CN114681420A - Phloroglucinol controlled-release tablet and preparation method thereof - Google Patents
Phloroglucinol controlled-release tablet and preparation method thereof Download PDFInfo
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- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
Abstract
The invention discloses a phloroglucinol controlled release tablet and a preparation method thereof. A controlled release tablet containing phloroglucinol comprises a sustained release part and a quick release part; the immediate release portion contains phloroglucinol in a prescribed amount of 2-50%; the sustained-release part comprises citric acid and caprylic capric glyceride. The phloroglucinol controlled-release tablet provided by the invention contains a slow-release part and a quick-release part, and can not only take effect quickly, but also release slowly after being taken by a patient, thereby effectively reducing the medication burden of the patient. The phloroglucinol controlled release tablet provided by the invention contains citric acid and caprylic capric glyceride, the combination of the citric acid and the caprylic capric glyceride plays a good role in stabilizing phloroglucinol, and the antioxidant effect is better than that of the single application of the citric acid or the caprylic capric glyceride.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and relates to a phloroglucinol controlled-release tablet and a preparation method thereof.
Background
Phloroglucinol as a spasmolytic drug is usually prepared into injection or freeze-dried powder for use, and is administered by the following method: 1. intramuscular or intravenous injection. 2. Intravenous drip: instilling in 5% or 10% glucose injection. It is used for treating acute spastic pain caused by digestive system and biliary tract dysfunction. 2. Acute spasmodic urinary tract, bladder, renal colic. 3. And (4) gynecological spasmodic pain.
After intravenous injection, the half-life period of the blood concentration of the phloroglucinol injection is about 15 minutes, the blood concentration is quickly reduced within 4 hours after administration, the half-life period is short, so that multiple administrations are often needed, and the dosage is higher, thereby increasing the medication burden of patients.
Compared with injection, the phloroglucinol oral chewable tablet and the phloroglucinol oral freeze-dried tablet are developed by domestic and foreign medicine enterprises, have the characteristics of convenient administration, quick disintegration and quick response.
However, the phloroglucinol oral chewable tablets and the oral freeze-dried tablets still cannot solve the defect that the plasma concentration of the phloroglucinol cannot be maintained, and patients still need to take the phloroglucinol for multiple times, and the daily administration frequency reaches 3 times.
In addition, during the development of phloroglucinol formulations, oxidative impurities are often increased during preparation and storage due to the susceptibility of the phenolic hydroxyl group of phloroglucinol to oxidation. Patent CN201310660189.2 avoids oxidation of phloroglucinol in wet granulation by adding sodium bisulfite to the formulation, but sodium bisulfite is irritating and gives off sulfur dioxide with long-term mixing with phloroglucinol, with obvious drawbacks.
Disclosure of Invention
An object of the present invention is to provide a formulation composition of a phloroglucinol controlled-release tablet which can provide a bioactive substance to maintain a therapeutic concentration for a long time by means of a controlled release rate of a drug, and the formulation of the phloroglucinol controlled-release tablet provided by the present invention can effectively prevent oxidation of phloroglucinol during preparation and storage.
The invention also aims to provide a preparation method of the phloroglucinol-containing controlled release tablet.
The purpose of the invention can be realized by the following technical scheme:
a phloroglucinol controlled release tablet comprises a sustained release part and a quick release part; the immediate release portion contains phloroglucinol in a prescribed amount of 2-50%; the auxiliary materials of the slow release part comprise one or more of skeleton materials, controlled release membrane materials, pore-forming agents, permeation-promoting agents, adhesives, wetting agents and plasticizers; the slow release part comprises citric acid and caprylic-capric glyceride.
As a preferable preference of the invention, the dosage of the citric acid of the slow release part is 2 to 5 percent of the dosage of the phloroglucinol of the slow release part; the dosage of the sustained-release part of the caprylic capric glyceride is 2 to 5 percent of the dosage of the sustained-release part of the phloroglucinol.
As a further preferred of the invention, the framework material comprises one or more of sodium carboxymethyl starch, croscarmellose sodium, crospovidone and low-substituted hydroxypropyl cellulose; the controlled release membrane material comprises celluloses and resin auxiliary materials, wherein the celluloses comprise one or more of cellulose acetate, ethyl cellulose and hydroxypropyl methyl cellulose titanate, and the resins comprise one or more of acrylic resin and ethylene acrylic acid copolymer; the pore-forming agent comprises one or more of mannitol, polyethylene glycols, glycerol, urea, water-soluble inorganic salt and micromolecular saccharides; the penetration enhancer comprises one or more of sodium chloride, lactose, sucrose, glucose, potassium chloride, mannitol and fructose; the adhesive comprises one or more of polyvinylpyrrolidone and hydroxypropyl methylcellulose; the wetting agent comprises one or more of water, ethanol and ethanol-water solutions with various concentrations; the plasticizer comprises one or more of triethyl citrate, methyl phthalate, ethyl phthalate and polyethylene glycol.
As a further optimization of the invention, the controlled release tablet also comprises a lubricant and a solvent, wherein the lubricant comprises one or more of talcum powder, superfine silica gel powder, magnesium stearate, starch, stearic acid and paraffin.
As a preferred of the invention, the quick-release part comprises citric acid and caprylic capric glyceride; the dosage of the sustained-release part of the citric acid is 2 to 5 percent of that of the sustained-release part of the phloroglucinol; the dosage of the sustained-release part of the caprylic capric glyceride is 2 to 5 percent of the dosage of the sustained-release part of the phloroglucinol.
The invention also provides a method for preparing the phloroglucinol-containing controlled release tablet, which comprises the following steps:
a. uniformly mixing phloroglucinol, citric acid, caprylic capric glyceride and a framework material for the slow release layer;
b. mixing and dissolving the adhesive and the wetting agent, and adding the mixture into the mixture prepared in the step a to prepare a soft material;
c. and c, preparing the soft material obtained in the step b into wet granules, drying the wet granules, finishing the granules, adding a lubricant, and uniformly mixing to obtain the sustained-release layer granules.
d. The phloroglucinol used for the quick release layer is mixed with other components of the quick release layer, and then is prepared into quick release granules by dry granulation or wet granulation.
e. And c, tabletting the sustained-release granules obtained in the step c, adding the quick-release layer granules, and pressing and molding to obtain the double-layer tablet.
As an improvement measure of the preparation method, after the sustained-release granules are tableted in the step e, an inner coating solution prepared from a controlled-release membrane material and a pore-forming agent is coated, and then the quick-release layer granules are added for pressure forming to obtain the double-layer tablet.
As another improvement measure of the preparation method, after the sustained-release granules are tableted, the controlled-release membrane material is prepared into a prepared inner coating liquid to coat, then laser drilling is carried out, and then the quick-release layer granules are added to carry out pressure molding, thus obtaining the phloroglucinol controlled-release tablet.
As a further improvement measure for preparing the phloroglucinol controlled release tablet, the auxiliary seepage liquid can be added in the step e, and the plasticizer can be added in the step a.
As another method for preparing the phloroglucinol-containing controlled-release tablet, the following steps are carried out:
a. uniformly mixing phloroglucinol for the slow release layer, a framework material, citric acid and caprylic capric glyceride;
b. mixing and dissolving the adhesive and the wetting agent, and adding the mixture into the mixture prepared in the step a to prepare a soft material;
c. c, preparing the soft material obtained in the step b into wet granules, drying the wet granules, finishing granules, adding a lubricant, and uniformly mixing to obtain sustained-release layer granules;
d. mixing phloroglucinol used for the quick release layer with other components of the quick release layer to prepare liquid coating liquid;
e. and c, tabletting the sustained-release granules obtained in the step c, and coating the sustained-release tablet core by using the liquid prepared in the step d to obtain the phloroglucinol controlled-release tablet.
As another design of the prescription, the phloroglucinol controlled release tablet also contains trimethoxybenzene.
The preparation method comprises the following steps:
uniformly mixing phloroglucinol for the slow release part, a framework material, citric acid and caprylic/capric glyceride, and adding a certain amount of plasticizer before mixing; mixing and dissolving the adhesive and the wetting agent, and adding the mixture into the mixture prepared in the step a to prepare a soft material; c, preparing the soft material obtained in the step b into wet granules, drying the wet granules, finishing granules, adding a lubricant, and uniformly mixing to obtain slow-release part granules;
mixing phloroglucinol used for the quick-release part with auxiliary materials of the quick-release layer, and preparing the mixture into quick-release granules by dry granulation or wet granulation;
as a controlled release technology, the controlled release membrane can also play a controlled release role, the controlled release membrane material and a pore-forming agent are mixed and dissolved by a wetting agent to prepare an inner coating solution, and a certain amount of permeation-assisting liquid can also be added into the coating solution.
If no pore-forming agent is added into the controlled release film, the hole can also be formed by a laser punching method after coating.
Tabletting the delayed release granule, coating with inner coating solution, adding the quick release layer granule, and pressure molding to obtain double-layer tablet.
The bi-layer tablets may be coated with a fast-dissolving coating material.
As another technical means, the immediate release layer can also be obtained by preparing phloroglucinol into a solution and coating the solution outside the controlled release layer by a coating method.
Has the advantages that:
1. the phloroglucinol controlled-release tablet provided by the invention contains a slow-release part and a quick-release part, and can not only take effect quickly, but also release slowly after being taken by a patient, thereby effectively reducing the medication burden of the patient.
2. The phloroglucinol controlled release tablet provided by the invention contains citric acid and caprylic capric glyceride, the combination of the citric acid and the caprylic capric glyceride plays a good role in stabilizing phloroglucinol, and the antioxidant effect is better than that of the single application of the citric acid or the caprylic capric glyceride.
Detailed Description
Example 1
Prescription design:
sieving and mixing 700g of phloroglucinol for the sustained-release part and 3000g of crosslinked polyvinylpyrrolidone, adding 400g of purified water, 14g of sustained-release part caprylic-capric glyceride and 14g of sustained-release part citric acid, mixing and sieving to prepare a soft material; drying the wet granules, finishing, adding a lubricant, and uniformly mixing to obtain sustained-release layer granules;
mixing 700g of phloroglucinol for a quick-release part, 1500g of corn starch, 2000g of mannitol, 15g of quick-release part caprylic/capric glyceride and 200g of povidone K30, adding 400g of purified water and 15g of citric acid, and performing wet granulation to prepare quick-release granules;
tabletting the sustained-release granules, coating with an inner coating solution, adding the quick-release layer granules, and performing pressure molding, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablet.
Example 2
Prescription design:
sieving and mixing 800g of phloroglucinol for the sustained-release part, 3000g of ethyl cellulose, 150g of hydroxypropyl methyl cellulose, 16g of caprylic capric glyceride for the sustained-release part and 24g of citric acid for the sustained-release part, adding 700g of purified water, mixing and sieving to prepare a soft material; drying the wet granules, finishing the granules, adding 10g of talcum powder, and uniformly mixing to obtain slow-release partial granules;
mixing 600g of phloroglucinol for the quick-release part, povidone K30200g and 1700g of mannitol, performing dry granulation, and adding 12g of magnesium stearate to prepare quick-release granules;
and tabletting the sustained-release granules, coating the sustained-release granules with an inner coating solution, adding the quick-release part of granules, and performing pressure forming, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablets.
Example 3
Prescription design:
sieving and mixing 800g of phloroglucinol for the sustained-release part, 80g of trimethyl phloroglucinol, 3700g of croscarmellose sodium and 40g of sustained-release part caprylic/capric glyceride, adding 900g of purified water and 40g of sustained-release part citric acid, mixing and sieving to prepare a soft material; drying the wet granules, finishing the granules, adding 10g of aerosil, and uniformly mixing to obtain slow-release partial granules;
mixing and dissolving 24g of acrylic resin, 5g of mannitol and 240g of ethanol to prepare inner coating liquid;
mixing 500g of phloroglucinol for the quick-release part, 50g of trimethyl phloroglucinol, 1100g of corn starch, 1600g of mannitol and 200g of povidone K30, adding 400g of purified water, 18g of caprylic/capric glyceride and 10g of citric acid, performing wet granulation, drying, adding 12g of magnesium stearate, and preparing into quick-release granules;
tabletting the sustained-release granules, coating with an inner coating solution, adding the quick-release part of granules, and carrying out pressure molding, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablets.
Example 4
Prescription design:
sieving 900g of phloroglucinol for the slow release part, 3500g of hydroxypropyl cellulose and 18g of slow release part caprylic/capric glyceride, mixing, adding 1000g of ethanol, 5g of carbomer, 45g of caprylic/capric glyceride and 18g of citric acid, mixing, and sieving to obtain a soft material; drying the wet granules, finishing the granules, adding 10g of talcum powder, and uniformly mixing to obtain slow-release partial granules;
mixing 8g of cellulose acetate, 16g of methyl phthalate and 240g of ethanol, and dissolving to obtain an inner coating solution;
mixing 500g of phloroglucinol for the quick-release part, 1200g of corn starch, 1300g of mannitol and 60g of povidone K90, adding 400g of purified water, 16g of caprylic-capric glyceride and 10g of citric acid, performing wet granulation, drying, adding 8g of magnesium stearate and 4g of talcum powder, and preparing the quick-release granules;
tabletting the sustained-release granules, coating with an inner coating solution, performing laser drilling on the coating, adding the quick-release part of granules, and performing pressure molding, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablet.
Example 5
Prescription design:
sieving and mixing 1470g of phloroglucinol for slow release part, 500g of hydroxypropyl cellulose and 3200g of croscarmellose sodium, adding 3000g of purified water, 29 g of slow release part caprylic/capric glyceride and 32 g of slow release part citric acid, mixing and sieving to obtain a soft material; drying the wet granules, finishing the granules, adding 11g of talcum powder, and uniformly mixing to obtain slow-release partial granules;
mixing 30g of phloroglucinol for the quick-release part, 100g of mannitol and 6g of povidone K90, adding 110g of purified water, 0.6g of caprylic-capric glyceride and 0.6g of citric acid, and dissolving;
tabletting the sustained-release granules, then adding a quick-release part of liquid for spray coating, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablet.
Example 6 (sustained Release formulation)
Prescription design:
| components | Weight (g) |
| Phloroglucinol | 1300 |
| Croscarmellose sodium | 3100 |
| The sustained release part is purified water | 900 |
| Silica gel micropowder | 10 |
| Acrylic resin | 24 |
| Mannitol | 5 |
| Ethanol | 240 |
1300g of phloroglucinol and 3100g of croscarmellose sodium for slow release part are sieved and mixed, 900g of purified water is added, and sieving is carried out to prepare soft materials; drying the wet granules, finishing the granules, adding 10g of aerosil, and uniformly mixing to obtain slow-release granules;
mixing 24g of acrylic resin, 5g of mannitol and 240g of ethanol, and dissolving to obtain a coating solution;
tabletting the sustained-release granules, and coating with an inner coating liquid to obtain the phloroglucinol controlled-release tablet.
Example 7 (comparative example 1)
Prescription design:
sieving and mixing 700g of phloroglucinol and 3000g of crosslinked polyvinylpyrrolidone for sustained release, adding 400g of purified water and 80g of caprylic/capric glyceride for sustained release, mixing and sieving to obtain a soft material; drying the wet granules, finishing, adding a lubricant, and uniformly mixing to obtain sustained-release layer granules;
mixing 700g of phloroglucinol for a quick-release part, 1500g of corn starch, 2000g of mannitol, 90g of quick-release part caprylic/capric glyceride and 200g of povidone K30, adding 400g of purified water, and performing wet granulation to prepare quick-release granules;
tabletting the sustained-release granules, coating with an inner coating solution, adding the quick-release layer granules, and performing pressure molding, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablet.
Example 8: comparative example 2
Prescription design:
sieving and mixing 700g of phloroglucinol for the sustained-release part and 3000g of crosslinked polyvinylpyrrolidone, adding 400g of purified water and 90g of citric acid for the sustained-release part, mixing and sieving to prepare a soft material; drying the wet granules, finishing, adding a lubricant, and uniformly mixing to obtain sustained-release layer granules;
mixing 700g of phloroglucinol used for a quick-release part, 1500g of corn starch, 2000g of mannitol and 200g of povidone K30, adding 400g of purified water and 100g of citric acid, and performing wet granulation to prepare quick-release granules;
and tabletting the sustained-release granules, coating the sustained-release granules with an inner coating solution, then adding the quick-release layer granules, and performing pressure molding, and coating the obtained plain tablets with an Opadry II coating material to obtain the phloroglucinol controlled-release double-layer tablet.
The results of the animal pharmacokinetic experiments were as follows:
in this study, male beagle dogs were randomly divided into 6 groups, and the phloroglucinol controlled-release tablets, sustained-release tablets (example 6) prepared in examples 1 to 5 and commercially available triphenolic orally disintegrating tablets were administered, and blood was collected 0 to 24 hours after administration. The concentration of phloroglucinol in the plasma of dogs was determined according to the established and validated LC-MS/MS method.
| Prescription | tmax | t1/2 | Cmax | AUC |
| Example 1 | (0.4±0.07)h | (15.3±0.9)h | (8923±923.6)ng.L-1 | 20126±3202ng/ml.h |
| Example 2 | (0.4±0.06)h | (16.3±1.1)h | (8972±891.3)ng.L-1 | 23145±2203ng/ml.h |
| Example 3 | (0.3±0.09)h | (17.9±0.8)h | (9585±962.7)ng.L-1 | 22036±2306ng/ml.h |
| Example 4 | (0.4±0.06)h | (18.3±1.2)h | (9326±723.9)ng.L-1 | 20156±1986ng/ml.h |
| Example 5 | (0.7±0.08)h | (17.5±1.3)h | (7832±751.6)ng.L-1 | 21456±3102ng/ml.h |
| Example 6 | (1.3±0.09)h | (18.5±1.4)h | (7931±839.7)ng.L-1 | 22362±3188ng/ml.h |
| Spafen | (0.3±0.07)h | (4.3±0.8)h | (9130±926.6)ng.L-1 | 12853±1320ng/ml.h |
As can be seen from the above data, the phloroglucinol controlled-release tablets provided in examples 1 to 5 of the present invention have rapid onset of action and significantly prolonged duration of action.
Oxide detection study:
the phloroglucinol controlled-release tablets prepared in examples 1 to 5 were tested for degradation impurities together with the general sustained-release tablet (control) prepared in example 6.
| Examples | Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Example 6 |
| Whether or not there is oxide generation | Whether or not | Whether or not | Whether or not | Whether or not | Whether or not | Is that |
| Oxide content (%) | / | / | / | / | / | 0.05 |
Stability study:
the phloroglucinol controlled-release tablets prepared in examples 1 to 5 were subjected to stability tests together with the general sustained-release tablet (control group) prepared in example 6, example 7 (comparative example 1) and example 8 (comparative example 2) under the examination conditions: storing at 25 + -2 deg.C for 36 months, and detecting whether there is oxide.
The phloroglucinol controlled-release tablet provided by the invention is added with the citric acid and the caprylic capric glyceride, wherein the citric acid plays a role in stabilizing hydrogen bonds of phloroglucinol hydroxyl, the caprylic capric glyceride plays a role in synergism, the effect which cannot be achieved by the combination of the citric acid and the caprylic capric glyceride is higher in antioxidation effect than that of the citric acid or the caprylic capric glyceride which is used alone, the dosage of an antioxidant is unexpectedly reduced, and the oxidation problem of the phloroglucinol controlled-release tablet in the preparation and storage processes can be effectively avoided by the combination of the citric acid and the caprylic capric glyceride.
In conclusion, the phloroglucinol controlled-release tablet provided by the embodiment of the invention has the functions of quick release and slow release, and can achieve the functions of quick response and slow release after being taken by patients.
The phloroglucinol controlled release tablet provided by the invention is added with citric acid and caprylic capric glyceride, and the combination of the citric acid and the caprylic capric glyceride unexpectedly finds that the phloroglucinol controlled release tablet has an antioxidant effect in the preparation and storage processes.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A phloroglucinol controlled-release tablet, which is characterized in that the controlled-release tablet comprises a sustained-release part and an immediate-release part;
the immediate release portion contains phloroglucinol in a prescribed amount of 2-50%; the auxiliary materials of the slow release part comprise one or more of a framework material, a controlled release membrane material, a pore-forming agent, a penetration-assisting agent, an adhesive, a wetting agent and a plasticizer; the sustained-release part comprises citric acid and caprylic capric glyceride.
2. The phloroglucinol controlled-release tablet according to claim 2, wherein: the dosage of the sustained-release part of the citric acid is 2 to 5 percent of that of the sustained-release part of the phloroglucinol; the dosage of the sustained-release part of the caprylic capric glyceride is 2 to 5 percent of the dosage of the sustained-release part of the phloroglucinol.
3. The phloroglucinol controlled-release tablet according to claim 2, wherein:
the framework material is selected from one or more of sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose;
the controlled release membrane material is selected from cellulose and resin auxiliary materials, the cellulose auxiliary materials are selected from one or more of cellulose acetate, ethyl cellulose and hydroxypropyl methyl cellulose titanate, and the resin auxiliary materials are selected from one or more of acrylic resin and ethylene acrylic acid copolymer;
the pore-forming agent is selected from one or more of mannitol, polyethylene glycols, glycerol, urea, water-soluble inorganic salt and micromolecular saccharides;
the penetration enhancer is selected from one or more of sodium chloride, lactose, sucrose, glucose, potassium chloride, mannitol and fructose;
the adhesive is selected from one or more of polyvinylpyrrolidone and hydroxypropyl methyl cellulose;
the wetting agent is selected from one or more of water, ethanol and ethanol-water solution with various concentrations;
the plasticizer is selected from one or more of triethyl citrate, methyl phthalate, ethyl phthalate and polyethylene glycol.
4. The phloroglucinol controlled-release tablet according to claim 3, wherein: the controlled release tablet also comprises a lubricant and a solvent, wherein the lubricant is selected from one or more of talcum powder, superfine silica gel powder, magnesium stearate, starch, stearic acid and paraffin.
5. The phloroglucinol controlled-release tablet according to any one of claims 1 to 4, wherein: the quick-release part comprises citric acid and caprylic capric glyceride; the dosage of the slow-release part of citric acid is 2 to 5 percent of that of the slow-release part of phloroglucinol; the dosage of the sustained-release part of the caprylic capric glyceride is 2 to 5 percent of the dosage of the sustained-release part of the phloroglucinol.
6. A method for preparing the phloroglucinol controlled-release tablet according to any one of claims 1 to 4, comprising the steps of:
a. uniformly mixing phloroglucinol, citric acid, caprylic capric glyceride and a framework material for the slow release layer;
b. mixing and dissolving the adhesive and the wetting agent, and adding the mixture into the mixture prepared in the step a to prepare a soft material;
c. c, preparing the soft material obtained in the step b into wet granules, drying the wet granules, finishing granules, adding a lubricant, and uniformly mixing to obtain sustained-release layer granules;
d. mixing phloroglucinol used for the quick release layer with other components of the quick release layer, and then preparing the quick release granules by dry granulation or wet granulation;
e. and c, tabletting the sustained-release granules obtained in the step c, adding the quick-release layer granules, and pressing and molding to obtain the phloroglucinol controlled-release tablet.
7. The method for preparing phloroglucinol controlled-release tablets according to claim 5, wherein after the sustained-release granules are tableted in the step e, an inner coating solution prepared from a controlled-release membrane material and a pore-forming agent is coated, and then the quick-release layer granules are added for pressure forming to obtain a double-layer tablet;
or, after the sustained-release particles are tabletted, coating the inner coating liquid prepared by preparing the controlled-release film material, then performing laser drilling, adding the quick-release layer particles, and performing pressure molding to obtain the double-layer tablet.
8. The method for preparing a phloroglucinol controlled-release tablet according to claims 6-7, wherein a permeation assisting solution may be further added in step e, and a plasticizer may be further added in step a.
9. A method for preparing phloroglucinol controlled release tablets is characterized by comprising the following steps:
a. uniformly mixing phloroglucinol, citric acid, caprylic/capric glyceride and a framework material for the slow-release layer;
b. mixing and dissolving the adhesive and the wetting agent, and adding the mixture into the mixture prepared in the step a to prepare a soft material;
c. c, preparing the soft material obtained in the step b into wet granules, drying the wet granules, finishing granules, adding a lubricant, and uniformly mixing to obtain slow-release layer granules;
d. mixing phloroglucinol used for the quick release layer with other components of the quick release layer to prepare liquid coating liquid;
e. and c, tabletting the sustained-release granules obtained in the step c, and coating the sustained-release granules with the liquid obtained in the step d to obtain the phloroglucinol controlled-release tablet.
10. The controlled-release phloroglucinol tablet of claim 1, further comprising trimethoxybenzene.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202011566287.6A CN114681420A (en) | 2020-12-25 | 2020-12-25 | Phloroglucinol controlled-release tablet and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116440204A (en) * | 2023-04-26 | 2023-07-18 | 江西维莱营健高科有限公司 | Capsule with immunity enhancing function and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116440204A (en) * | 2023-04-26 | 2023-07-18 | 江西维莱营健高科有限公司 | Capsule with immunity enhancing function and preparation method thereof |
| CN116440204B (en) * | 2023-04-26 | 2024-01-30 | 江西维莱营健高科有限公司 | Capsule with immunity enhancing function and preparation method thereof |
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