CN109589304A - Risperidone oral administration solution and preparation method thereof - Google Patents
Risperidone oral administration solution and preparation method thereof Download PDFInfo
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- CN109589304A CN109589304A CN201710924607.2A CN201710924607A CN109589304A CN 109589304 A CN109589304 A CN 109589304A CN 201710924607 A CN201710924607 A CN 201710924607A CN 109589304 A CN109589304 A CN 109589304A
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- China
- Prior art keywords
- solution
- risperidone
- oral administration
- oral
- administration solution
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- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960001534 risperidone Drugs 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title abstract description 20
- 239000000463 material Substances 0.000 claims abstract description 12
- 235000003599 food sweetener Nutrition 0.000 claims abstract description 6
- 239000003755 preservative agent Substances 0.000 claims abstract description 6
- 230000002335 preservative effect Effects 0.000 claims abstract description 6
- 239000003765 sweetening agent Substances 0.000 claims abstract description 6
- 239000006174 pH buffer Substances 0.000 claims abstract description 5
- -1 corrigent Substances 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 229940100688 oral solution Drugs 0.000 claims description 8
- 239000004376 Sucralose Substances 0.000 claims description 6
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 6
- 235000019408 sucralose Nutrition 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 claims description 5
- 240000000851 Vaccinium corymbosum Species 0.000 claims description 5
- 235000003095 Vaccinium corymbosum Nutrition 0.000 claims description 5
- 235000017537 Vaccinium myrtillus Nutrition 0.000 claims description 5
- 235000021014 blueberries Nutrition 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 229940048879 dl tartaric acid Drugs 0.000 claims description 5
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 5
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 5
- 239000000796 flavoring agent Substances 0.000 claims description 5
- 235000019634 flavors Nutrition 0.000 claims description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 5
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 5
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 5
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 5
- 229960003415 propylparaben Drugs 0.000 claims description 5
- 229960001367 tartaric acid Drugs 0.000 claims description 5
- 235000002906 tartaric acid Nutrition 0.000 claims description 5
- 239000011975 tartaric acid Substances 0.000 claims description 5
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 235000016623 Fragaria vesca Nutrition 0.000 claims description 4
- 240000009088 Fragaria x ananassa Species 0.000 claims description 4
- 235000011363 Fragaria x ananassa Nutrition 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 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 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 235000005979 Citrus limon Nutrition 0.000 claims description 2
- 244000131522 Citrus pyriformis Species 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 2
- 239000007968 orange flavor Substances 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- 239000002904 solvent Substances 0.000 claims 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 244000269722 Thea sinensis Species 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- 235000009508 confectionery Nutrition 0.000 claims 1
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical compound O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 claims 1
- 230000001934 delay Effects 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 229960003885 sodium benzoate Drugs 0.000 claims 1
- 239000001509 sodium citrate Substances 0.000 claims 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims 1
- 235000011083 sodium citrates Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 10
- 229940072632 risperidone oral solution Drugs 0.000 abstract description 7
- 239000007788 liquid Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000005352 clarification Methods 0.000 abstract 1
- 230000000857 drug effect Effects 0.000 abstract 1
- 230000008595 infiltration Effects 0.000 abstract 1
- 238000001764 infiltration Methods 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000003186 pharmaceutical solution Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 41
- 239000008213 purified water Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000004140 cleaning Methods 0.000 description 5
- 230000001351 cycling effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000005303 weighing Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 101150049660 DRD2 gene Proteins 0.000 description 2
- 230000001133 acceleration Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 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 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropyl alcohol Natural products CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 241000219000 Populus Species 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000009246 food effect Effects 0.000 description 1
- 235000021471 food effect Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012549 training Methods 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to field of pharmaceutical preparations, are related to a kind of Risperidone Oral Solution body preparation.The present invention adds suitable auxiliary material such as pH buffer, corrigent, sweetener, preservative etc. using Risperidone as effective component, is configured to the transparent liquid preparation of achromaticity and clarification using pharmaceutical solutions preparation process.Risperidone Oral Solution body preparation of the invention, drug are dispersed in the medium with molecular state, and infiltration rate is fast, energy fast onset drug effect, convenient to take, are easy to divided dose, can be met the requirements such as clinical application, patient's compliance, industrial-scale production simultaneously.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to a kind of Risperidone Oral Solution and preparation method thereof.
Background technique
This product is phenylpropyl alcohol Isoxazole derivative, is the antipsychotic drug of a new generation.With 5-HT2Receptor and d2 dopamine receptor
There is very high affinity.This product also can be lower with H1 receptor and alpha-2 receptor affinity in conjunction with 1 receptor of α, not with cholinergic recepter
In conjunction with.This product is strong D2 receptor antagonist, can improve schizoid positive symptom；But function is moved caused by it
It can inhibit and catalepsy will be fewer than classical antipsychotic drug.5-HT and dopamine antagonist to cental system make
Balance can reduce the possibility that extrapyramidal side effect occurs, and its therapeutic effect is expanded to schizoid feminine gender
Symptom and affective symptom.This product oral absorption rapidly, completely, absorbs not by food effect, blood medicine is reached after medication 1 hour
Cmax, eliminating half-life period is about 3 hours, and Most patients reached stable state in 1 day.It is partially metabolized as the training of 9- hydroxyl benefit in vivo
Ketone has pharmacological activity, and eliminating half-life period is 24 hours.This product is most of from kidney excretion.Gerontal patient and renal function are not
Full patient's removing speed is slower.
It is listed for the first time in the U.S. within Risperidone 1993, Yuan Yanwei JANSSEN PHARMS, the dosage form that original grinds listing mainly has
Ordinary tablet, oral administration solution, oral disintegrating tablet, injection.
The Risperidone oral administration solution of trade name " Risperidal " is subsidiary-Belgium's Janssen Pharmaceutica by Johson & Johnson
Co., Ltd develops.2002, Risperidal introduced China by the Xi'an Yang Sen company under Johnson & Johnson, in " the dimension of China's sale
Think logical " it is divided into tablet and oral administration solution
Two kinds of dosage forms.Official website, State Food and Drug Administration data information shows that oral solution is by Belgian poplar
Gloomy drugmaker (Janssen Pharmaceutica N.V) production, import registration certificate H20020514, H20120031,
H20120032 is out of date, and existing is national drug standard J20120018, and listing specification has 30mL:30mg, 100mL:
100mg.Currently, domestic many enterprises have obtained the production certification of the oral solid formulations such as Risperidone capsule and tablet, and liquid
In terms of preparation, the Risperidone oral administration solution of domestic unique Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4 is approved to list (national drug standard
H20065005).
Risperidone chemical formula are as follows: 3- [2- [fluoro- 1, the 2- benzo isoxazole -3- base of 4-(6-) -1- piperidyl] ethyl] -6,7,
8,9- tetrahydro -2- methyl -4H- pyrido [1,2- α] pyrimidin-4-ones, molecular formula C23H27FN402, molecular weight 410, chemistry
Structural formula is as follows:
Summary of the invention
The purpose of the present invention is to provide a kind of oral administration solutions and preparation method thereof.It is mainly used for special population, such as: it is old
Year people, child, dysphagia and patient under certain particular surroundings etc., are especially reluctant active medication or are unworthy of sharing
The patient of medicine.
Realize that above-mentioned purpose, technical solution of the present invention are as follows: then heating purified water is added anti-thereto to 60-80 DEG C
Rotten agent, pH buffer, sweetener, stirring to dissolution；Risperidone bulk pharmaceutical chemicals are added after above-mentioned solution is cooling, heat (25-40
DEG C) and stir to dissolution；PH is carried out using prepared sodium hydroxide solution and is adjusted to 2.0-4.0, is eventually adding recipe quantity and is rectified
Taste agent is seasoned, and constant volume.
The corrigent includes but is not limited to: one of orange flavor, orange taste essence, strawberry essence, blueberry flavor.
The sweetener includes but is not limited to: one of sucrose, Sucralose, fructose, lactose are a variety of.
The preservative includes but is not limited to: methyl hydroxybenzoate, ethyl hydroxy benzoate, Nipasol, benzoic acid, in sodium benzoate
It is one or more.
The pH buffer includes but is not limited to: DL- tartaric acid, tartaric acid.
The Risperidone oral administration solution, technology characteristics are that the preparation comprises the steps of:
1, a certain amount of purified water is heated, is heated to 75 DEG C.
2,1mol/L sodium hydroxide solution is prepared: load weighted sodium hydroxide being added in quantitative purified water, is stirred molten
1mol/L sodium hydroxide solution is made in solution, spare.
3, partial purification water is transferred out of from step 1, a portion is used for cleaning container；Remainder purified water is used for
Dissolved material and constant volume.
4, it weighs quantitative purified water and recipe quantity preservative is sufficiently soaked and mixed.
5, recipe quantity preservative, pH buffer, sweetener are added in the container containing hot water, keep heating by temperature
70-80 DEG C is maintained, and being stirred is completely dissolved above-mentioned material.
6, after being completely dissolved, above-mentioned solution is subjected to cooling treatment, its temperature is made to be down to 20-30 DEG C.
7, the Risperidone of recipe quantity is added into solution after cooling, stirring 20-30min makes it dissolve.
8, it adjusts pH value: weighing prepared 1mol/l sodium hydroxide solution, adjust pH value under stiring to 2.5-
4.0。
9, it is eventually adding recipe quantity corrigent, is settled to scale, continues cycling through stirring 20-30min, packing.
Bulk pharmaceutical chemicals physicochemical property of the present invention is clear, absorbs rapidly, bioavilability is high, while oral solution can be patient
Bring mostly a kind of dosage form selection, since Risperidone is that treatment has the drug of mental act abnormal symptom patient, be prepared into take orally it is molten
Liquor is convenient for taking, to increase the compliance of patient.
Embodiment
Below with reference to example, the present invention is described in detail, illustrates the present invention in conjunction with example, but be not limited to
Following embodiments.
Embodiment 1
Composition:
Preparation process:
1, a certain amount of purified water is heated, is heated to 75 DEG C.
2,1mol/l sodium hydroxide solution is prepared: load weighted sodium hydroxide being added in quantitative purified water, is stirred molten
1mol/l sodium hydroxide solution is made in solution.
3, partial purification water is transferred out of from step 1, a portion is used for cleaning container；Remainder purified water is used for
Dissolved material and constant volume.
4, it weighs quantitative purified water sufficiently to dissolve recipe quantity benzoic acid, records experimental phenomena.
5, recipe quantity benzoic acid, tartaric acid, Sucralose are weighed to be added sequentially in the beaker containing hot water, is kept simultaneously
Temperature is maintained 70-80 DEG C by heating, and being stirred is completely dissolved above-mentioned material, judges dissolution situation by range estimation.
6, after being completely dissolved, above-mentioned solution is subjected to cooling treatment, its temperature is made to be down to 20-30 DEG C.
7, the Risperidone bulk pharmaceutical chemicals of recipe quantity are added into solution after cooling, stirring 20-30min makes it dissolve.
8, it adjusts pH value: weighing prepared 1mol/l sodium hydroxide solution, adjust pH value under stiring to 2.5-
4.0。
10, it is eventually adding recipe quantity blueberry flavor, is settled to scale, continues cycling through stirring 20-30min, packing.
Embodiment 2
Composition:
Preparation process:
1, a certain amount of purified water is heated, is heated to 75 DEG C.
2,1mol/l sodium hydroxide solution is prepared: load weighted sodium hydroxide being added in quantitative purified water, is stirred molten
1mol/l sodium hydroxide solution is made in solution.
3, partial purification water is transferred out of from step 1, a portion is used for for cleaning container remainder purified water
Dissolved material and constant volume.
4, it weighs quantitative purified water sufficiently to soak recipe quantity methyl hydroxybenzoate and Nipasol, records experimental phenomena.
5, recipe quantity methyl hydroxybenzoate, Nipasol, DL- tartaric acid, Sucralose is weighed to be added sequentially to containing hot water
In beaker, while keeping heating that temperature is maintained 70-80 DEG C, and being stirred is completely dissolved above-mentioned material, passes through range estimation
Judgement dissolution situation.
6, after being completely dissolved, above-mentioned solution is subjected to cooling treatment, its temperature is made to be down to 20-30 DEG C.
7, the Risperidone bulk pharmaceutical chemicals of recipe quantity are added into solution after cooling, stirring 20-30min makes it dissolve.
8, it adjusts pH value: weighing prepared 1mol/l sodium hydroxide solution, adjust pH value under stiring to 2.5-
4.0。
9, be eventually adding recipe quantity strawberry essence, be settled to scale, continue cycling through stirring 20-30min, by testing requirements into
Row inspection.
Embodiment 3
Composition:
Preparation process:
1, a certain amount of purified water is heated, is heated to 75 DEG C.
2,1mol/l sodium hydroxide solution is prepared: load weighted sodium hydroxide being added in quantitative purified water, is stirred molten
1mol/l sodium hydroxide solution is made in solution.
3, partial purification water is transferred out of from step 1, a portion is used for for cleaning container remainder purified water
Dissolved material and constant volume.
4, it weighs quantitative purified water sufficiently to soak recipe quantity ethyl hydroxy benzoate, records experimental phenomena.
5, it weighs recipe quantity ethyl hydroxy benzoate, DL- tartaric acid, Sucralose to be added sequentially in the beaker containing hot water, together
When keep heating that temperature maintained 70-80 DEG C, and being stirred is completely dissolved above-mentioned material, passes through range estimation judgement dissolution feelings
Condition.
6, after being completely dissolved, above-mentioned solution is subjected to cooling treatment, its temperature is made to be down to 20-30 DEG C.
7, the Risperidone bulk pharmaceutical chemicals of recipe quantity are added into solution after cooling, stirring 20-30min makes it dissolve.
8, it adjusts pH value: weighing prepared 1mol/l sodium hydroxide solution, adjust pH value under stiring to 2.5-
4.0。
9, be eventually adding recipe quantity blueberry flavor, be settled to scale, continue cycling through stirring 20-30min, by testing requirements into
Row inspection.
Embodiment 4
Composition:
Preparation process:
1, a certain amount of purified water is heated, is heated to 75 DEG C.
2,1mol/l sodium hydroxide solution is prepared: load weighted sodium hydroxide being added in quantitative purified water, is stirred molten
1mol/l sodium hydroxide solution is made in solution.
3, partial purification water is transferred out of from step 1, a portion is used for for cleaning container remainder purified water
Dissolved material and constant volume.
4, it weighs quantitative purified water sufficiently to soak recipe quantity sodium benzoate, records experimental phenomena.
5, recipe quantity sodium benzoate, tartaric acid, Sucralose are weighed to be added sequentially in the beaker containing hot water, is protected simultaneously
It holds heating and temperature is maintained 70-80 DEG C, and being stirred is completely dissolved above-mentioned material, dissolution situation is judged by range estimation.
6, after being completely dissolved, above-mentioned solution is subjected to cooling treatment, its temperature is made to be down to 20-30 DEG C.
7, the Risperidone bulk pharmaceutical chemicals of recipe quantity are added into solution after cooling, stirring 20-30min makes it dissolve.
8, it adjusts pH value: weighing prepared 1mol/l sodium hydroxide solution, adjust pH value under stiring to 2.5-
4.0。
9, it is eventually adding recipe quantity lemon extract, is settled to scale, continues cycling through stirring
20-30min, packing.
It is tested according to the influence factor of Risperidone Oral Solution body preparation described in embodiment 1-2.
According to 2015 editions " Chinese Pharmacopoeia " four 9001 bulk pharmaceutical chemicals of guideline and drug preparation stability guideline pair
Risperidone Oral Solution body preparation described in embodiment 1-4 carries out influence factor experiment.Carry out 60 DEG C of high temperature (10 days), -40 DEG C of low temperature
(3 circulation 12 days), -40 DEG C of freeze thawing (3 circulation 12 days), illumination experiment (10 days), take 1-2 sample to carry out influence factor in each condition
Sample setting-out is detected by stability high spot reviews project.It the results are shown in Table 1.
The result shows that: embodiment 1 and 2 prescription of embodiment use prescription provided by the invention and technique, can be made stable
Oral administration solution.
The Acceleration study of Risperidone Oral Solution body preparation described in embodiment 1,2.
According to 2015 editions " Chinese Pharmacopoeia " four 9001 bulk pharmaceutical chemicals of guideline and drug preparation stability guideline pair
Oral liquid described in embodiment 1,2 carries out Acceleration study.Three batches of embodiments 1,2 are respectively taken, are packed by commercially available packaging material is intended,
40 DEG C ± 2 DEG C of temperature, relative humidity be 60% ± 5% under conditions of place 6 months, 1 month during test, 2 months, 3 months,
It is sampled within 6 months, is detected by high spot reviews project.Accelerated test the results are shown in Table 2 and 3.
Embodiment 1,2 accelerated stability tests in 6 months, compared with 0 month, items are checked and are had no significant change, explanation
Embodiment 1, the 2 Risperidone Oral Solution body preparations have good stability, process stabilizing.
Claims (9)
1. a kind of Risperidone oral administration solution, it is characterised in that the solution as made of Risperidone bulk pharmaceutical chemicals and a certain amount of auxiliaries
Agent.
2. Risperidone oral administration solution as described in claim 1, concentration 1mg/ml.
3. the Risperidone oral administration solution as described in any one of claim 1-2, which is characterized in that the oral solution packet
Include preservative, sweetener, corrigent, pH buffer, pH adjusting agent, solvent.
4. Risperidone oral administration solution as claimed in claim 3, which is characterized in that the preservative in the oral solution is benzene
One or more of formic acid, methyl hydroxybenzoate, Nipasol, ethyl hydroxy benzoate, sodium benzoate.
5. Risperidone oral administration solution as claimed in claim 3, which is characterized in that the sweetener in the oral solution is three
Chlorine sucrose.
6. Risperidone oral administration solution as claimed in claim 3, which is characterized in that the corrigent in the oral solution is sweet tea
One of orange essence, blueberry flavor, strawberry essence.
7. Risperidone oral administration solution as claimed in claim 3, which is characterized in that the pH in the oral solution delays agent agent and is
DL- tartaric acid or tartaric acid.
8. Risperidone oral administration solution as claimed in claim 3, which is characterized in that the solvent in the oral solution is purifying
Water.
9. the Risperidone oral administration solution as described in any one of claim 1-8, it is characterised in that common auxiliary material includes but not
It is limited to: sucrose, fructose, Sucralose, sodium hydroxide, DL- tartaric acid, tartaric acid, citric acid, sodium citrate, benzoic acid, benzene first
Sour sodium, methyl hydroxybenzoate, Nipasol, ethyl hydroxy benzoate, strawberry essence, blueberry flavor, orange flavor, lemon extract.
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| CN201710924607.2A CN109589304A (en) | 2017-10-01 | 2017-10-01 | Risperidone oral administration solution and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115381773A (en) * | 2022-09-23 | 2022-11-25 | 南京正科医药股份有限公司 | A kind of risperidone oral liquid |
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| CN103002917A (en) * | 2010-05-31 | 2013-03-27 | 罗维实验室制药股份公司 | Injectable long-acting antipsychotic composition |
| WO2013178812A1 (en) * | 2012-05-31 | 2013-12-05 | Laboratorios Farmacéuticos Rovi, S.A. | Risperidone or paliperidone implant formulation |
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| CN1155247A (en) * | 1994-07-11 | 1997-07-23 | 詹森药业有限公司 | Aqueous risperidone formulations |
| CN1430501A (en) * | 2000-05-25 | 2003-07-16 | 阿尔科米斯控制治疗公司 | Preparation of injectable suspensions having improved injectabity |
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Application publication date: 20190409 |