CN106511264A - Methylphenidate hydrochloride oral solution and preparation method thereof - Google Patents
Methylphenidate hydrochloride oral solution and preparation method thereof Download PDFInfo
- Publication number
- CN106511264A CN106511264A CN201611003081.6A CN201611003081A CN106511264A CN 106511264 A CN106511264 A CN 106511264A CN 201611003081 A CN201611003081 A CN 201611003081A CN 106511264 A CN106511264 A CN 106511264A
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- CN
- China
- Prior art keywords
- oral solution
- methylphenidate hydrochloride
- solution
- agent
- hydrochloride oral
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
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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
- A61K9/08—Solutions
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4458—Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
-
- 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
Abstract
The invention belongs to the technical field of medicines and relates to a methylphenidate hydrochloride oral solution and a preparation method thereof. The methylphenidate hydrochloride oral solution can be used for treating diseases such as attention deficit hyperactivity disorder (childhood hyperkinetic syndrome, minimal brain dysfunction), narcolepsy and coma caused by excess dosage of central depressant drugs including barbitalum and chloral hydrate and the like. The methylphenidate hydrochloride oral solution comprises medicinal auxiliary materials such as methylphenidate hydrochloride, antioxidants, pH regulators, corrigents, preservatives and stabilizers and the like. Through the oral solution provided by the invention, the problem that young and old patients with poor swallowing ability difficultly take medicines are solved; the oral solution has the advantages of suitability for children medication, convenient administration and rapid absorption speed; meanwhile, the oral solution is simple in process, controllable in quality, convenient to take, high in stability and good in taste, and can better meet the clinical requirement.
Description
Technical field
The present invention relates to a kind of pharmacy oral solution preparation technique field, and in particular to methylphenidate hydrochloride oral solution
And preparation method thereof.Methylphenidate hydrochloride is used for treating attention deficit hyperactivity disorder in oral liquid as active component
The central depressants such as (hyperkinetic syndrome, slight brain function imbalance), narcolepsy, and barbiturateses, chloral hydrate
The diseases such as the stupor for excessively causing.
Background technology
Methylphenidate hydrochloride (Methylphenidate Hydrochloride) is α-phenyl -2- piperidineacetate hydrochloric acid
Salt, which can promote Monoamines release by neuron before the prominent place of blocking to norepinephrine and the reuptake of dopamine
To the neuron external space.Methylphenidate is central stimulantss, directly excitement medulla oblongata respiratory center, and effect is relatively gentle, for treating note
Obstacle (hyperkinetic syndrome, slight brain function imbalance), narcolepsy, and barbiturateses, hydration chlorine are moved meaning defect more
The diseases such as the stupor that the CNS inhibition drug overdose such as aldehyde causes.
Methylphenidate hydrochloride absorbs rapid, is grown up after oral this product, and methylphenidate plasma concentration is raised rapidly, in 1-2 hours
Reach original maximum, steadily raise in coming hours, 6-8 hours reach peak plasma concentration, then its plasma concentration start by
Gradually decline.This product without obvious drug accumulation, it is oral after, the plasma concentration of methylphenidate of being grown up is declined in the form of secondary power, is partly declined
About 3.5 hours phase.In human body, methylphenidate is mainly metabolized as α-phenyl-piperidines acetic acid by deesterify effect, and metabolite is several
Parmacodynamics-less activity.90% medicine Jing homalurias, in urine, main metabolite is α-phenyl-piperidines acetic acid, accounts for the 80% of dosage.
The domestic dosage form for selection of clinical has conventional tablet, slow releasing tablet, injection to methylphenidate hydrochloride at present.FDA ratifies
The dosage form of listing has slow releasing capsule, conventional tablet, slow releasing tablet, oral solution, chewable tablet.The volume of tablet is larger,
Be not suitable for the weaker youth of swallow and old people takes.Although injection can solve the problem that the weaker patient of swallow takes
Difficult problem, but due to injection pain, patient's poor compliance.Oral solution good mouthfeel, is particularly suited for swallowing tired
Difficult patient, drug effect are fast.Gastrointestinal tract is flowed through with the form of liquid after oral, accelerates the dissolution rate of medicine, be distributed in human body
Area is big, absorbs point many, it is possible to increase bioavailability, for young and old people and hardly possible change the patient of position, orally
Solution greatly improves the compliance of patient without the need for need not also be chewed with water, improves the effectiveness of clinic and meets an urgent need
Property, for the patient of long term administration treatment is more prone to receive oral solution.
The content of the invention
It is an object of the invention to provide a kind of preparation process is simple, low cost, taking convenience, rapid-action methylphenidate hydrochloride
Oral solution.
Methylphenidate hydrochloride oral solution prescription composition of the present invention includes methylphenidate hydrochloride, antioxidant, correctivess, pH regulator
Agent, stabilizer, preservative.
Methylphenidate hydrochloride oral solution prescription composition of the present invention is preferably：Methylphenidate hydrochloride, antioxidant (0.01% ~ 0.1%),
Correctivess（10%~40%）, pH adjusting agent（2%~8%）, stabilizer (10% ~ 30%), preservative（0.01%~5%）Deng pharmaceutic adjuvant.
Wherein antioxidant includes the mixture of one or more of Vitamin E, BHA, BHT, disodium edetate.Correctivess are selected
From sucrose, Sorbitol, saccharin sodium, stevioside, fragrant citrus essence, apple essence, strawberry essence etc. it is therein one or more.PH regulator
Agent one kind or its mixture or pharmaceutically acceptable other buffer solution bodies in tartaric acid, citric acid, sodium dihydrogen phosphate
System.One or several mixing of the preservative in sodium benzoate, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben etc.
Thing.One or more mixture of the stabilizer in glycerol, Propylene Glycol or Macrogol 1450.PH scopes are between 4.0-6.0.
The preparation method of methylphenidate hydrochloride oral solution of the present invention is：
1）By a certain amount of pure water, principal agent, stabilizer, correctivess are added（Sweeting agent）Preservative, antioxidant, slight fever stirring have made
CL, is cooled to room temperature standby；
2）PH adjusting agent is added into above-mentioned solution into, stirring and dissolving is uniform, filter and add that pure water to population of samples is accumulated 90%；
3）Correctivess are added in above-mentioned solution（Aromatic）, continue to stir, appropriate pure water added after filtration to quantitative.
Methylphenidate hydrochloride oral administration solution, stable in properties, taking convenience, good mouthfeel obtained in of the invention.Below by way of specific
Embodiment is further described to the present invention.These embodiments are merely illustrative, and should not be construed as limiting the invention.
Specific embodiment
Embodiment 1
Methylphenidate hydrochloride 20g
EDTA-2Na 5g
Anhydrous citric acid 10g
Sodium citrate 200g
Sodium benzoate 300g
Glycerol 90kg
PEG1450 10 kg
Fragrant citrus essence 1.0g
Sucrose 8.5kg
Add water to 10L
Preparation technology:
1）By a certain amount of pure water, methylphenidate hydrochloride, glycerol, PEG1450, sucrose, sodium benzoate, EDTA-2Na are added, slight fever is simultaneously
Stirring makes to be completely dissolved, and is cooled to room temperature standby；
2）Add above-mentioned solution into anhydrous citric acid, sodium citrate, stirring and dissolving is uniform, filters and add pure water to sample
The 90% of cumulative volume；
3）Fragrant citrus essence is added in above-mentioned solution, continues to stir, appropriate pure water is added after filtration to quantitative.
Embodiment 2
Methylphenidate hydrochloride 20g
Vitamin E 15g
Anhydrous citric acid 10g
Sodium citrate 200g
Ethyl hydroxybenzoate 250g
Glycerol 90g
PEG1450 10g
Apple essence 1.5g
Sorbitol 8.5kg
Add water to 10L
Preparation technology:
1）By a certain amount of pure water, methylphenidate hydrochloride, glycerol, PEG1450, Sorbitol, ethyl hydroxybenzoate, Vitamin E, slight fever are added
And stirring makes to be completely dissolved, and is cooled to room temperature standby；
2）Add above-mentioned solution into anhydrous citric acid, sodium citrate, stirring and dissolving is uniform, filters and add pure water to sample
The 90% of cumulative volume；
3）Apple essence is added in above-mentioned solution, continues to stir, appropriate pure water is added after filtration to quantitative.
Embodiment 3
Methylphenidate hydrochloride 20g
EDTA-2Na 10g
Sodium dihydrogen phosphate 40g
Disodium hydrogen phosphate 250g
Ethyl hydroxybenzoate 200g
Glycerol 80g
PEG1450 10g
Strawberry essence 2g
Sucrose 8.5kg
Add water to 10L
Preparation technology:
1）By a certain amount of pure water, methylphenidate hydrochloride, glycerol, PEG1450, sucrose, ethyl hydroxybenzoate, EDTA-2Na, slight fever are added
And stirring makes to be completely dissolved, and is cooled to room temperature standby；
2）Add above-mentioned solution into sodium dihydrogen phosphate, disodium hydrogen phosphate, stirring and dissolving is uniform, filters and add pure water to sample
The 90% of product cumulative volume；
3）Strawberry essence is added in above-mentioned solution, continues to stir, appropriate pure water is added after filtration to quantitative.
Embodiment 4
Methylphenidate hydrochloride 20g
EDTA-2Na 10g
Anhydrous citric acid 10g
Sodium citrate 200g
Sodium benzoate 300g
Propylene Glycol 10g
Glycerol 70g
PEG1450 10g
2 g of strawberry essence
Sucrose 8.5kg
Add water to 10L
Preparation technology:
1）By a certain amount of pure water, methylphenidate hydrochloride, Propylene Glycol, glycerol, PEG1450, sucrose, sodium benzoate, EDTA-2Na are added,
Slight fever and stirring make to be completely dissolved, be cooled to room temperature standby；
2）Add above-mentioned solution into anhydrous citric acid, sodium citrate, stirring and dissolving is uniform, filters and add pure water to sample
The 90% of cumulative volume；
3）Strawberry essence is added in above-mentioned solution, continues to stir, appropriate pure water is added after filtration to quantitative.
The mouthfeel and clarity result of the methylphenidate hydrochloride oral solution under different embodiments：
Methylphenidate hydrochloride oral solution mouthfeel and clarity result
。
The above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not to the present invention
Embodiment restriction, to those of ordinary skill in the art, other can also be made on the basis of the above description
The change or variation of multi-form, cannot be exhaustive to all of embodiment here, every technical side for belonging to the present invention
Case it is extended obvious change or change still in protection scope of the present invention row.
Claims (9)
1. a kind of methylphenidate hydrochloride oral solution, it is characterised in that：The oral administration solution prescription composition include methylphenidate hydrochloride,
PH adjusting agent, antioxidant, preservative, stabilizer, correctivess.
2. a kind of methylphenidate hydrochloride oral solution as claimed in claim 1, it is characterised in that：Containing methylphenidate hydrochloride, resist
Oxygen agent (0.01% ~ 0.1%), correctivess（10%~40%）, pH adjusting agent（2%~8%）, stabilizer (10% ~ 30%), preservative（0.01%
~5%）Deng pharmaceutic adjuvant.
3. the methylphenidate hydrochloride oral solution as described in claim 1 and 2, it is characterised in that：The antioxidant includes vitamin
One or more of E, BHA, BHT, disodium edetate.
4. the methylphenidate hydrochloride oral solution as described in claim 1 and 2, it is characterised in that：The taste masking of the oral solution
Agent is selected from sucrose, Sorbitol, saccharin sodium, stevioside, fragrant citrus essence, apple essence, strawberry essence etc. it is therein one or more.
5. the methylphenidate hydrochloride oral solution as described in claim 1 and 2, it is characterised in that：The pH adjusting agent is selected from winestone
Acid, citric acid, the one kind in sodium dihydrogen phosphate or its mixture or pharmaceutically acceptable other buffer solution systems.
6. the methylphenidate hydrochloride oral solution as described in claim 1 and 2, it is characterised in that：The oral solution pH scopes
Between 4.0-6.0.
7. the methylphenidate hydrochloride oral solution as described in claim 1 and 2, it is characterised in that：The anti-corrosion of the oral solution
Agent is selected from one or several in sodium benzoate, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben etc..
8. methylphenidate hydrochloride oral solution as claimed in claim 1 or 2, it is characterised in that the oral solution is stablized
Agent is selected from one or more in glycerol, Propylene Glycol or Macrogol 1450.
9. methylphenidate hydrochloride oral solution as claimed in claim 1 or 2, it is characterised in that its preparation method includes following step
Suddenly：
1）A certain amount of pure water is taken, principal agent, stabilizer, correctivess are added（Sweeting agent）Preservative, antioxidant, slight fever stirring have made
CL, is cooled to room temperature standby；
2）PH value regulator is added into above-mentioned solution into, stirring and dissolving is uniform, filters and add what pure water to population of samples was accumulated
90%；
3）Correctivess are added in above-mentioned solution（Aromatic）, continue to stir, appropriate pure water added after filtration to quantitative.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611003081.6A CN106511264A (en) | 2016-11-15 | 2016-11-15 | Methylphenidate hydrochloride oral solution and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611003081.6A CN106511264A (en) | 2016-11-15 | 2016-11-15 | Methylphenidate hydrochloride oral solution and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN106511264A true CN106511264A (en) | 2017-03-22 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611003081.6A Pending CN106511264A (en) | 2016-11-15 | 2016-11-15 | Methylphenidate hydrochloride oral solution and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107898809A (en) * | 2017-12-15 | 2018-04-13 | 湖南千金协力药业有限公司 | A kind of Zinc calcium gluconate oral solution and preparation method thereof |
| CN108434097A (en) * | 2018-06-22 | 2018-08-24 | 南京济群医药科技股份有限公司 | A kind of hydrochloric triprolidine oral solution of stabilization and preparation method thereof |
| WO2020239052A1 (en) * | 2019-05-30 | 2020-12-03 | 特丰制药有限公司 | Chloral hydrate-containing medicinal kit and uses thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368876A (en) * | 1997-12-15 | 2002-09-11 | 诺芬药品公司 | Compositions and methods of treatment of attention deficit disorder and attention dificit/hyperactivity disorder with methylphenidate |
| US20060257323A1 (en) * | 2005-05-02 | 2006-11-16 | Kulli John C | Preventing insufflation and injection modes of drug abuse |
| CN1867359A (en) * | 2003-10-08 | 2006-11-22 | 马林克罗特公司 | Methylphenidate solution and associated methods of administration and produciton |
| CN101011366A (en) * | 2005-09-26 | 2007-08-08 | 刘凤鸣 | Slow release tablet of methylphenidate |
-
2016
- 2016-11-15 CN CN201611003081.6A patent/CN106511264A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1368876A (en) * | 1997-12-15 | 2002-09-11 | 诺芬药品公司 | Compositions and methods of treatment of attention deficit disorder and attention dificit/hyperactivity disorder with methylphenidate |
| CN1867359A (en) * | 2003-10-08 | 2006-11-22 | 马林克罗特公司 | Methylphenidate solution and associated methods of administration and produciton |
| US20060257323A1 (en) * | 2005-05-02 | 2006-11-16 | Kulli John C | Preventing insufflation and injection modes of drug abuse |
| CN101011366A (en) * | 2005-09-26 | 2007-08-08 | 刘凤鸣 | Slow release tablet of methylphenidate |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107898809A (en) * | 2017-12-15 | 2018-04-13 | 湖南千金协力药业有限公司 | A kind of Zinc calcium gluconate oral solution and preparation method thereof |
| CN108434097A (en) * | 2018-06-22 | 2018-08-24 | 南京济群医药科技股份有限公司 | A kind of hydrochloric triprolidine oral solution of stabilization and preparation method thereof |
| WO2020239052A1 (en) * | 2019-05-30 | 2020-12-03 | 特丰制药有限公司 | Chloral hydrate-containing medicinal kit and uses thereof |
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| PB01 | Publication | ||
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Application publication date: 20170322 |