, operating the rest according to standard curve, substituting the measured absorbance into linear equation, and calculating blood concentration.
The index pairs of disintegration time limit, water absorption, hardness, tablet weight difference and friability are shown in table 2; the results of the acetaminophen and chlorpheniramine maleate dissolution experiments are shown in Table 3; the results of the acetaminophen blood concentration and bioavailability (AUC) measurements are shown in table 4.
Table 2 comparative details of disintegration time, water absorption, hardness, tablet weight difference, and friability index
TABLE 3 dissolution test results of paracetamol and chlorpheniramine maleate
TABLE 4 measurement of acetaminophen blood concentration and bioavailability (AUC)
From the test results described in Table 2, it can be seen that the sugar-free small paracetamol orally disintegrating tablets prepared in example 1 are superior to other examples and comparative examples in terms of hardness, water absorption, weight difference, friability, dissolution in 0.5min and 1.0 min. The test results of disintegration time limit and dissolution rate show that the orally disintegrating tablet disintegrates and releases acetaminophen and chlorpheniramine maleate under the condition that saliva in an oral cavity is very little, so that the two medicines can be well covered and attached on an oral mucosa after being released, a high-concentration and high-osmotic-pressure solution film is formed on the surface of the oral mucosa, the medicines can be quickly absorbed into blood through the oral mucosa under the action of high osmotic pressure, the common granules prepared in the comparative example 6 need to be dissolved in enough water to form a solution, and the solution is diluted and then enters the gastrointestinal tract through the esophagus, but the medicine taking mode can lead to partial destruction of the medicines under the action of first pass effect of the liver, only partial absorption of the medicines plays the role of the medicines, and toxicity and adverse reaction caused by liver metabolites can be caused.
In addition, as can be seen from the index detection results (tables 2 to 4) of the orally disintegrating tablets of paracetamol, which were prepared according to examples 1 to 9, the reduction of each auxiliary material significantly affected each test quality index of the samples, particularly, the index of the orally disintegrating tablet of paracetamol, which was more affected for mannitol cross-polymerized maishan co-processed product 500, low-substituted hydroxypropylcellulose L-21 and microcrystalline cellulose, and it can be seen that the above three components have some synergistic effect in improving the quality index of the orally disintegrating tablet of paracetamol, which was prepared according to comparative examples.
In summary, the invention adjusts the prescription of the pediatric paracetamol granule or tablet in the prior art, adds novel auxiliary materials, adopts a novel preparation technology, utilizes the physical and chemical properties of the novel auxiliary materials, and develops a novel preparation orally disintegrating tablet with rapid onset and high bioavailability aiming at the physicochemical properties of main active ingredients of paracetamol, artificial bezoar and chlorpheniramine maleate, thereby not only facilitating the administration of children patients, improving the administration compliance of children patients, but also masking the strong bitter taste of the artificial bezoar to improve the mouthfeel, and separately preparing the oral disintegrating tablet into pellets to release and absorb the oral disintegrating tablet in stomach, thereby avoiding the remarkable reduction of the compliance of children patients due to the generation of strong bitter taste in oral cavity release.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the invention.

Claims (7)

1. The pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet is characterized by comprising the following raw materials in parts by weight:
1250 parts of acetaminophen, 5 parts of chlorpheniramine maleate, 50 parts of artificial bezoar, 500 200 to 2000 parts of mannitol cross-polymerization copolymer Mount common treatment substance, 88 to 880 parts of low-substituted hydroxypropyl cellulose L-21, 100 to 1000 parts of microcrystalline cellulose, 12 to 120 parts of coating material, 17 to 170 parts of flavoring agent, 24 to 240 parts of adhesive, 9 to 90 parts of lubricant, 3 to 30 parts of coating plasticizer, and 2 to 20 parts of pH regulator and effervescent agent;
the pH regulator and the effervescent agent are one or more of sodium bicarbonate, sodium carbonate, magnesium carbonate and basic magnesium carbonate;
the adhesive is povidone;
the coating material is one or more of Uttky E12.5, ethylcellulose, uttky E30, polyacrylic resin II, polyacrylic resin III, methyl vinyl ether/maleic anhydride copolymer and hydroxypropyl methylcellulose phthalate.
2. The pediatric paracetamol, the chlorphenamine maleate and the orally disintegrating tablet according to claim 1, wherein the lubricant is one or more of sodium stearyl fumarate, sodium stearate, stearic acid, glyceryl palmitostearate and zinc stearate.
3. The pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet of claim 1, wherein the coating plasticizer is one or more of dibutyl sebacate, dibutyl phthalate, diethyl phthalate, triethyl citrate, dimethyl phthalate.
4. The pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet of claim 1, wherein the flavoring agent is one or more of citric acid, sucralose, aspartame, acesulfame potassium, citric acid, and alitame.
5. The method for preparing pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet according to any of claims 1-4, wherein the method comprises the steps of:
s1: uniformly mixing an adhesive, a flavoring agent and chlorpheniramine maleate in an ethanol solution to prepare an adhesive solution for later use;
s2: adding a coating plasticizer into the coating material and uniformly mixing to obtain a coating liquid;
s3: mixing artificial bezoar, 5-15% low substituted hydroxypropyl cellulose L-21 and 5-15% mannitol cross-polymerization copolymer Maishan co-processed product 500 uniformly, adding 1-10% binder solution in S1 to prepare soft material, granulating with screen, drying, and finishing with screen;
S4: placing the material subjected to the finishing of the step S3 into a coating machine, spraying coating liquid in the step S2, and fully drying layer by layer to obtain pellets;
s5: adding 50-60% of low-substituted hydroxypropyl cellulose L-21 and 85-95% of mannitol cross-polymerization copolymerization Maishan co-processed substance 500 and microcrystalline cellulose into acetaminophen, uniformly mixing, adding the rest adhesive solution in S1, uniformly mixing, preparing into soft material, granulating, drying and granulating to obtain pediatric paracetamol orally disintegrating tablet particles;
s6: and (3) adding the pellets prepared in the step (S4), a lubricant, a pH regulator and the balance of low-substituted hydroxypropyl cellulose L-21 into the pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet granules in the step (S5), uniformly mixing, and tabletting to prepare the pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet.
6. The method for preparing pediatric paracetamol, the orally disintegrating tablet according to claim 5, wherein the working parameters of the coating machine in S4 are as follows: the rotating speed of the coating machine is controlled to be 2-3r/min, the air inlet temperature is 60-70 ℃ and is preheated to the air outlet temperature of 40-45 ℃, and then the rotating speed of the coating machine is adjusted to be 7-9r/min and the air inlet temperature is 60-70 ℃.
7. The method for preparing pediatric paracetamol, the orally disintegrating tablet according to claim 5, wherein the drying conditions in S3 and S5 are: boiling and drying at 70-80deg.C until the water content of the material is 2.5-3.2%.
CN202210942080.7A 2022-08-08 2022-08-08 Pediatric paracetamol, chlorphenamine maleate orally disintegrating tablet and preparation method thereof Active CN115300468B (en)

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CN1872039A (en) * 2006-04-17 2006-12-06 毛晓敏 Rotula of acetaminopher suitable for children to take, and prepartion method
CN101744836A (en) * 2008-12-18 2010-06-23 海南中化联合制药工业有限公司 Pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate orally disintegrating tablet preparation and preparing method thereof
CN104023712A (en) * 2011-12-28 2014-09-03 株式会社三养生物制药 Highly robust fast-disintegrating tablet and process for manufacturing the same
CN107252419A (en) * 2010-12-22 2017-10-17 巴斯夫欧洲公司 Quickly disintegrated solid coated dosage form

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US20080286343A1 (en) * 2007-05-16 2008-11-20 Dzenana Cengic Solid form

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1823843A (en) * 2005-12-23 2006-08-30 刘春� Child ammonia phenol alkyl amine affervescent tablet and its preparation method
CN1872039A (en) * 2006-04-17 2006-12-06 毛晓敏 Rotula of acetaminopher suitable for children to take, and prepartion method
CN101744836A (en) * 2008-12-18 2010-06-23 海南中化联合制药工业有限公司 Pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate orally disintegrating tablet preparation and preparing method thereof
CN107252419A (en) * 2010-12-22 2017-10-17 巴斯夫欧洲公司 Quickly disintegrated solid coated dosage form
CN104023712A (en) * 2011-12-28 2014-09-03 株式会社三养生物制药 Highly robust fast-disintegrating tablet and process for manufacturing the same

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