CN104873473B - A kind of modified-release tablets of potassium chloride and preparation method thereof - Google Patents
A kind of modified-release tablets of potassium chloride and preparation method thereof Download PDFInfo
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- CN104873473B CN104873473B CN201510335341.9A CN201510335341A CN104873473B CN 104873473 B CN104873473 B CN 104873473B CN 201510335341 A CN201510335341 A CN 201510335341A CN 104873473 B CN104873473 B CN 104873473B
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- potassium chloride
- release
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- sustained
- release pellet
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- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 title claims abstract description 136
- 239000001103 potassium chloride Substances 0.000 title claims abstract description 68
- 235000011164 potassium chloride Nutrition 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 41
- 239000007912 modified release tablet Substances 0.000 title claims abstract description 27
- 238000013268 sustained release Methods 0.000 claims abstract description 52
- 239000012730 sustained-release form Substances 0.000 claims abstract description 52
- 239000008188 pellet Substances 0.000 claims abstract description 48
- 210000002784 stomach Anatomy 0.000 claims abstract description 27
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 24
- 229920000178 Acrylic resin Polymers 0.000 claims abstract description 24
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 12
- 239000004094 surface-active agent Substances 0.000 claims abstract description 10
- 238000003756 stirring Methods 0.000 claims description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 19
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 238000013019 agitation Methods 0.000 claims description 10
- 239000000839 emulsion Substances 0.000 claims description 10
- 230000002045 lasting effect Effects 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 8
- 229940057995 liquid paraffin Drugs 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 7
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 230000001804 emulsifying effect Effects 0.000 claims description 5
- 239000000314 lubricant Substances 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 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 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000011347 resin Substances 0.000 claims description 2
- 229920005989 resin Polymers 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 238000004132 cross linking Methods 0.000 claims 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 28
- 229940079593 drug Drugs 0.000 abstract description 21
- 239000007939 sustained release tablet Substances 0.000 abstract description 11
- 239000003826 tablet Substances 0.000 abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical group CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000003405 delayed action preparation Substances 0.000 description 4
- -1 hydroxy-propyl Chemical group 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 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 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 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 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 235000020985 whole grains Nutrition 0.000 description 2
- QLOKJRIVRGCVIM-UHFFFAOYSA-N 1-[(4-methylsulfanylphenyl)methyl]piperazine Chemical compound C1=CC(SC)=CC=C1CN1CCNCC1 QLOKJRIVRGCVIM-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 208000012904 Bartter disease Diseases 0.000 description 1
- 208000010062 Bartter syndrome Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000208011 Digitalis Species 0.000 description 1
- 206010013554 Diverticulum Diseases 0.000 description 1
- 208000007217 Esophageal Stenosis Diseases 0.000 description 1
- 206010061974 Gastrointestinal obstruction Diseases 0.000 description 1
- 208000010271 Heart Block Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030194 Oesophageal stenosis Diseases 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 239000013563 matrix tablet Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000009928 nephrosis Diseases 0.000 description 1
- 231100001027 nephrosis Toxicity 0.000 description 1
- NCYVXEGFNDZQCU-UHFFFAOYSA-N nikethamide Chemical compound CCN(CC)C(=O)C1=CC=CN=C1 NCYVXEGFNDZQCU-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 208000026775 severe diarrhea Diseases 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical class [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of modified-release tablets of potassium chloride and preparation method thereof, said preparation its formed by sustained release pellet soluble in the stomach, enteric sustained-release pellet and other pharmaceutically acceptable auxiliary material direct tablet compressings, described sustained release pellet soluble in the stomach is made up of potassium chloride, mesoporous carbon, acrylic resin IV and surfactant, and described enteric sustained-release pellet is made up of potassium chloride, mesoporous carbon, acrylic resin I III and surfactant.The sustained release tablets of the present invention have the advantages that insoluble drug release is steady, drug release stability is good, in the absence of phenomenon of burst release.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of sustained release tablets and its system containing potassium chloride
Preparation Method.
Background technology
Potassium chloride is clinical conventional electrolyte balance regulating, and clinical efficacy is definite, is widely used in clinical departments room.With
In treat and prevent a variety of causes (hypoalimentation, vomiting, severe diarrhea, using row potassium diuretics or prolonged application sugar cortex pierce
Hormone and adrenal cortex stimulin, lose potassium nephrosis, Bartter syndromes etc.) caused by hypopotassaemia, also available for the heart,
Frequent, polyphyly premature beat or rapid heart rate are not normal caused by the poisoning by cardiotonic glycoside such as renal edema and digitalis.
It is well known that potassium chloride is irritant to intestines and stomach, Nausea and vomiting, belly is usually caused not to accommodate diarrhoea.Greatly
Weak, weak and feeble, confusion, low blood pressure, dizziness, heart block may be caused during dosage, or even cause death.When
Often occur the signal being poisoned when taking potassium chloride, therefore for the administration that ordinary preparation must be very careful, controlled to reach
Treat purpose, daily 1-2g potassium chloride dosage usually needs to take point 2-6 time, and the compliance of patient is very poor.Therefore, potassium chloride can be examined
Sustained-release preparation is made in worry.Have the sustained release tablets listing of potassium chloride at home, but because potassium chloride water solubility is very good, existing sustained release
Preparation is often difficult to preferably control the release of medicine, often has the generation of phenomenon of burst release, has larger potential risk, such as because prominent
Releasing causes the cation potassium of high local concentrations in gastrointestinal system, causes the symptoms such as gastrointestinal ulceration, bleeding and perforation.In addition,
Existing sustained release tablets belong to individual unit system, when Gastrointestinal Obstruction, esophageal stricture, diverticulum, intestines atonia to intestines and stomach
Stimulation further increase, the state of an illness can be aggravated.
CN103006696B discloses a kind of preparation method of modified-release tablets of potassium chloride, using hydroxypropyl methylcellulose E15 as sustained release
Material prepares sustained release label, is coated with extended release coatings by slow-release material of acrylic resin RS100, acrylic resin RL100, and be coated with
Sugar-coat.
CN102961363B discloses a kind of potassium chloride slow release capsule, and the content of the potassium chloride slow release capsule is sustained release
Micropill, sustained release pellet is by the supplementary material potassium chloride 70~97% of percentage by weight, moulding material 0~10%, and slow-release material 2~
20%, plasticizer 0.5~5% and antiplastering aid 0~10% form.Potassium chloride and moulding material are well mixed, using dry method system
Grain machine, which is prepared into, carries medicine micropill；Then slow-release material, plasticizer and antiplastering aid are prepared by mixing into slow release layer coating solution；Medicine will be carried
Micropill is placed in fluid bed, and the slow release layer coating solution being prepared into is sprayed into fluid bed, will carry medicine micropill according to conventional side
Method is coated, and sustained release pellet is prepared, and sustained release pellet loads capsule, is prepared into product potassium chloride slow release capsule of the present invention.
CN102144985A is related to the formula and technique of Potassium chloride controlled release tablet, using ethyl cellulose, polyvinylpyrrolidine
Ketone, hydroxypropyl methylcellulose etc. are release retarding agent, are pressed in addition with acceptable inert excipient, lubricant, colouring agent in pharmacy
According to certain ratio, label is prepared with suitable technique, then with cellulose acetate and is equipped with suitable coating additive and prepares
The pellicle of label is wrapped up, and drug release path is produced on film, forms monocompartment osmotic pump-type controlled release system, there is provided the zero of potassium chloride
Level release.
The main method for reaching sustained release in the prior art is by matrix diffusion, coating membrane diffusion or the use in conjunction of the two
The diffusion rate of medicine is controlled, so as to reach slow effect.Clinically widely used potassium chloride sustained release preparation include matrix tablet,
Film controlled release tablet, sustained release pellet etc., it is sustained the main or traditional matrix type drug release or film controlling type drug release of releasing mechanism.Matrix type
Drug release heterogeneity be present, prominent incomplete problem of releasing or release the drug easily occur in sustained release tablets.
The content of the invention
In view of the deficiencies in the prior art, it is an object of the invention to provide a kind of insoluble drug release is steady, stability is good, biological
Availability is high, the simple modified-release tablets of potassium chloride of preparation method.
In order to realize the purpose of the present invention, inventor is studied and updated by lot of experiments, is finally obtained as follows
Technical scheme：
A kind of modified-release tablets of potassium chloride, it is by sustained release pellet soluble in the stomach, enteric sustained-release pellet and other pharmaceutically acceptable auxiliary
Material direct tablet compressing forms, and described sustained release pellet soluble in the stomach is 1 by mass ratio:(0.3-0.5):(0.3-0.5):(0.01-0.03)
Potassium chloride, mesoporous carbon, acrylic resin IV and surfactant composition, described enteric sustained-release pellet by mass ratio be 1:
(0.3-0.5):(0.3-0.5):Potassium chloride, mesoporous carbon, acrylic resin I-III and the surfactant group of (0.01-0.03)
Into.
Preferably, modified-release tablets of potassium chloride as described above, the weight of sustained release pellet soluble in the stomach and enteric sustained-release pellet therein
Than for 1:(2-4), preferred weight ratio 1:3.
Preferably, modified-release tablets of potassium chloride as described above, acrylic resin I-III therein are selected from acrylic resin I, third
The one or more of olefin(e) acid resin II and acrylic resin III.
It is further preferred that modified-release tablets of potassium chloride as described above, pharmaceutically acceptable auxiliary material therein includes filling
Agent, disintegrant and lubricant.It is further preferred that described filler is selected from lactose, microcrystalline cellulose, pregelatinized starch and shallow lake
One or more in powder；It is fine that described disintegrant is selected from PVPP, Ac-Di-Sol, low substituted hydroxy-propyl
One or more in dimension element and sodium carboxymethyl starch；Described lubricant is selected from magnesium stearate, silica, stearic acid richness horse
One or more in sour sodium and talcum powder.
It is further preferred that modified-release tablets of potassium chloride as described above, mesoporous carbon therein is specific surface area for 1018~
1058m2/ g, pore volume are 0.51~0.86cm3/ g mesoporous carbon.
Present invention also offers a kind of preparation method of modified-release tablets of potassium chloride, this method comprises the following steps：
(1) preparation of sustained release pellet soluble in the stomach：
1. potassium chloride is dissolved in 0.05-0.2mol/L hydrochloric acid solutions, adds mesoporous carbon and stir, then sequentially add
Acrylic resin IV, surfactant are stirred to being completely dissolved；
2. the mixed liquor 1. prepared is added in atoleine, quickly stirred to emulsification by 1000~1500rpm rotating speed
Uniformly；
3. the emulsion 2. prepared is heated into 100 DEG C under agitation, lasting stirring removes hydrochloric acid, filters, and cleans
Atoleine, dry, obtain sustained release pellet soluble in the stomach；
(2) preparation of enteric sustained-release pellet：
1. potassium chloride is dissolved in saturation ammoniacal liquor, add mesoporous carbon stir, then sequentially add acrylic resin I-
IIIth, surfactant is stirred to being completely dissolved；
2. the mixed solution 1. prepared is added in atoleine, quickly stirred to breast by 1000~1500rpm rotating speed
Change uniform；
3. the emulsion 2. prepared is heated into 100 DEG C under agitation, lasting stirring removes ammoniacal liquor, filters, and cleans
Atoleine, dry, obtain enteric sustained-release pellet；
(3) sustained release pellet soluble in the stomach will be obtained, enteric sustained-release pellet is well mixed with other pharmaceutically acceptable auxiliary materials, press
Piece, produce.
It should be noted that in the preparation method of modified-release tablets of potassium chloride of the present invention, wherein used surface is lived
Property agent is preferably sorbester p17.
Compared with prior art, modified-release tablets of potassium chloride of the present invention can improve the contact area of medicine and intestines and stomach,
Make drug absorption complete, so as to improve bioavilability；Combined, can be obtained preferably by the micropill of several different drug release rates
Rate of releasing drug, insoluble drug release is steady, blood concentration expected from acquirement, and can maintain longer action time, is released now in the absence of prominent
As the adverse reactions such as stimulation to gastric mucosa can be avoided；Its drug release behavior is the multiple micropills composition compound for forming a dosage
Influence, absorption in vivo has good reappearance；Medicine is little affected by the influence of gastric emptying change in vivo, in body
Interior absorption has good reappearance；Micropill has uniform particle sizes, good fluidity, the advantages that being not easy to crush, particularly in micropill
Capsule core surface coatings, sustained release preparation is made, technique is simple, and tablet etc. can be avoided to cause medicine arteries and veins due to being coated uneven
The risk of punching, safety coefficient are high.
Embodiment
Now the preparation process of the present invention and implementation result, but the protection of the present invention are further described by following examples
Scope is not limited to following examples.Those skilled in the art do not depart from scope and done according to the announcement of the present invention
The improvement and modification gone out all should be within protection scope of the present invention.It should be noted that mesoporous carbon used by embodiment
It is that specific surface area is 1018~1058m2/ g, pore volume are 0.51~0.86cm3/ g mesoporous carbon.
Embodiment 1：The preparation of modified-release tablets of potassium chloride
(1) sustained release pellet soluble in the stomach
(2) enteric sustained-release pellet
(3) sustained release tablets
Preparation method：
(1) potassium chloride is dissolved in 0.1mol/L hydrochloric acid solutions, adds mesoporous carbon and stir, add acrylic resin IV
Stirring adds sorbester p17 and stirred to being completely dissolved to being completely dissolved；Mixed solution is added in atoleine, quick stirring to breast
Change uniform；The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes hydrochloric acid solution, filtering, uses hexamethylene
Alkane washing liquid paraffin, dry, obtain potassium chloride sustained release pellet soluble in the stomach.
(2) potassium chloride is dissolved in saturation ammoniacal liquor, adds mesoporous carbon and stir, added acrylic resin I and stir to complete
Fully dissolved, add sorbester p17 and stir to being completely dissolved；Mixed solution is added in atoleine, quick stirring is uniform to emulsifying；
The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes sodium hydroxide solution, filtering, uses hexamethylene
Washing liquid paraffin, dry, obtain potassium chloride enteric sustained-release pellet.
(3) it is the soluble in the stomach of preparation, enteric sustained-release pellet and pregelatinized starch, low-substituted hydroxypropyl cellulose, stearic acid is rich
Horse acid sodium is well mixed, Φ 20 × 9.5mm scrobicula of bonding stampings, control hardness 100-120N or so, is produced.
Embodiment 2：The preparation of modified-release tablets of potassium chloride
(1) sustained release pellet soluble in the stomach
(2) enteric sustained-release pellet
(3) sustained release tablets
Preparation method：
(1) potassium chloride is dissolved in 0.1mol/L hydrochloric acid solutions, adds mesoporous carbon and stir, add acrylic resin IV
Stirring adds sorbester p17 and stirred to being completely dissolved to being completely dissolved；Mixed solution is added in atoleine, quick stirring to breast
Change uniform；The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes hydrochloric acid solution, filtering, uses hexamethylene
Alkane washing liquid paraffin, dry, obtain potassium chloride sustained release pellet soluble in the stomach.
(2) potassium chloride is dissolved in saturation ammoniacal liquor, adds mesoporous carbon and stir, added acrylic resin I and stir to complete
Fully dissolved, add sorbester p17 and stir to being completely dissolved；Mixed solution is added in atoleine, quick stirring is uniform to emulsifying；
The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes sodium hydroxide solution, filtering, uses hexamethylene
Washing liquid paraffin, dry, obtain potassium chloride enteric sustained-release pellet.
(3) the soluble in the stomach of preparation, enteric sustained-release pellet are mixed with microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate
It is even, Φ 20 × 9.5mm scrobicula of bonding stampings, control hardness 100-120N or so, produce.
Embodiment 3：The preparation of modified-release tablets of potassium chloride
(1) sustained release pellet soluble in the stomach
(2) enteric sustained-release pellet
(3) sustained release tablets
Preparation method：
(1) potassium chloride is dissolved in 0.1mol/L hydrochloric acid solutions, adds mesoporous carbon and stir, add acrylic resin IV
Stirring adds sorbester p17 and stirred to being completely dissolved to being completely dissolved；Mixed solution is added in atoleine, quick stirring to breast
Change uniform；The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes hydrochloric acid solution, filtering, uses hexamethylene
Alkane washing liquid paraffin, dry, obtain potassium chloride sustained release pellet soluble in the stomach.
(2) potassium chloride is dissolved in saturation ammoniacal liquor, adds mesoporous carbon and stir, added acrylic resin I and stir to complete
Fully dissolved, add sorbester p17 and stir to being completely dissolved；Mixed solution is added in atoleine, quick stirring is uniform to emulsifying；
The emulsion of preparation is heated to 100 DEG C under agitation, lasting stirring removes sodium hydroxide solution, filtering, uses hexamethylene
Washing liquid paraffin, dry, obtain potassium chloride enteric sustained-release pellet.
(3) the soluble in the stomach of preparation, enteric sustained-release pellet are well mixed with lactose, PVPP, magnesium stearate, Φ 20 ×
9.5mm scrobicula of bonding stampings, control hardness 100-120N or so, are produced.
Comparative example 1：The preparation of modified-release tablets of potassium chloride
Preparation method：
Potassium chloride crushed 100 mesh sieves, is well mixed with microcrystalline cellulose, hydroxypropyl methylcellulose, add alcohol granulation, cross 18
Mesh sieve, 60 DEG C of dryings, 18 mesh sieve whole grains are crossed, add recipe quantity magnesium stearate, be well mixed, Φ 12mm stampings, control hardness
90-110N or so, produce.
Comparative example 2：The preparation of modified-release tablets of potassium chloride
(1) Core formulation
(2) it is coated prescription
Ethyl cellulose 5g
Hydroxypropylcellulose 1g
Ethanol 100g
Preparation method：
Potassium chloride crushed 100 mesh sieves, is well mixed with microcrystalline cellulose, PVP, add 50% alcohol granulation, cross 18 mesh
Sieve, 60 DEG C of dryings, 18 mesh sieve whole grains are crossed, add recipe quantity magnesium stearate, be well mixed, Φ 12mm stampings, control hardness 90-
110N or so, produce label.Ethyl cellulose and hydroxypropylcellulose are dissolved in ethanol, the label of preparation is coated, to weightening
20% or so.
Embodiment 4：The drug release determination of modified-release tablets of potassium chloride
This product is taken, according to drug release determination method (Chinese Pharmacopoeia the second methods of version annex X D in 2010), using dissolution method
Second subtraction unit (Chinese Pharmacopoeia version annex X C in 2010), using 0-2h using pH1.2 hydrochloric acid solutions 500ml as solvent, after 2h samplings
Add warmed-up pH6.8 phosphate buffer solution 400ml, rotating speed is 75 turns per minute, is operated in accordance with the law, during through 1,2,4,6 and 8h,
Solution 25ml is taken respectively, is filtered, and supplements mutually synthermal, same volume dissolution medium in process container immediately；Take continuous filter
Liquid is as need testing solution；Another potassium chloride reference substance is appropriate, and being dissolved in water and diluting is made, and is dissolved in water and quantifies dilution and makes
Into in every lml containing about 80 μ g solution, as reference substance solution.Precision measures need testing solution and takes subsequent filtrate 20mL, adds respectively
Enter potassium chromate indicator 4 to drip, titrated with 0.01mol/L silver nitrates (specification 0.01mol/L, F=1.013), and it is molten using blank
Agent corrects, and drug release determination the results are shown in Table.
Table 1：Modified-release tablets of potassium chloride drug release determination result (%)
It was found from the experiment statisticses result of table 1, modified-release tablets of potassium chloride prepared by embodiment 1-3 is left in 2h releases 25%
The right side, it is primarily due to sustained release pellet soluble in the stomach and is discharged under the conditions of pH1.2 completely, and enteric-coated micro-pill will not be released in acid condition
Put, therefore the sustained release tablets of the present invention are not in phenomenon of burst release；Enteric-coated micro-pill has preferable slow release effect under the conditions of pH6.8,
8h medicines discharge completely substantially.Comparative example 1 is ordinary gel type sustained release tablets, and comparative example 2 is film controlling type sustained release tablets, prominent release be present
Risk, caused result is that each sample release differs greatly during drug release determination.
Claims (6)
1. a kind of preparation method of modified-release tablets of potassium chloride, it is characterised in that this method comprises the following steps：
（1）The preparation of sustained release pellet soluble in the stomach：
1. potassium chloride is dissolved in 0.05-0.2mol/L hydrochloric acid solutions, adds mesoporous carbon and stir, then sequentially add propylene
Acid resin IV, surfactant are stirred to being completely dissolved；
2. the mixed liquor 1. prepared is added in atoleine, quickly stirred by 1000~1500rpm rotating speed uniform to emulsifying；
3. the emulsion 2. prepared is heated into 100 DEG C under agitation, lasting stirring removes hydrochloric acid, filtering, washing liquid
Paraffin, dry, obtain sustained release pellet soluble in the stomach；
（2）The preparation of enteric sustained-release pellet：
1. potassium chloride is dissolved in saturation ammoniacal liquor, adds mesoporous carbon and stir, then sequentially add acrylic resin I-III, table
Face activating agent is stirred to being completely dissolved；
2. the mixed solution 1. prepared is added in atoleine, quickly stirred by 1000~1500rpm rotating speed equal to emulsifying
It is even；
3. the emulsion 2. prepared is heated into 100 DEG C under agitation, lasting stirring removes ammoniacal liquor, filtering, washing liquid
Paraffin, dry, obtain enteric sustained-release pellet；
（3）Sustained release pellet soluble in the stomach will be obtained, enteric sustained-release pellet is well mixed with other pharmaceutically acceptable auxiliary materials, tabletting,
Produce；
Described sustained release pellet soluble in the stomach is 1 by mass ratio:（0.3-0.5）:（0.3-0.5）:（0.01-0.03）Potassium chloride, be situated between
Hole carbon, acrylic resin IV and surfactant composition, described enteric sustained-release pellet are 1 by mass ratio:（0.3-0.5）:
（0.3-0.5）:（0.01-0.03）Potassium chloride, mesoporous carbon, acrylic resin I-III and surfactant composition, described stomach
The weight ratio of molten sustained release pellet and enteric sustained-release pellet is 1:（2-4）, described mesoporous carbon is specific surface area for 1018~
1058m2/ g, pore volume are 0.51~0.86cm3/ g mesoporous carbon.
2. the preparation method of modified-release tablets of potassium chloride according to claim 1, it is characterised in that described surfactant is department
Disk 80.
3. the preparation method of modified-release tablets of potassium chloride according to claim 1, it is characterised in that described sustained release pellet soluble in the stomach with
The weight ratio of enteric sustained-release pellet is 1:3.
4. the preparation method of modified-release tablets of potassium chloride according to claim 1, it is characterised in that described acrylic resin I-III
One or more selected from acrylic resin I, acrylic resin II and acrylic resin III.
5. the preparation method of modified-release tablets of potassium chloride according to claim 1, it is characterised in that described is pharmaceutically acceptable
Auxiliary material includes filler, disintegrant and lubricant.
6. the preparation method of modified-release tablets of potassium chloride according to claim 5, it is characterised in that described filler is selected from breast
One or more in sugar, microcrystalline cellulose, pregelatinized starch and starch；Described disintegrant is selected from PVPP, crosslinking
One or more in sodium carboxymethylcellulose, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch；Described lubricant choosing
One or more from magnesium stearate, silica, sodium stearyl fumarate and talcum powder.
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| CN105250239B (en) * | 2015-11-16 | 2018-09-18 | 遵义医学院 | Ginkgolides nanometer delays controlled release oral dosage formulations and preparation method thereof |
| CN107252418B (en) * | 2017-05-17 | 2020-06-23 | 西安棣加生物科技有限公司 | A method of preparing oral fast disintegrating tablets for the treatment of hypokalemia by 3D printing technology |
| CN107823189B (en) * | 2017-11-25 | 2021-04-06 | 杭州高成生物营养技术有限公司 | Potassium chloride sustained-release pellet and preparation method and application thereof |
| CN110755399A (en) * | 2019-10-29 | 2020-02-07 | 白喜平 | Potassium chloride sustained-release tablet and preparation method thereof |
| CN115554258B (en) * | 2022-10-09 | 2023-07-25 | 广州誉东健康制药有限公司 | Preparation equipment and preparation method of oral potassium chloride sustained release tablet |
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| CN102144985A (en) * | 2011-03-31 | 2011-08-10 | 中国科学院上海药物研究所 | Potassium chloride elementary osmotic pump controlled release tablet and preparation method thereof |
| CN102961363A (en) * | 2012-12-14 | 2013-03-13 | 河南中帅医药科技发展有限公司 | Potassium chloride slow release capsule |
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| CN102144985A (en) * | 2011-03-31 | 2011-08-10 | 中国科学院上海药物研究所 | Potassium chloride elementary osmotic pump controlled release tablet and preparation method thereof |
| CN102961363A (en) * | 2012-12-14 | 2013-03-13 | 河南中帅医药科技发展有限公司 | Potassium chloride slow release capsule |
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Inventor after: Chen Wei Inventor after: Chen Zhenhua Inventor after: Lu Qin Inventor after: Luo Xiaomin Inventor after: Wang Chengying Inventor after: Liang Yue Inventor after: Liu Yanan Inventor after: Zou Xianbao Inventor before: Sun Qiaoling |
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Denomination of invention: The invention relates to a potassium chloride sustained-release tablet and a preparation method thereof Effective date of registration: 20220301 Granted publication date: 20171201 Pledgee: Shenzhen high tech investment and financing Company limited by guarantee Pledgor: SHENZHEN ZHONGLIAN PHARMACEUTICAL CO.,LTD. Registration number: Y2022980002008 |
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