CN106806341A - A kind of fexofenadine suspension and preparation method thereof - Google Patents
A kind of fexofenadine suspension and preparation method thereof Download PDFInfo
- Publication number
- CN106806341A CN106806341A CN201510905788.5A CN201510905788A CN106806341A CN 106806341 A CN106806341 A CN 106806341A CN 201510905788 A CN201510905788 A CN 201510905788A CN 106806341 A CN106806341 A CN 106806341A
- Authority
- CN
- China
- Prior art keywords
- fexofenadine
- suspension
- preparation
- suspension according
- hydrochloride
- Prior art date
- 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.)
- Pending
Links
Classifications
-
- 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
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/10—Dispersions; Emulsions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides it is a kind of be suitable to children and have dysphagia patient it is oral, have no the fexofenadine suspension formulation of the disagreeable tastes such as bitterness and preparation method.The suspension includes 0.6% fexofenadine, 2% low molecule suspending agent, 0.4% hydrophilic colloid, 0.051% anti-corrosion composition, 20% sucrose, 0.15% chelate stabilizer disodium ethylene diamine tetraacetate, 1.11% buffer system.The bitter taste of fexofenadine hydrochloride is removed in preparation technology by processing methods such as desalination, homogeneous, in suspension 90% fexofenadine grain graininess is less than 25 μm.
Description
Technical field
The present invention relates to pharmaceutical technology field, and in particular to a kind of formula of fexofenadine suspension and its preparation
Method.
Background technology
Fexofenadine is a kind of third generation histamine receptor antagonists, by optionally blocking H1Acceptor reaches
Good antihistamine effect, it is adaptable to the illness such as seasonal allergic rhinitis, chronic idiopathic urticaria.Non- rope
Fei Nading f hardlyes pass through blood-brain barrier, without the effect of medmain, choline and adrenaline, without calm, head
The effect of dizzy, weak and other central nervous systems.Compared to other antihistamines, fexofenadine is not almost led
The serious side effects such as cardiac muscle Q-T extensions are caused, security is high, is particularly suitable for underage child patient and uses.
The fexofenadine formulation of current China's listing has two kinds of tablet and capsule, it is adaptable to adult and 6 years old with
On children.But tablet and capsule volume are larger, easily there are dysphagia feelings when underage child is taken within less than 6 years old
Condition, and the fluid preparation such as suspension will not then have problems that.Therefore from the angle of raising compliance,
Urgently develop non-institute's Fei Nading suspensions that a kind of suitable underage child is taken.
Other children is higher to mouthfeel requirement, should be removed during preparation or masking agentses bitter taste and other not
Good taste, to avoid children from resisting, improves compliance.
Fexofenadine belongs to low-solubility, hypotonicity medicine (BCS IV classes), is made into hydrochloride
The dissolution rate of solid pharmaceutical preparation (tablet, capsule) can to a certain extent be improved, Fexofenadine customization inside and outside native land
The bulk drug (API) that agent is used is fexofenadine hydrochloride, both at home and abroad disclosed pertinent literature and patent
Also using fexofenadine hydrochloride as raw material.Patent disclosed in French Sanofi-Aventis company
CN101316580 describes a kind of preparation method of fexofenadine suspension.The patent is with hydrochloric acid Fei Suofei
That is set to raw material, and principal character includes the fexofenadine amphoteric ion type two containing about 0.03% to about 4.80%
Hydrate forms, the granularity of 90% drug particles is less than 40 microns, and oral administration biaavailability is 40% or so.
Sanofi-Aventis company has corresponding fexofenadine suspension to be sold in the U.S., its tip of the tongue meeting when taking
Feel obvious, undesirable puckery picotement.Another patent disclosed in Sanofi-Aventis company
CN103002874B is coated the method for fexofenadine hydrochloride to shelter bitter taste using hot melt, specific method be
Stearic acid is sprayed on the particulate that fexofenadine hydrochloride is made with hydrophilic polymer under high temperature carried out to it
It is coated.Using auxiliary materials such as PVPs, consumption is 15% or so to wherein hydrophilic polymer；Stearic amount ratio
Example is 50-60%.Another patent CN102958515A discloses one kind and is prepared for the micro- glue of fexofenadine hydrochloride
The method of capsule, needs to use substantial amounts of surfactant and harmful organic solvent and mutually induces in preparation process
Agent, thus its product is restricted in terms of drug safety.Another patent CN102512389A is disclosed
The formula and preparation method of a kind of fexofenadine hydrochloride orally disintegrating tablet, the method system for employing granule coating
Standby disintegrated tablet, coating material is HPMC.Granule coating can to a certain extent alleviate the non-rope of hydrochloric acid
Fei Nading bitterness senses in itself, but coating process is complicated, prepare can use in particulate and coating process compared with
Substantial amounts of auxiliary material.Use in relevant national standard to high polymer adjuvants such as stearic acid, PVPs in pharmaceutical preparation
Amount has strict limitation, lower using limitation in children preparation.Therefore go out from the angle of drug safety
Hair, particulate and coating are not the prefered method for preparing the Fexofenadine customization agent that children are applicable.
The content of the invention
For the problem that above Fexofenadine customization agent is present, the invention provides one kind entirely without bitter taste, mouthfeel
Good, supplementary product consumption is few, be adapted to the formula and preparation method of the fexofenadine suspension that underage child is taken.
It is raw material that the Fexofenadine customization agent for having listed uses fexofenadine hydrochloride.Fexofenadine is customized to salt
Hydrochlorate can in any case increase its water solubility, and the dissolution rate to improving the solid pharmaceutical preparations such as tablet and capsule has one
It is fixed to help.But because suspension formulations solution is buffer solution, its pH scope was being prepared close to neutrality, hydrochloric acid
Be buffered in journey in system and, therefore the hydrochloric acid contained in bulk drug has no that raising fexofenadine is water-soluble, promote
Enter the effect of drug-eluting.
The present invention is had found by studying, original after fexofenadine hydrochloride is the step of by removing hydrochloric acid
Bitter taste is wholly absent, and the flavouring and supplementary product consumption added to cover bitter taste in preparation can be greatly decreased.No
Mouthfeel is only improved, while also improving drug safety.
Studied according to more than, the invention provides a kind of not hydrochloric or chlorion composition, be adapted to children taking
Fexofenadine suspension.Its composition includes 0.6% fexofenadine, 2% low molecule suspending agent suspending agent, 0.5%
Hydrophilic colloid, 0.051% anti-corrosion composition, 20% sucrose, 0.15% chelate stabilizer EDTA, 1.11% buffer system
System.
The granularity of 90% fexofenadine drug particles is less than 25 μm in this suspension；
Low molecule suspending agent is propane diols；
Hydrophilic colloid is combined for xanthans with the compatibility of sodium carboxymethylcellulose；
Buffer system is made up of 0.675% disodium hydrogen phosphate and 0.435% sodium dihydrogen phosphate；
Anti-corrosion composition is made up of 0.034% propylben and 0.017% Buddhist nun pool butyl ester.
This suspension uses two kinds of hydrophilic colloids of xanthans and sodium carboxymethylcellulose.Xanthans has thixotropy,
Suspension is set to be easy to topple over and swallow by what is become after shaking.Sodium carboxymethylcellulose is used as electrically charged support
Skeleton auxiliary material enhancing fexofenadine decentralization in aqueous, remains that the settling ratio of suspension is approached
1。
The moderate viscosity of this suspension, being adapted to underage child and other has the patient of aphetite disorder oral.
The pharmaceutic adjuvant consumption of this suspension is all below generally acknowledged pharmaceutic adjuvant threshold limit values, and preparation
Matter stabilization.
In Vitro Dissolution experiment is the standard method for evaluating oral solid formulation and mixed suspension preparation dissolution rate.It is molten in vitro
Go out experiment in, according to the present invention prepare fexofenadine suspension (not hydrochloric) on dissolution rate with state
Outer fexofenadine hydrochloride suspension on sale is basically identical, and the dissolution rate within 10 minutes has reached 95%
More than.In the pharmacokinetic trial carried out on experimental animal (SD rats), prepared according to the present invention
Fexofenadine suspension (not hydrochloric) salt on sale with foreign countries in peak blood drug level, bioavilability
Sour fexofenadine suspension is basically identical, and blood concentration reaches peak speed 0.5 hour faster than the latter, to a certain degree
Upper reflection is according to the fexofenadine suspension (not hydrochloric) of present invention preparation compared with fexofenadine hydrochloride
Infiltration rate in animal body is faster.This result has broken insoluble drug and has paid the utmost attention to be prepared into salt carry
The Normal practice of oral formulations dissolution rate high.
The invention provides the fexofenadine suspension liquid and preparation method thereof that a kind of process is simple, quality are easily controlled.
It is the method for bulk drug that this method is different from existing Fexofenadine customization agent and uses fexofenadine hydrochloride, first
With the hydrochloric acid in sodium hydroxide solution and contained by fexofenadine hydrochloride between pH value 6-7, by 3-4 times
Washing removes filtration drying after the sodium chloride that neutralization reaction is produced.Not hydrochloric fexofenadine is added to and is contained
Have in the phosphate buffer of disodium ethylene diamine tetraacetate and sodium carboxymethylcellulose, incited somebody to action using high-speed emulsifying homogeneous machine
Drug particles size distribution is down to claimed range.After adding sucrose to stir afterwards, it is slowly injected into and contains uniform point
Scattered xanthans and the propylene glycol solution of preservative.Pure water supplies volume standing and treats that maturation is bottled after stirring.
Pharmaceutical properties and preparation process specifically will sufficiently be shown with reference to following embodiments with data.
Brief description of the drawings
Fig. 1：The microphoto of fexofenadine particle in fexofenadine suspension of the present invention；
Fig. 2：The dissolution determination result of fexofenadine suspension of the present invention；
Fig. 3：Fexofenadine suspension pharmacokinetics liquid phase diagram of the present invention；
Fig. 4：The pharmacokinetic studies result of fexofenadine suspension of the present invention.
Specific implementation case
Embodiment 1:
Weigh in appropriate hydrochloric acid fexofenadine addition pure water, 1mM NaOH are slowly dropped under stirring will be water-soluble
The pH of liquid is adjusted to 6.8 or so.Filter cake is collected after filtering, and 4 times are filtered with after pure water filter cake, then do
It is dry to obtain not hydrochloric Fexofenadine fixed solid.Weigh appropriate disodium ethylene diamine tetraacetate and carboxymethylcellulose calcium
Sodium is dissolved in 80mL phosphate buffers, enters back into fexofenadine obtained in the previous step, is emulsified with high speed equal
Matter machine is processed 20 minutes in 13000r/min, is subsequently adding 20g sucrose into fexofenadine suspension.Another
Appropriate propylben and butyl hydroxybenzoate are dissolved in propane diols in one container, add appropriate xanthans,
And it is dispersed into homogeneous solution with high-speed emulsifying homogeneous machine.Take the 2mL propylene glycol solutions and be added to previous step and obtain
Fexofenadine suspension in, supply pure water to 100mL, stand and be finished product after bottling after maturation.
Per 100mL fexofenadine suspension ingredients：
The granularity of 90% fexofenadine drug particles is less than 25 μm in suspension, sees Fig. 1.
Prepared supensoid agent has good thixotropy, and viscosity is 4528Pas during standing, when rotating speed is 0.03S
When viscosity drop to 294Pas.
(1) In Vitro Dissolution experiment
The fexofenadine suspension for preparing is taken, according to dissolution method (paddle method) with 900mL water as molten
Agent, temperature is 37 degrees Celsius, and rotating speed is 50r/min, is operated in accordance with the law.5,10,15,25 are set respectively,
55min samples 5mL, 20 microlitres of injection liquid phases is directly taken after filtering and is analyzed.Use American market simultaneously
Fexofenadine suspension (the trade name of upper sale：Allegra In Vitro Dissolution comparing) is carried out as control sample,
See Fig. 2.
Fexofenadine suspension In Vitro Dissolution value
| Dissolution rate (%) | 5min | 10min | 15min | 25min | 55min |
| From grinding sample | 0.94 | 0.98 | 0.98 | 0.99 | 1 |
| Original grinds sample | 0.91 | 0.97 | 0.97 | 0.98 | 1 |
(2) pharmacokinetic studies
After each six SD rats of male and female are taken by the dosage gavage of 3mg/kg, respectively at 0.25,0.5,1,1.5,
2nd, strength arterial blood 0.3mL is taken within 2.5,3,4,6 hours, anticoagulant heparin is made plasma sample.Take blood plasma sample
100 microlitres of product, are redissolved after taking the drying of supernatant nitrogen after addition inner mark solution acetonitrile vortex, centrifugation with methyl alcohol
To analysis sample, content analysis are carried out with high performance liquid chromatograph, see Fig. 3.City of the U.S. is analyzed in the same way
Fexofenadine suspension (the trade name sold on field：Allegra characteristics of pharmacokinetics), and be compared,
See Fig. 4.
Fexofenadine suspension pharmacokinetic parameter
| Pharmacokinetics | |||
| From grinding sample | 1.5 | 1.15 | 5.35 |
| Original grinds sample | 2 | 1.16 | 4.97 |
Claims (7)
1. a kind of fexofenadine suspension, it is characterised in that：
1) particle diameter distribution：The granularity of 90% drug particles is less than 25 μm；
2) not hydrochloric or chlorion composition；
3) it is constituted includes 0.6% fexofenadine, 2% low molecule suspending agent, 0.4% hydrophilic colloid, and 0.051% prevents
Rotten composition, 20% sucrose, 0.15% chelate stabilizer disodium ethylene diamine tetraacetate, 1.11% buffer system.
2. fexofenadine suspension according to claim 1, it is characterised in that the low molecule suspending agent is third
Glycol.
3. fexofenadine suspension according to claim 1, it is characterised in that the hydrophilic colloid is 2.5%
Xanthans and 1.5% sodium carboxymethylcellulose.
4. fexofenadine suspension according to claim 1, it is characterised in that the anti-corrosion composition is by 0.034%
Propylben and 0.017% butyl hydroxybenzoate are constituted.
5. fexofenadine suspension according to claim 1, it is characterised in that buffer system is by 0.675% phosphoric acid
Disodium hydrogen and 0.435% sodium dihydrogen phosphate are constituted.
6. fexofenadine suspension according to claim 1, it is characterised in that the viscosity when suspension stands
No more than 4.5MPas, after being stirred as 0.3r/s with rotating speed, viscosity is not more than 0.3MPas.
7. a kind of method for preparing fexofenadine suspension as claimed in claim 1, its step is：
1) hydrochloric acid contained by fexofenadine hydrochloride is removed, method is to titrate fexofenadine hydrochloride with sodium hydroxide solution
The suspension in water is scheduled on between pH value 6-7；
2) above-mentioned suspension is filtered, and washes filter cake with water and removed the sodium chloride of generation completely 3-4 times, filtration cakes torrefaction
It is standby afterwards；
3) propylben and butyl hydroxybenzoate are dissolved in propane diols, add xanthans, and emulsified with high speed equal
Matter machine is dispersed into homogeneous solution A；
4) phosphate buffer is configured, adds sodium carboxymethylcellulose, disodium ethylene diamine tetraacetate to stir to dissolving, plus
Enter the fexofenadine drying solid of a certain amount of above-mentioned removing hydrochloric acid, using high-speed emulsifying homogeneous machine by medicine
Grain size distribution is down to claimed range, and solution B is made after adding sucrose dissolving；
5) A is slowly added into B and is stirred, volume is supplied with pure water, bottling is final product after standing maturation
Product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510905788.5A CN106806341A (en) | 2015-12-09 | 2015-12-09 | A kind of fexofenadine suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510905788.5A CN106806341A (en) | 2015-12-09 | 2015-12-09 | A kind of fexofenadine suspension and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106806341A true CN106806341A (en) | 2017-06-09 |
Family
ID=59105977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510905788.5A Pending CN106806341A (en) | 2015-12-09 | 2015-12-09 | A kind of fexofenadine suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106806341A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115715759A (en) * | 2022-11-03 | 2023-02-28 | 京海盛达(北京)科技有限公司 | Anti-histamine suspension and preparation method thereof |
-
2015
- 2015-12-09 CN CN201510905788.5A patent/CN106806341A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115715759A (en) * | 2022-11-03 | 2023-02-28 | 京海盛达(北京)科技有限公司 | Anti-histamine suspension and preparation method thereof |
| CN115715759B (en) * | 2022-11-03 | 2024-01-12 | 京海盛达(北京)科技有限公司 | Antihistamine suspension and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3181122B1 (en) | Dasatinib pharmaceutical composition | |
| CN101123951A (en) | Pharmaceutical dosage forms comprising a low-solubility drug and a polymer | |
| CN108498456A (en) | A kind of Aripiprazole sustained-release micro-spheres and preparation method thereof | |
| CN104116741B (en) | Vilazodone Hydrochloride composition and preparation method thereof | |
| CN107049985A (en) | A kind of long-acting slow-release preparation of antiparkinsonism drug and preparation method thereof | |
| CN102614492B (en) | Liquid pharmaceutical composition containing echinocandin antifungal agent micafungin | |
| CN105125485A (en) | Preparation method of injecting drug improving stability of puerarin drug injection preparation | |
| CN106806341A (en) | A kind of fexofenadine suspension and preparation method thereof | |
| CN105193841A (en) | Compound reserpine medicine composition for treating hypertension and preparation method of compound reserpine medicine composition | |
| CN103735513B (en) | A kind of 20 (s)-protopanoxadiol nanoparticle and preparation method thereof | |
| CN105213425A (en) | One treats hypertensive compound recipe reserpine oral cavity disintegration tablet and preparation method thereof | |
| CN111184693B (en) | RAF kinase inhibitor preparation and preparation method thereof | |
| EP2000152A9 (en) | Solid preparation having improved solubility | |
| CN106860404A (en) | A kind of sildenafil citrate taste masking resin complexes and its application | |
| CN106880611A (en) | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing | |
| NZ564927A (en) | Pharmaceutical formulation of the tubulin inhibitor Indibulin for oral administration with improved pharmacokinetic properties, and process for the manufacture thereof | |
| Patel et al. | Stomach-specific drug delivery of famotidine using floating alginate beads | |
| CN105902564B (en) | A kind of pharmaceutical composition and preparation method for treating hypertension | |
| CN105708808A (en) | Epinastine hydrochloride granule, and preparation method thereof | |
| CN105030732A (en) | Microspheres obtained through liquid crystal nanoparticles packed by chitosan and preparation method thereof | |
| CN106913544B (en) | A kind of Gefitinib tablet of Fast Stripping and preparation method thereof | |
| CN101006974A (en) | Ophthalmic gel and its preparation method | |
| CN105636587B (en) | Pharmaceutical preparation containing amino-pyrazol-derivatives | |
| CN107184555A (en) | A kind of Procaterol Hydrochloride granule and preparation method thereof | |
| CN106109458A (en) | Puerarin for Injection nanocrystal and preparation technology thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170609 |