CN118252803A - Tandospirone citrate pulse preparation and preparation method and application thereof - Google Patents
Tandospirone citrate pulse preparation and preparation method and application thereof Download PDFInfo
- Publication number
- CN118252803A CN118252803A CN202410394239.5A CN202410394239A CN118252803A CN 118252803 A CN118252803 A CN 118252803A CN 202410394239 A CN202410394239 A CN 202410394239A CN 118252803 A CN118252803 A CN 118252803A
- Authority
- CN
- China
- Prior art keywords
- pulse
- preparation
- citrate
- tandospirone citrate
- release preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 106
- 229950000505 tandospirone Drugs 0.000 title claims abstract description 84
- CEIJFEGBUDEYSX-FZDBZEDMSA-N tandospirone Chemical compound O=C([C@@H]1[C@H]2CC[C@H](C2)[C@@H]1C1=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 CEIJFEGBUDEYSX-FZDBZEDMSA-N 0.000 title claims abstract 34
- 239000003814 drug Substances 0.000 claims abstract description 29
- 229940079593 drug Drugs 0.000 claims abstract description 22
- 238000000576 coating method Methods 0.000 claims abstract description 20
- 239000011248 coating agent Substances 0.000 claims abstract description 12
- 239000000463 material Substances 0.000 claims abstract description 12
- 239000002346 layers by function Substances 0.000 claims abstract description 7
- 238000012377 drug delivery Methods 0.000 claims abstract description 5
- 239000008188 pellet Substances 0.000 claims description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 24
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 23
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 22
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 22
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 22
- 238000005507 spraying Methods 0.000 claims description 22
- 239000001069 triethyl citrate Substances 0.000 claims description 22
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 22
- 235000013769 triethyl citrate Nutrition 0.000 claims description 22
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 238000005303 weighing Methods 0.000 claims description 13
- 229920003139 Eudragit® L 100 Polymers 0.000 claims description 12
- 229960003943 hypromellose Drugs 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 12
- 229920003141 Eudragit® S 100 Polymers 0.000 claims description 11
- 238000009472 formulation Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 9
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 9
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 9
- 239000000853 adhesive Substances 0.000 claims description 6
- 230000001070 adhesive effect Effects 0.000 claims description 6
- 229960001375 lactose Drugs 0.000 claims description 6
- 239000010410 layer Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000007779 soft material Substances 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920003138 Eudragit® L 30 D-55 Polymers 0.000 claims description 2
- 229920002301 cellulose acetate Polymers 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 2
- 238000001125 extrusion Methods 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 2
- 238000005563 spheronization Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 17
- 239000008280 blood Substances 0.000 abstract description 11
- 210000004369 blood Anatomy 0.000 abstract description 11
- 239000003405 delayed action preparation Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- 208000020016 psychiatric disease Diseases 0.000 abstract description 4
- 210000002249 digestive system Anatomy 0.000 abstract description 3
- 238000001727 in vivo Methods 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000002459 sustained effect Effects 0.000 abstract 1
- DMLGUJHNIWGCKM-DPFKZJTMSA-N tandospirone citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.O=C([C@@H]1[C@H]2CC[C@H](C2)[C@@H]1C1=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 DMLGUJHNIWGCKM-DPFKZJTMSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000006187 pill Substances 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012738 dissolution medium Substances 0.000 description 3
- 238000011978 dissolution method Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000007667 floating Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000000541 pulsatile effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tandospirone citrate pulse preparation, a preparation method and application thereof, and belongs to the technical field of sustained and controlled release preparations, wherein the tandospirone citrate pulse preparation is a tandospirone citrate 3-time pulse release preparation based on a multiparticulate drug delivery system. The tandospirone citrate pulse preparation provided by the invention is a 3-time pulse release preparation, and different functional layer coating materials are selected to be composed according to the detention time of the preparation in different parts/physiological environments in a digestive system so as to ensure the release speed and total dosage of active ingredients; the coating materials with different pulses have stable effects in the in-vivo environment, do not have the phenomenon of early/late dissolution, can effectively ensure the stable blood concentration in the body of a patient, reduce the medication psychological pressure of the patient, and improve the medication compliance of the patient with mental diseases; the prepared sustained release preparation has proper size and is easy to swallow.
Description
Technical Field
The invention relates to the technical field of sustained release preparations, in particular to a tandospirone citrate pulse preparation and a preparation method and application thereof.
Background
Tandospirone citrate (Tandospirone citrate, API) is an anxiolytic which selectively acts on the 5-HT 1A receptor in the brain and is developed by the japanese summonic pharmaceutical co-ltd and marketed in japan in 1996 as a tablet under the trade name sediel in the specifications 5mg, 10mg and 20mg. Wherein, the 10mg specification is imported and imported domestically, and the commodity name is Hilde.
The tandospirone citrate is clinically used for treating anxiety states (such as generalized anxiety disorder) caused by various neurosis and anxiety states accompanied by somatic diseases such as primary hypertension, peptic ulcer and the like. The medicine taking method and the dosage are as follows: the dosage of the medicine for adults is 10 mg/time, 3 times a day, and the dosage can be appropriately increased or decreased according to the age, symptoms and the like of patients, but the daily dosage is not more than 60mg or is in compliance with the doctor's advice.
The original ground product is a film coated tablet, belongs to a quick-release tablet, and can be dissolved out rapidly in vitro and completely in 10min in different media. When a healthy adult orally takes 20mg once, the original ground product can be absorbed rapidly, the highest blood concentration can be achieved after 0.8-1.4 h, and the blood concentration is eliminated rapidly, the half-life period (t 1/2) in blood is about 1.2-1.4 h, and the blood concentration is basically not influenced by fasted food. The blood concentration of the healthy adult is the same as that of the adult taken once after the healthy adult takes 10mg every time, 3 times a day and 5 days continuously, which indicates that the healthy adult has no accumulation in the body.
At present, the commercial preparation is a quick release preparation, and needs to be frequently administered every day, and has the defects of large fluctuation of blood concentration, poor patient compliance and the like, and particularly has prominent compliance problem for patients with dysphagia. In addition, a three-day dosing regimen can increase the psychological burden of administering medication to patients with mental disorders, creating a "pubic feeling".
Patent CN1899287a discloses a preparation method of a tandospirone citrate sustained-release tablet. The technical patent slows down the release speed of tandospirone citrate by means of the action of a slow-release framework material (such as hypromellose K4M) to generate more gentle and durable blood concentration, and can reduce the administration frequency from 1 day 3 to 1 day 2. However, the administration mode of 2 times a day is still not effective in reducing the psychological burden of patient medication.
Patent CN113018271a discloses a preparation method of a 1-day 1-time tandospirone citrate sustained-release preparation, in particular to a floating gastric retention tablet. The prescription composition of the sustained-release preparation mainly comprises tandospirone citrate, a sustained-release framework material (polyethylene oxide), a bleaching aid (sodium carbonate, sodium bicarbonate, potassium bicarbonate, calcium carbonate or magnesium carbonate) and the like, and can prolong the residence time of the medicine in the stomach, so that the medicine can be fully released and absorbed, and the bioavailability of the medicine is improved. However, the preparation disclosed by the invention has a large volume (16.4 mm multiplied by 7.9 mm), is not easy to swallow by patients, and is not beneficial to improving the medication compliance of the patients. In addition, the gastric-floating preparation is administered in a single dose, and may cause burst release or poor floating performance of individual preparations, and is rapidly emptied by the stomach, thereby failing to achieve the intended sustained-release effect.
Disclosure of Invention
The invention aims to provide a tandospirone citrate pulse preparation, a preparation method and application thereof, and aims to solve the problems that the commercially available tandospirone citrate preparation is a quick-release preparation, is frequently administered every day, is arduous and laborious, can increase the medication psychological burden of a patient, generates a 'pubic feeling', causes the fluctuation of the blood concentration of the patient, has poor patient compliance and the like.
In order to achieve the aim, the invention provides a tandospirone citrate pulse preparation, a preparation method and application thereof. A tandospirone citrate pulsatile formulation which is a tandospirone citrate 3 pulsatile release formulation based on a multiparticulate drug delivery system; the multiparticulate drug delivery system is a granule or pellet preparation, each pulse dose is sequentially laminated on the surface of the granule or pellet, and each dose is separated by a functional layer coating; the functional layer coating is at least 2 hysteresis layer coatings; wherein the coating material of the hysteresis layer is one or a plurality of combinations of insoluble high molecular polymers and enteric high molecular polymers.
Preferably, the insoluble high molecular polymer is selected from one or more of ethyl cellulose, methacrylic acid copolymer and cellulose acetate; the enteric polymer is one or more selected from Eudragit S100, eudragit L100 and Eudragit L30D-55.
Preferably, the tandospirone citrate 3 pulse release preparation specifically comprises:
(1) The pulse 3 release preparation comprises the components of 10mg of tandospirone citrate, 24mg to 200mg of filler, 5mg to 10mg of disintegrating agent, 0.5mg to 5mg of adhesive, 15mg to 25.0mg of enteric high polymer, 1.0mg to 5mg of triethyl citrate and 0.5mg to 5mg of talcum powder;
(2) The pulse 2 release preparation comprises 100 to 200mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1 to 5mg of adhesive, 10 to 20mg of enteric polymer, 1 to 5mgmg mg of triethyl citrate and 1 to 5mg of talcum powder;
(3) The pulse 1 release preparation consists of 100-300 mg pulse 2 release preparation, 10mg tandospirone citrate and 1-5 mg adhesive.
Preferably, the tandospirone citrate 3 pulse release preparation specifically comprises:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 20mg, triethyl citrate 2mg, and talcum powder 2 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 13.5mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
Preferably, the tandospirone citrate 3 pulse release preparation specifically comprises:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 15mg, triethyl citrate 1.5mg, talcum powder 1.5 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 13.5mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
Preferably, the tandospirone citrate 3 pulse release preparation specifically comprises:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 25mg, triethyl citrate 2.5mg, and talcum powder 2.5 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 16.9mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
The preparation method of the tandospirone citrate pulse preparation adopts an extrusion spheronization method-a fluidized bed coating method to prepare a 3-pulse preparation, and comprises the following specific steps:
(1) Accurately weighing tandospirone citrate, microcrystalline cellulose, lactose and low-substituted hydroxypropyl cellulose, placing in a wet granulator, uniformly mixing, adding hydroxypropyl cellulose solution, preparing a soft material, extruding, rounding, and drying to obtain pulse 3 drug-loaded pellets;
(2) Accurately weighing the Uttky S100 triethyl citrate and talcum powder, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying the mixture onto the surface of the drug-loaded pellets by adopting a WURST bottom spraying coating process to obtain pulse 3 pellets;
(3) Accurately weighing tandospirone citrate and hypromellose, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying the mixture onto the surface of the pulse 3 pellet by adopting WURST bottom spray coating process to obtain a pulse 2 drug-carrying pellet;
(4) Accurately weighing Eudragit L100, triethyl citrate and talcum powder, adding into a proper amount of 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying onto the surface of pulse 2 drug-carrying pellets by adopting WURST bottom spray coating process to obtain pulse 2 pellets;
(5) Accurately weighing tandospirone citrate and hydroxypropyl cellulose, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying the mixture onto the surface of pulse 2 pellets by adopting WURST bottom spray coating process to obtain pulse 1 drug-carrying pellets, and simultaneously obtaining a 3-pulse preparation.
An application of the pulse preparation in the pulse of tandospirone citrate is provided.
Therefore, the tandospirone citrate pulse preparation, the preparation method and the application thereof have the following beneficial effects:
1. The tandospirone citrate pulse preparation provided by the invention is a 3-time pulse release preparation, and is only required to be taken once a day, so that the medication psychological pressure of patients is reduced, and the medication compliance of patients with mental diseases is improved;
2. According to the tandospirone citrate pulse preparation provided by the invention, different functional layer coating materials are selected to be composed according to the detention time of the preparation in different parts/physiological environments in a digestive system so as to ensure the release speed and total dosage of bulk drugs;
3. The tandospirone citrate pulse preparation provided by the invention is a multi-dose preparation, is coated by a hysteresis layer of 3 pulses, is rapidly released after the first pulse enters the gastrointestinal tract, is released after the second pulse dose is released after about 4 hours of time lag, is also subjected to 3-4 hours of time lag (the total time lag time is 7-8 hours) after the third pulse dose is released, thereby achieving the purpose of three times of administration in a day, achieving stable effect in an in vivo environment, avoiding the phenomenon of early or delayed dissolution and effectively ensuring the stability of the blood concentration in a patient;
4. the preparation method of the tandospirone citrate 3 pulse preparation provided by the invention is simple and easy to operate, has low requirements on equipment, and the prepared pulse preparation is suitable in size and easy to swallow.
The technical scheme of the invention is further described in detail through the drawings and the embodiments.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the description of the embodiments of the present invention will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is an in vitro dissolution graph (pH 1.0-pH 6.8-pH 7.2) of pulse 2 pellets+pulse 3 pellets in example I of the present invention;
FIG. 2 is an in vitro dissolution profile (pH 1.0-pH6.8-pH 7.2) of a three-pulse pellet (finished product) in accordance with example one of the present invention.
Detailed Description
The technical scheme of the invention is further described below through the attached drawings and the embodiments.
In order to make the objects, technical solutions and advantages of the present application more clear, thorough and complete, the technical solutions in the embodiments of the present application will be clearly and completely described below through the drawings and the embodiments. The following detailed description is of embodiments, and is intended to provide further details of the application. Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
The instrumentation and reagent materials used in the examples are commercially available.
Example 1
The preparation method of the tandospirone citrate pulse preparation comprises the following steps:
(1) Accurately weighing tandospirone citrate (API), microcrystalline cellulose, lactose and low-substituted hydroxypropyl cellulose according to the data listed in table 1, placing into a wet granulator, uniformly mixing, adding a hydroxypropyl cellulose solution, preparing a soft material, extruding, rounding, and drying to obtain the pulse 3 drug-carrying pellets of prescriptions 1 to 5.
(2) The required amount of Eudragit S100, triethyl citrate and talcum powder are respectively and accurately weighed according to the data listed in the table 1, added into 95% ethanol, stirred until the mixture is dissolved or dispersed uniformly, and sprayed onto the surface of the drug-carrying pellets by adopting a WURST bottom spraying coating process, thus obtaining the pulse 3 pellets of the prescriptions 1 to 5.
Table 1 pulse 3 pellet formulation
Performing a dissolution experiment on the pulse 3 pellets of the prescriptions 1 to 5 obtained in the step (2) by using a dissolution instrument (RCZ-8M, daily onset), wherein the dissolution method comprises the following steps: basket method, 100rpm, dissolution medium is: 900ml of 0.1M hydrochloric acid solution is dissolved for 2 hours, then the solution is transferred into 900ml of phosphate buffer solution with pH of 7.2, the solution is operated for 6 hours, and the cumulative dissolution rate (%) of different detection times is shown in table 2.
Table 2 in vitro dissolution results for prescriptions 1-5 (0.1M hydrochloric acid-pH 7.2, 900mL, N=12)
As can be seen from table 2, when prescription 1, ewing S100, is used in an amount of 10% of the weight of the core of the pill, the drug time lag is only 2 hours, and the target time lag time is not reached; prescription 2 to prescription 4, namely, when the dosage of the Eudragit S100 accounts for 15 to 25 percent of the weight of the pill carrying core, the medicine can be rapidly released after 3 to 4 hours of time lag, and the medicine is completely released within 2 hours; prescription 5, when the amount of the Uttky S100 accounts for 30% of the weight of the drug-carrying pill core, the drug is slowly released after 5 hours, and the release is incomplete.
(3) Accurately weighing the API and the hypromellose according to the data listed in the table 3, adding the API and the hypromellose into 95% ethanol, stirring until the API and the hypromellose are dissolved or dispersed uniformly, and spraying the mixture onto the surface of the prescription 3 pulse 3 pellet prepared in the step (2) by adopting a WURST bottom spraying coating process to obtain the pulse 2 drug-carrying pellet.
(4) The required amount of Eudragit L100, triethyl citrate and talcum powder are respectively and accurately weighed according to the data listed in the table 3, added into 95% ethanol, stirred until the mixture is dissolved or dispersed uniformly, and sprayed onto the surface of pulse 2 drug-carrying pellets by adopting WURST bottom spraying coating technology, thus obtaining the pulse 2 pellets of the prescription 7 and the prescription 8.
Table 3 pulse 2 pellet formulation
| Names of raw and auxiliary materials | Prescription 7 | Prescription 8 |
| Pulse 3 micropill | 124mg | 124mg |
| API | 10mg | 10mg |
| Hydroxypropyl methylcellulose | 1mg | 1mg |
| Pulse 2 pill weight | 135mg | 135mg |
| Uttky L100 | 13.5mg | 16.9mg |
| Citric acid triethyl ester | 2.68mg | 2.68mg |
| Talc powder | 1.34mg | 1.34mg |
| 95% Ethanol | 250ml | 250ml |
| Totals to | 153mg | 156mg |
And (3) carrying out a dissolution experiment on the prescription 7 and prescription 8 pulse 2 pellets obtained in the step (4) by adopting a dissolution instrument (RCZ-8M, heaven and earth, the dissolution method comprises the following steps: basket method, 100rpm, dissolution medium is: stage 1 was 900mL of 0.1M HCl solution and run for 2h; the phase 2 was 900ml of phosphate buffer, pH6.8, run for 4 hours, the phase 3 was 900ml of phosphate buffer, pH7.2, run for 6 hours, and the cumulative dissolution (%) at different test times were as shown in Table 4 and FIG. 1.
Table 4 dissolution data for pulse 2 pellets (0.1M hydrochloric acid-pH 6.8-pH7.2, 900ml, N=12)
As can be seen from the dissolution test results in Table 4 and FIG. 1, when the weight of Eudragit L100 accounts for 10% -12.5% of the weight of the drug-loaded pill, namely, the pulse 2+pulse 3 pellets prepared in the prescription 7 and the prescription 8 are in 0.1M hydrochloric acid-pH 6.8-pH7.2 phosphate buffer, the drug is obviously released by two pulses.
(5) Accurately weighing tandospirone citrate and hydroxypropyl cellulose according to the data listed in table 5, adding the tandospirone citrate and the hydroxypropyl cellulose into 95% ethanol, stirring until the tandospirone citrate and the hydroxypropyl cellulose are dissolved, spraying the tandospirone citrate and the hydroxypropyl cellulose onto the surface of the prescription 7 pulse 2 pellets prepared in the step (4) by adopting a WURST bottom spraying coating process, thus obtaining pulse 1 drug-carrying pellets, and simultaneously obtaining prescription 9 three pulse pellets. And filling the obtained three-time pulse pellets into a No. 2 capsule to obtain a finished product of the tandospirone citrate 3 pulse preparation.
Table 5 three times pulse micropill (finished product)
| Names of raw and auxiliary materials | Prescription 9 |
| Pulse 2 micropill | 153mg |
| Tandospirone citrate | 10mg |
| Hydroxypropyl cellulose | 1mg |
| 95% Ethanol | 10ml |
| Totals to | 164mg |
| Capsule | No. 2 capsule |
And (3) carrying out a dissolution experiment on the prescription 9 (finished product) obtained in the step (5) by adopting a dissolution instrument, wherein the dissolution method comprises the following steps: basket method, 100rpm, dissolution medium is: stage 1 was 900mL of 0.1M HCl, run for 2h; phase 2 was 900mL of phosphate buffer pH6.8, run 4h, phase 3 was 900mL of HCl pH7.2, run 8h to simulate digestion of the tandospirone citrate pulse formulation in the stomach and small intestine. Cumulative dissolution rate (%) at various detection times the detection results are shown in table 6 and fig. 2.
Table 6 in vitro dissolution of three pulse pellets
As can be seen from the experimental results in table 6 and fig. 2, in 0.1M HCl, the drug in pulse 1 portion was substantially completely released within 15min, and neither pulse 2 nor pulse 3 was leaked; pulse 2 part, release after about 3-4 hours, release completely after about 1.5 hours, release after about 8 hours after pulse 3; and the drug release is complete after 3 hours.
Therefore, the tandospirone citrate pulse preparation provided by the invention is a 3-pulse release preparation, and different functional layer coating materials are selected to be composed according to the detention time of the preparation in different parts/physiological environments in a digestive system so as to ensure the release speed and total dosage of bulk drugs; the coating materials with different pulses have stable effects in the in-vivo environment, do not have the phenomenon of early/late dissolution, can effectively ensure the stable blood concentration in the body of a patient, reduce the medication psychological pressure of the patient, and improve the medication compliance of the patient with mental diseases; the prepared pulse preparation has proper size and is easy to swallow.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention and not for limiting it, and although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that: the technical scheme of the invention can be modified or replaced by the same, and the modified technical scheme cannot deviate from the spirit and scope of the technical scheme of the invention.
Claims (8)
1. A tandospirone citrate pulse preparation, characterized in that the tandospirone citrate pulse preparation is a tandospirone citrate 3 pulse release preparation based on a multiparticulate drug delivery system; the multiparticulate drug delivery system is a granule or pellet preparation, each pulse dose is sequentially laminated on the surface of the granule or pellet, and each dose is separated by a functional layer coating; the functional layer coating is at least 2 hysteresis layer coatings; wherein the coating material of the hysteresis layer is one or a plurality of combinations of insoluble high molecular polymers and enteric high molecular polymers.
2. The tandospirone citrate pulse formulation of claim 1, wherein: the insoluble high molecular polymer is one or more selected from ethyl cellulose, methacrylic acid copolymer and cellulose acetate; the enteric polymer is one or more selected from Eudragit S100, eudragit L100 and Eudragit L30D-55.
3. The tandospirone citrate pulse preparation according to claim 2, characterized in that the tandospirone citrate 3 pulse release preparation is specifically:
(1) The pulse 3 release preparation comprises the components of 10mg of tandospirone citrate, 24mg to 200mg of filler, 5mg to 10mg of disintegrating agent, 0.5mg to 5mg of adhesive, 15mg to 25mg of enteric polymer, 1mg to 5mg of triethyl citrate and 0.5mg to 5mg of talcum powder;
(2) The pulse 2 release preparation comprises 100 to 200mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1 to 5mg of adhesive, 10 to 20mg of enteric polymer, 1 to 5mg of triethyl citrate and 1 to 5mg of talcum powder;
(3) The pulse 1 release preparation consists of 100-300 mg pulse 2 release preparation, 10mg tandospirone citrate and 1-5 mg adhesive.
4. A tandospirone citrate pulse formulation according to claim 3, characterized in that said tandospirone citrate 3 pulse release formulation is specifically:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 20mg, triethyl citrate 2mg, and talcum powder 2 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 13.5mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
5. A tandospirone citrate pulse formulation according to claim 3, characterized in that said tandospirone citrate 3 pulse release formulation is specifically:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 15mg, triethyl citrate 1.5mg, talcum powder 1.5 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 13.5mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
6. The tandospirone citrate pulse preparation according to claim 1, wherein the tandospirone citrate 3 pulse release preparation is specifically:
(1) Pulse 3 release preparation comprising tandospirone citrate 10mg, microcrystalline cellulose 70mg, lactose 12.5mg, low substituted hydroxypropyl cellulose 7mg, hydroxypropyl cellulose 0.5mg, eudragit S100 25mg, triethyl citrate 2.5mg, and talcum powder 2.5 mg;
(2) The pulse 2 release preparation comprises 124mg of pulse 3 release preparation, 10mg of tandospirone citrate, 1mg of hypromellose, 16.9mg of Eudragit L100, 2.68mg of triethyl citrate and 1.34mg of talcum powder;
(3) The pulse 1 release preparation comprises 153mg of pulse 2 release preparation, 10mg of tandospirone citrate and 1mg of hydroxypropyl cellulose.
7. A method for preparing a tandospirone citrate pulse preparation according to any one of claims 1 to 6, characterized in that a3 pulse preparation is prepared by adopting an extrusion spheronization method-a fluidized bed coating method, and the specific steps are as follows:
(1) Accurately weighing tandospirone citrate, microcrystalline cellulose, lactose and low-substituted hydroxypropyl cellulose, placing in a wet granulator, uniformly mixing, adding hydroxypropyl cellulose solution, preparing a soft material, extruding, rounding, and drying to obtain pulse 3 drug-loaded pellets;
(2) Accurately weighing Eudragit S100, triethyl citrate and talcum powder, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying onto the surface of drug-loaded micropill by WURST bottom spray coating process to obtain pulse 3 micropill;
(3) Accurately weighing tandospirone citrate and hypromellose, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying the mixture onto the surface of the pulse 3 pellet by adopting WURST bottom spray coating process to obtain a pulse 2 drug-carrying pellet;
(4) Accurately weighing Eudragit L100, triethyl citrate and talcum powder, adding into a proper amount of 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying onto the surface of pulse 2 drug-carrying pellets by adopting WURST bottom spray coating process to obtain pulse 2 pellets;
(5) Accurately weighing tandospirone citrate and hydroxypropyl cellulose, adding into 95% ethanol, stirring until the mixture is dissolved or dispersed uniformly, and spraying the mixture onto the surface of pulse 2 pellets by adopting WURST bottom spray coating process to obtain pulse 1 drug-carrying pellets, thus obtaining the 3 pulse preparation.
8. Use of a pulse preparation as defined in any one of claims 1 to 6 in the pulsing of tandospirone citrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410394239.5A CN118252803A (en) | 2024-04-02 | 2024-04-02 | Tandospirone citrate pulse preparation and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410394239.5A CN118252803A (en) | 2024-04-02 | 2024-04-02 | Tandospirone citrate pulse preparation and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118252803A true CN118252803A (en) | 2024-06-28 |
Family
ID=91609101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410394239.5A Pending CN118252803A (en) | 2024-04-02 | 2024-04-02 | Tandospirone citrate pulse preparation and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118252803A (en) |
-
2024
- 2024-04-02 CN CN202410394239.5A patent/CN118252803A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10973769B2 (en) | Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof | |
| CN107405309B (en) | Modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders | |
| US9801826B2 (en) | Accordion pill comprising levodopa for an improved treatment of Parkinson's Disease symptoms | |
| CN105025886B (en) | The oral preparation of Deferasirox (DEFERASIROX) | |
| CN109044981A (en) | A kind of Pregabalin intragastric floating slowly releasing piece and preparation method thereof | |
| US12128141B1 (en) | Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof | |
| JP5879359B2 (en) | Pharmaceutical compositions comprising citric acid and bicarbonate and their use for treating cystinuria | |
| MD3684344T2 (en) | Delayed release deferiprone tablets and methods of using the same | |
| CN109568284B (en) | Tenofovir alafenamide enteric-coated tablet and preparation method thereof | |
| WO2024160030A1 (en) | Composition and use thereof in preparation of drug for treating neuropathic pain | |
| TW202423472A (en) | Compositions for oral delivery | |
| CN115581686B (en) | Preparation method of pregabalin capsule and pregabalin capsule | |
| JP2008521756A (en) | Novel formulation and preparation method of pyridoxal-5'-phosphate | |
| CN112315934B (en) | Preparation process of pulsatilla saponin B4 enteric-coated tablet | |
| CN117442577B (en) | Candesartan cilexetil microchip and preparation method and application thereof | |
| CN118252803A (en) | Tandospirone citrate pulse preparation and preparation method and application thereof | |
| CN114762682A (en) | Pregabalin sustained release tablet | |
| US20250367137A1 (en) | Phloroglucinol Formulations And Methods Of Use | |
| TWI744858B (en) | Modified release pharmaceutical composition and method for the treatment of mental disorders | |
| WO2024213090A1 (en) | Dual-release preparation and use thereof | |
| CN110974807A (en) | Cetirizine pseudoephedrine sustained-release capsule and preparation method thereof | |
| CN119454626A (en) | A kind of dapagliflozin metformin sustained-release tablets and preparation method thereof | |
| CN121370795A (en) | A method for preparing veliximab sustained-release tablets. | |
| CN105919968A (en) | Topiroxostat preparation and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |