CN109498556A - Aripiprazole oral solution and preparation method thereof - Google Patents
Aripiprazole oral solution and preparation method thereof Download PDFInfo
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- CN109498556A CN109498556A CN201710830227.2A CN201710830227A CN109498556A CN 109498556 A CN109498556 A CN 109498556A CN 201710830227 A CN201710830227 A CN 201710830227A CN 109498556 A CN109498556 A CN 109498556A
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- solution
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- aripiprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of Aripiprazole oral solutions and preparation method thereof.The Aripiprazole oral solution is made of Aripiprazole, preservative, solvent, stabilizer, corrigent, pH buffer, sweetener.The preparation method includes following basic step: sweetener, stabilizer corrigent are dissolved in pure water preparation water phase；Preservative, pH adjusting agent, bulk pharmaceutical chemicals are dissolved in the multi-solvent mixed system organic phase kept the temperature in advance, use pH adjusting agent to adjust pH to 2.5-3.0 after mixing organic phase liquid compatible with water, with pure water constant volume to get Aripiprazole oral solution.
Description
Technical field
The invention belongs to pharmaceutical fields, and in particular to a kind of Aripiprazole oral solution and preparation method thereof.
Background technique
Aripiprazole is first and the dopamine partial agonists that uniquely list in the world.Aripiprazole can adjust more
Bar amine level but incomplete block d2 dopamine receptor, thus to schizophrenia is positive and negative symptoms it is aobvious effectively, and safety
Property is more preferable, and side reaction is less.In addition, clinical data also indicates that, Aripiprazole is to the horizontal shadow such as glucose, weight and lactogen
Sound is little, so being beneficial to improve the compliance of patient tolerability and long-term administration.
It is listed in Japan within Aripiprazole oral solution 2002, Yuan Yanwei Otsuka, the dosage form that original grinds listing mainly has general
Logical piece, oral administration solution.Original grinds and does not enter China temporarily, and the existing ordinary tablet listing in the country is temporarily listed without oral administration solution.
Aripiprazole chemical formula are as follows: 7- { 4- [4- (2,3- dichlorophenyl)-l- piperazinyl] butoxy } -3,4- dihydro -2
(1H)-quinolinone, molecular formula C23H27N302Cl2, molecular weight 448, chemical structure 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 mismatch medication
Patient.
Realize that above-mentioned purpose, technical solution of the present invention are as follows:
The invention discloses a kind of Aripiprazole oral solution preparation method, concrete schemes: by sucrose, fructose or lactose, according to ground
Acid disodium is dissolved in pure water preparation water phase；Methyl hydroxybenzoate, Nipasol or ethyl hydroxy benzoate, Aripiprazole are dissolved in keep the temperature in advance it is sweet
Oil is with propylene glycol, the three-dimensional hybrid system organic phase of lactic acid, and after mixing by organic phase liquid compatible with water finally, use is pure
Water is settled to close at scale, pH buffer is added, pH to 2.5-3.0 is adjusted, be finally settled to scale using pure water, i.e.,
Obtain Aripiprazole oral solution.
The corrigent includes but is not limited to: one of orange taste essence, strawberry essence, blueberry flavor.
The sweetener includes but is not limited to: one of sucrose, fructose, lactose are a variety of.The sweetener packet
Include but be not limited to: one of sucrose, fructose, lactose are a variety of.
The stabilizer includes but is not limited to: natrium adetate.
The Aripiprazole oral solution, which is characterized in that the preparation comprises the steps of:
(1) prepared by organic phase
A, glycerol and propylene glycol are kept the temperature in water-bath, obtains solution 1；
B, preservative is dissolved in solution 1, stirring and dissolving, obtains solution 2；
C, pH adjusting agent is added in solution 2, stirs evenly, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, sweetener is added in appropriate pure water, heating stirring obtains solution 5 to dissolving；
F, natrium adetate and essence are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
Bulk pharmaceutical chemicals physicochemical property of the present invention is clear, absorbs rapidly, and bioavilability is high, be administered simultaneously dosage it is accurate, rationally,
Safety, health, conveniently, it is in good taste, it is easy to old age, child, specific group patient take, is easy the receiving of passive administered patient.
Embodiment
Below with reference to example, the present invention is described in detail
The present invention is illustrated in conjunction with example, but is not limited to following embodiments.
Embodiment 1
Composition:
Preparation process:
(1) prepared by organic phase
A, glycerol and propylene glycol are kept the temperature into 10min in 50 DEG C of water-baths, obtains solution 1；
B, ethyl hydroxy benzoate is dissolved in solution 1, is uniformly mixed, obtains solution 2；
C, DL-LACTIC ACID is added in solution 2, is uniformly mixed, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, lactose is added in appropriate (30%) pure water, heating stirring obtains solution 5 to dissolving；
F, natrium adetate and orange taste essence are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
Embodiment 2
Composition:
Preparation process:
(1) prepared by organic phase
A, glycerol and propylene glycol are kept the temperature into 10min in 50 DEG C of water-baths, obtains solution 1；
B, methyl hydroxybenzoate, Nipasol are dissolved in solution 1, are uniformly mixed, obtain solution 2；
C, lactic acid is added in solution 2, is uniformly mixed, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, lactose is added in appropriate (30%) pure water, heating stirring obtains solution 5 to dissolving；
F, natrium adetate and strawberry essence are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
Embodiment 3
Composition:
Preparation process:
(1) prepared by organic phase
A, glycerol and propylene glycol are kept the temperature into 10min in 50 DEG C of water-baths, obtains solution 1；
B, methyl hydroxybenzoate, Nipasol are dissolved in solution 1, are uniformly mixed, obtain solution 2；
C, lactic acid is added in solution 2, is uniformly mixed, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, sucrose, fructose are added in appropriate (30%) pure water, heating stirring obtains solution 5 to dissolving；
F, natrium adetate and blueberry flavor are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
Embodiment 4
Composition:
Preparation process:
(1) prepared by organic phase
A, glycerol and propylene glycol are kept the temperature into 10min in 50 DEG C of water-baths, obtains solution 1；
B, methyl hydroxybenzoate, Nipasol are dissolved in solution 1, are uniformly mixed, obtain solution 2；
C, DL-LACTIC ACID is added in solution 2, is uniformly mixed, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, sucrose, fructose are added in appropriate (30%) pure water, heating stirring obtains solution 5 to dissolving；
F, natrium adetate and strawberry essence are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
Physicochemical property and mouthfeel are investigated:
1 embodiment 1-4 physicochemical property of table and mouthfeel investigate result
。
By physicochemical result it is found that the Aripiprazole oral solution good fluidity of embodiment 1-4, can preferably produce
Filling and patient takes, and different essence and sweetener are smaller on mouthfeel influence, whole good in taste, without bad mouthfeel, improves
Patient medication compliance.
Claims (7)
1. Aripiprazole oral solution, it is characterised in that the oral administration solution preparation step mainly includes organic phase preparation and water
Mutually prepare:
(1) prepared by organic phase
A, solvent is kept the temperature to 10-20min in water-bath, obtains solution 1；
B, preservative is dissolved in solution 1, stirring and dissolving, obtains solution 2；
C, pH adjusting agent is added in solution 2, stirs evenly, obtains solution 3；
D, bulk pharmaceutical chemicals are added in solution 3, stirring and dissolving, and be uniformly mixed, obtain solution 4；
(2) prepared by water phase
E, sweetener is added in appropriate pure water, heating stirring obtains solution 5 to dissolving；
F, stabilizer and corrigent are added in solution 5, are uniformly mixed, obtain solution 6；
(3) solution 6 is uniformly mixed with solution 4, stands and removes bubble, purified water is settled to close at scale, is buffered using pH
Scale is settled to get Aripiprazole oral solution with pure water after agent adjusting pH to 2.5-3.0.
2. the preparation method of Aripiprazole oral solution according to claim 1, it is characterised in that the stabilizer is
Natrium adetate.
3. the preparation method of Aripiprazole oral solution described in any one of -2 according to claim 1, it is characterised in that institute
The corrigent stated is one of orange taste essence, strawberry essence or blueberry flavor.
4. the preparation method of Aripiprazole oral solution described in any one of -4 according to claim 1, it is characterised in that institute
The sweetener stated is one or more of sucrose, fructose or lactose.
5. the preparation method of the Aripiprazole oral solution according to any one of right 1-3, it is characterised in that described
PH adjusting agent is that a certain kind of lactic acid, DL-LACTIC ACID or its hydrate and sodium hydroxide form.
6. Aripiprazole oral solution described in any one of -5 according to claim 1, it is characterised in that the solvent is
One of glycerol, propylene glycol, pure water are a variety of.
7. Aripiprazole oral solution described in any one of -6 according to claim 1, it is characterised in that the preservative
It is used in combination for one or more of methyl hydroxybenzoate, Nipasol or ethyl hydroxy benzoate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710830227.2A CN109498556A (en) | 2017-09-15 | 2017-09-15 | Aripiprazole oral solution and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710830227.2A CN109498556A (en) | 2017-09-15 | 2017-09-15 | Aripiprazole oral solution and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109498556A true CN109498556A (en) | 2019-03-22 |
Family
ID=65744584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710830227.2A Pending CN109498556A (en) | 2017-09-15 | 2017-09-15 | Aripiprazole oral solution and preparation method thereof |
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| Country | Link |
|---|---|
| CN (1) | CN109498556A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5006528A (en) * | 1988-10-31 | 1991-04-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
| CN1512884A (en) * | 2001-04-25 | 2004-07-14 | ����˹�ж�-����˹˹������˾ | Aripiprazole oral solution |
| CN103393594A (en) * | 2013-08-22 | 2013-11-20 | 万特制药(海南)有限公司 | Novel aripiprazole preparation composition |
| CN104271120A (en) * | 2012-04-30 | 2015-01-07 | 大塚制药株式会社 | Oral formulation |
| CN105616344A (en) * | 2016-01-06 | 2016-06-01 | 万全万特制药江苏有限公司 | Aripiprazole injection and preparation method therefor |
| CN106389343A (en) * | 2016-09-24 | 2017-02-15 | 万全万特制药江苏有限公司 | Oral aripiprazole liquid dry suspension agent and preparation method thereof |
| CN106539752A (en) * | 2015-09-18 | 2017-03-29 | 成都康弘药业集团股份有限公司 | A kind of oral administration solution containing Aripiprazole and preparation method thereof |
-
2017
- 2017-09-15 CN CN201710830227.2A patent/CN109498556A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5006528A (en) * | 1988-10-31 | 1991-04-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
| CN1512884A (en) * | 2001-04-25 | 2004-07-14 | ����˹�ж�-����˹˹������˾ | Aripiprazole oral solution |
| CN104271120A (en) * | 2012-04-30 | 2015-01-07 | 大塚制药株式会社 | Oral formulation |
| CN103393594A (en) * | 2013-08-22 | 2013-11-20 | 万特制药(海南)有限公司 | Novel aripiprazole preparation composition |
| CN106539752A (en) * | 2015-09-18 | 2017-03-29 | 成都康弘药业集团股份有限公司 | A kind of oral administration solution containing Aripiprazole and preparation method thereof |
| CN105616344A (en) * | 2016-01-06 | 2016-06-01 | 万全万特制药江苏有限公司 | Aripiprazole injection and preparation method therefor |
| CN106389343A (en) * | 2016-09-24 | 2017-02-15 | 万全万特制药江苏有限公司 | Oral aripiprazole liquid dry suspension agent and preparation method thereof |
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Application publication date: 20190322 |
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