CN116392447A - Irbesartan dry suspension and preparation method thereof - Google Patents
Irbesartan dry suspension and preparation method thereof Download PDFInfo
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- CN116392447A CN116392447A CN202111683074.6A CN202111683074A CN116392447A CN 116392447 A CN116392447 A CN 116392447A CN 202111683074 A CN202111683074 A CN 202111683074A CN 116392447 A CN116392447 A CN 116392447A
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- 239000002947 C09CA04 - Irbesartan Substances 0.000 title claims abstract description 49
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960002198 irbesartan Drugs 0.000 title claims abstract description 49
- 239000000725 suspension Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000000853 adhesive Substances 0.000 claims abstract description 24
- 230000001070 adhesive effect Effects 0.000 claims abstract description 24
- 238000002156 mixing Methods 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 13
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 11
- 238000004806 packaging method and process Methods 0.000 claims abstract description 11
- 239000004094 surface-active agent Substances 0.000 claims abstract description 11
- 239000000375 suspending agent Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000005303 weighing Methods 0.000 claims abstract description 7
- 238000001035 drying Methods 0.000 claims abstract description 6
- 238000005507 spraying Methods 0.000 claims abstract description 3
- 239000002245 particle Substances 0.000 claims description 20
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 8
- 229930006000 Sucrose Natural products 0.000 claims description 8
- 239000005720 sucrose Substances 0.000 claims description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- 229920002472 Starch Polymers 0.000 claims description 6
- 229960003943 hypromellose Drugs 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
- 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 claims description 4
- 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 4
- 239000000796 flavoring agent Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 238000007873 sieving Methods 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 235000018290 Musa x paradisiaca Nutrition 0.000 claims description 3
- 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 description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 229920000159 gelatin Polymers 0.000 claims description 3
- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 3
- 229920000053 polysorbate 80 Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 229940069328 povidone Drugs 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 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
- 239000008187 granular material Substances 0.000 claims description 2
- 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 229940083542 sodium Drugs 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- 240000005561 Musa balbisiana Species 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 9
- 239000000523 sample Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000005469 granulation Methods 0.000 description 6
- 230000003179 granulation Effects 0.000 description 6
- 239000007919 dispersible tablet Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000005550 wet granulation Methods 0.000 description 5
- 208000019505 Deglutition disease Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000004062 sedimentation Methods 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241000234295 Musa Species 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 239000006191 orally-disintegrating tablet Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- 101150059573 AGTR1 gene Proteins 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 102400000345 Angiotensin-2 Human genes 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009477 fluid bed granulation Methods 0.000 description 1
- 210000002216 heart Anatomy 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
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 230000025033 vasoconstriction Effects 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
- A61K9/1605—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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cardiology (AREA)
Abstract
The invention relates to an irbesartan dry suspension and a preparation method thereof, wherein the dry suspension comprises the following components: 40 to 70 percent of irbesartan, 20 to 50 percent of filler, 0.5 to 3 percent of adhesive, 3 to 15 percent of disintegrating agent, 5 to 20 percent of suspending agent, 0.5 to 3 percent of surfactant, 0.5 to 3 percent of corrigent and 0.1 to 2 percent of lubricant. The preparation method of the dry suspension comprises the following steps: weighing irbesartan, filler, disintegrating agent, surfactant and suspending agent according to the proportion, placing into a fluidized bed mixer-granulator, mixing, spraying into adhesive solution, granulating in one step, drying, granulating, mixing with correctant and lubricant, and packaging according to the set dose. The preparation method disclosed by the invention is simple in production process, and the prepared irbesartan dry suspension is accurate in content, good in dissolution and capable of being rapidly dispersed after being added with water.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an irbesartan dry suspension and a preparation method thereof.
Background
Irbesartan is an angiotensin II (Ang II) receptor antagonist and is used clinically mainly for hypotensive therapy. Irbesartan not only can prevent the process of converting angiotensin I into II, but also can prevent AT1 receptor, inhibit vasoconstriction and release of aldosterone, thereby producing blood pressure lowering effect. The irbesartan has mild antihypertensive effect, is favorable for regulating and controlling glycolipid metabolism, can play a certain role in protecting organs such as heart, kidney, brain and the like, and has a certain preventive and reversing effect when being used for patients with cardiac hypertrophy.
The incidence rate of hypertension in China tends to rise year by year, the hypertension is a long-term chronic disease, life-long treatment is generally required, and middle-aged and elderly patients are in a majority. The currently marketed irbesartan oral preparation is mostly tablets and capsules, the irbesartan tablets are developed by the French Sainophenanthrene company, and are marketed in France in 1997 at the earliest, and have three specifications of 75mg, 150mg and 300mg, and the capsules are modified dosage forms. Tablets and capsules may present dysphagia for the elderly patient population and have poor patient compliance. At present, the existing dispersible tablets and orally disintegrating tablets are marketed, and the dry suspension is not marketed, compared with the dispersible tablets and orally disintegrating tablets, the dry suspension does not need to be pressed into tablets, the preparation process is simple, the phenomenon that the dispersible tablets are dispersed and time-consuming when taken can be avoided, and the dispersible tablets are only taken after being dispersed into the suspension by adding water before taking, so that the compliance of dysphagia patients can be effectively improved.
Disclosure of Invention
The invention aims to provide an irbesartan dry suspension and a preparation method thereof, which can solve the problem of dysphagia of elderly patients, improve the medication compliance of patients, have good taste, have the same in-vitro dissolution rate as a reference preparation (original grinding tablet), and ensure the effectiveness and the safety of products.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the irbesartan dry suspension is prepared from the following components in percentage by weight: 40 to 70 percent of irbesartan, 20 to 50 percent of filler, 0.5 to 3 percent of adhesive, 3 to 15 percent of disintegrating agent, 5 to 20 percent of suspending agent, 0.5 to 3 percent of surfactant, 0.5 to 3 percent of corrigent and 0.1 to 2 percent of lubricant.
Further, the particle size of the irbesartan is less than 30 μm;
further, the filler is one of sucrose, lactose and mannitol, preferably sucrose;
further, the adhesive is one of povidone, hydroxypropyl cellulose and hypromellose, preferably hypromellose;
further, the disintegrating agent is one of crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch, preferably sodium carboxymethyl starch;
further, the suspending agent is one of xanthan gum, hydroxypropyl cellulose, polyvinylpyrrolidone-K30, gelatin, hypromellose and colloidal microcrystalline cellulose, preferably colloidal microcrystalline cellulose;
further, the surfactant is one of Sodium Dodecyl Sulfate (SDS), tween 80 and poloxamer, preferably sodium dodecyl sulfate;
further, the flavoring agent is one of apple essence, orange powder essence and banana essence;
further, the lubricant is one of magnesium stearate, talcum powder and micro powder silica gel, preferably magnesium stearate.
The preparation method of the irbesartan dry suspension adopts the preparation process of granulation, mixing and split charging, and the granulation mode can adopt wet granulation and fluid bed granulation, and specifically comprises the following steps:
s1, taking materials for standby: taking a certain amount of irbesartan, sieving by using a swing granulator, and removing caking for standby; pulverizing filler, and sieving; dissolving the adhesive in water to prepare an adhesive solution with the concentration of 3-8 percent for standby;
s2 granulating: weighing irbesartan, a filling agent, a disintegrating agent, a surfactant and a suspending agent according to the proportion, placing the irbesartan, the filling agent, the disintegrating agent, the surfactant and the suspending agent into a fluidized bed wet mixing granulator, spraying an adhesive solution after mixing, and granulating;
s3, drying: drying the particles obtained in the step S2 by using a fluidized bed to obtain dry particles A, controlling the moisture content of the dry particles A to be less than or equal to 2%, and finishing the particles to obtain dry particles B;
s4, mixing: placing the dry particles B, the flavoring agent and the lubricant into a mixer, and uniformly mixing to obtain particles C;
s5, split charging: and packaging the granules C by using a proper packaging device according to a set dose, wherein the set dose is the same as that of a commercially available tablet, such as 75mg and 150mg.
The beneficial effects of the invention are as follows:
compared with a common tablet, the irbesartan dry suspension is directly taken after being dispersed by water, and is suitable for patients with dysphagia; compared with the dispersible tablet, the preparation process does not need tabletting, can simplify the production process, and saves manpower, time and equipment cost. The dry suspension prepared by the technical scheme of the invention has accurate content, good dissolution, good taste and can be rapidly dispersed into uniform and stable suspension after water is added.
Detailed Description
The present invention is illustrated by the following specific examples, which are not intended to limit the scope of the invention.
The irbesartan dry suspension consists of irbesartan, a filler, an adhesive, a disintegrating agent, a suspending agent, a surfactant and a lubricant, and is prepared by adopting a fluidized bed granulation/wet granulation process, and the specification of the irbesartan dry suspension is consistent with that of tablets on the market.
The following examples are presented to further illustrate the embodiments of the claims and are not intended to limit the scope of the invention.
Example 1:
prescription composition:
the preparation method comprises the following steps:
(1) Taking irbesartan, and using a swing granulator to carry out 60-mesh screening treatment; the sucrose was crushed to a particle size < 100 μm using a universal crusher. The adhesive hydroxypropyl methylcellulose is dissolved in water to prepare an adhesive solution with the concentration of 5 percent for standby.
(2) Irbesartan, sucrose, sodium carboxymethyl starch, SDS and colloidal microcrystalline cellulose are placed in a fluidized bed, mixed uniformly, sprayed into an adhesive solution for granulation, proper parameters are set according to equipment conditions, the materials are dried until the moisture content is less than or equal to 2% after the adhesive solution is sprayed, and then the materials are granulated by a 40-mesh screen.
(3) And (3) placing the dry particles, the orange powder essence and the magnesium stearate into a mixer, and uniformly mixing to obtain the irbesartan dry suspension.
(4) Packaging is performed at a dosage of 150mg using a suitable packaging device.
Example 2:
prescription composition:
the preparation method comprises the following steps:
(1) Taking irbesartan, and using a swing granulator to carry out 60-mesh screening treatment; the sucrose was crushed to a particle size < 100 μm using a universal crusher. The adhesive povidone is dissolved in water to prepare an adhesive solution with the concentration of 5 percent for standby.
(2) Irbesartan, sucrose, sodium carboxymethyl starch, SDS and yellow gelatin are placed in a wet mixing granulator, mixed uniformly, sprayed with an adhesive solution for granulation, wet granulation is carried out by adopting a 40-mesh screen, the wet granulation is carried out by using a fluidized bed for drying until the moisture is less than or equal to 2%, and then the wet granulation is carried out by adopting the 40-mesh screen.
(3) And (3) placing the dry particles, the orange powder essence and the magnesium stearate into a mixer, and uniformly mixing to obtain the irbesartan dry suspension.
(4) Packaging is performed at a dosage of 150mg using a suitable packaging device.
Example 3:
prescription composition:
the preparation method comprises the following steps:
(1) Taking irbesartan and lactose, and using a swing granulator to carry out 60-mesh screening treatment; the adhesive hydroxypropyl cellulose is dissolved in water to prepare an adhesive solution with the concentration of 5 percent for standby.
(2) Irbesartan, lactose, croscarmellose sodium, tween 80 and colloidal microcrystalline cellulose are placed in a fluidized bed, mixed uniformly, sprayed into an adhesive solution for granulation, proper parameters are set according to equipment conditions, the material is dried until the moisture content is less than or equal to 2% after the adhesive solution is sprayed, and then the material is granulated by a 40-mesh screen.
(3) And (3) placing the dry particles, the banana essence and the magnesium stearate into a mixer, and uniformly mixing to obtain the irbesartan dry suspension.
(4) Packaging is performed in a dose of 75mg using a suitable packaging device.
Experiment one: determination of the sedimentation volume ratio
Taking 300mg of irbesartan dry suspension, placing in 50mL of a volumetric flask, adding ultrapure water to 50mL, sealing, shaking forcefully for 1 minute, and recording the starting height H of the suspension 0 Standing for 3 hr, recording final height H of the suspension, and using H/H 0 And calculating the sedimentation volume ratio.
TABLE 1 determination of sedimentation volume ratio
| H0 | H | Sedimentation volume ratio | |
| Example 1 | 49.3 | 48.1 | 0.98 |
| Example 2 | 49.3 | 47.2 | 0.96 |
| Example 3 | 49.6 | 46.1 | 0.93 |
Experiment II: content determination
Taking a proper amount of irbesartan dry suspension, precisely weighing, grinding, precisely weighing a proper amount (about equivalent to 10mg of irbesartan), placing into a 50mL measuring flask, adding a proper amount of methanol, shaking to dissolve and dilute irbesartan to a scale, shaking uniformly, filtering, taking a continuous filtrate as a sample solution, precisely weighing 10 mu L of the sample solution, injecting into a liquid chromatograph, and recording a chromatogram; and precisely weighing a proper amount of irbesartan reference substance, adding methanol for dissolving and quantitatively diluting to prepare a solution containing 0.2mg of irbesartan in 1mL, and determining by the same method. And calculating according to an external standard method and peak area to obtain the product.
Experimental results show that the settling volume ratio of the irbesartan dry suspension prepared by the method is greater than 0.9 (table 1), and the irbesartan dry suspension meets the regulations; the content measurement results are all in the range of 95.0% -105.0% (Table 2), and meet the requirements.
TABLE 2 results of content determination
| Example 1 | Example 2 | Example 3 | |
| Sample 1 | 99.6 | 98.4 | 99.8 |
| Sample 2 | 99.1 | 101.2 | 98.0 |
| Sample 3 | 101.0 | 99.7 | 98.9 |
| Sample 4 | 98.6 | 100.7 | 101.7 |
| Sample 5 | 100.3 | 100.4 | 99.4 |
Experiment III: dissolution Curve determination
Taking a sample, taking 10mL of the solution at 5min, 10min, 15min and 30min by taking 900mL of a 0.1mol/L hydrochloric acid solution as a dissolution medium, performing a paddle method at a rotating speed of 50r/min, filtering, transferring 3mL of the solution into a 50mL volumetric flask (75 mg is placed into a 25mL volumetric flask), fixing the volume to a scale, measuring by an ultraviolet spectrophotometer, detecting the wavelength of 245nm, and calculating the dissolution rate of each sample.
TABLE 3 dissolution test determination results
| Reference formulation 150mg | Example 1 | Example 2 | Reference formulation 75mg | Example 3 | |
| 5min | 39％ | 45％ | 41％ | 52％ | 58％ |
| 10min | 86％ | 89％ | 86％ | 90％ | 92％ |
| 15min | 93％ | 96％ | 94％ | 96％ | 98％ |
| 30min | 96％ | 99％ | 100％ | 98％ | 101％ |
The results show (table 3) that the dissolution rate of the irbesartan dry suspension prepared by the invention is greater than 85% in 10min, and the dissolution rate is equivalent to that of a reference preparation (a sirofirartan tablet).
Claims (3)
1. The irbesartan dry suspension is characterized by being prepared from the following components in percentage by weight: 40 to 70 percent of irbesartan, 20 to 50 percent of filler, 0.5 to 3 percent of adhesive, 3 to 15 percent of disintegrating agent, 5 to 20 percent of suspending agent, 0.5 to 3 percent of surfactant, 0.5 to 3 percent of corrigent and 0.1 to 2 percent of lubricant.
2. An irbesartan dry suspension according to claim 1, wherein:
the filler is one of sucrose, lactose and mannitol, preferably sucrose;
the adhesive is one of povidone, hydroxypropyl cellulose and hypromellose, preferably hypromellose;
the disintegrating agent is one of crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch, preferably sodium carboxymethyl starch;
the suspending agent is one of xanthan gum, hydroxypropyl cellulose, polyvinylpyrrolidone-K30, gelatin, hypromellose and colloidal microcrystalline cellulose, preferably colloidal microcrystalline cellulose;
the surfactant is one of sodium dodecyl sulfate, tween 80 and poloxamer, preferably sodium dodecyl sulfate;
the flavoring agent is one of apple essence, orange powder essence and banana essence;
the lubricant is one of magnesium stearate, talcum powder and micro powder silica gel, preferably magnesium stearate.
3. The preparation method of the irbesartan dry suspension according to claims 1-2, which is characterized by comprising the following steps:
s1, taking materials for standby: taking a certain amount of irbesartan, sieving by using a swing granulator, and removing caking for standby; pulverizing filler, and sieving; dissolving the adhesive in water to prepare an adhesive solution with the concentration of 3-8 percent for standby;
s2 granulating: weighing irbesartan, a filling agent, a disintegrating agent, a surfactant and a suspending agent according to the proportion, placing the irbesartan, the filling agent, the disintegrating agent, the surfactant and the suspending agent into a fluidized bed wet mixing granulator, spraying an adhesive solution after mixing, and granulating;
s3, drying: drying the particles obtained in the step S2 by using a fluidized bed to obtain dry particles A, controlling the moisture content of the dry particles A to be less than or equal to 2%, and finishing the particles to obtain dry particles B;
s4, mixing: placing the dry particles B, the flavoring agent and the lubricant into a mixer, and uniformly mixing to obtain particles C;
s5, split charging: and packaging the granules C by using a proper packaging device according to a set dose, wherein the set dose is the same as that of a commercially available tablet, such as 75mg and 150mg.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202111683074.6A CN116392447A (en) | 2021-12-28 | 2021-12-28 | Irbesartan dry suspension and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111683074.6A CN116392447A (en) | 2021-12-28 | 2021-12-28 | Irbesartan dry suspension and preparation method thereof |
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