CN104644574B - A kind of sildenafil citrate taste masking preparation - Google Patents
A kind of sildenafil citrate taste masking preparation Download PDFInfo
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Abstract
The invention discloses a kind of sildenafil citrate taste masking preparation and preparation method thereof, the sildenafil citrate taste masking preparation at least contains the sildenafil citrate based on total weight of tablet 15% 30%, 30% 65% hydroxypropyl cellulose, 15% 20% Compritol 888 ATOs；The preparation method includes the sildenafil citrate of recipe quantity and hydroxypropyl cellulose being mixed and made into melting dispersion, then cuts into particle, and the particle with other auxiliary materials with after Compritol 888 ATO co-ground, being well mixed, being pressed into and be available for oral tablet.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of sildenafil citrate taste masking preparation and preparation method thereof.
Background technology
Sildenafil citrate is treatment erectile dysfunction（ED）Oral medicine, be a kind of to cyclic guanosine monophosphate（cGMP）
5 special type phosphodiesterases（PDE5）Selective depressant.Mechanism of action：The physiological mechanism of telotism is related to sexual stimulus mistake
Corpora cavernosa penis intracellular nitric oxide in journey（NO）Release.NO activation guanylate cyclases cause cyclic guanosine monophosphate（cGMP）Level
Increase, make smooth muscle relaxation in cavernous body, blood engorgement.Silaenafil is that high selectivity PDE5 (PDE5) suppresses
Agent, PDE5 altimeters in corpora cavernosa penis reach, and in other tissues（Including blood platelet, blood vessel and visceral smooth muscle, bone
Flesh）, expression is lowly.Silaenafil strengthens nitric oxide (NO)-cGMP approach by selective depression PDE5, raises cGMP water
Put down and cause corpus cavernosum smooth muscle to relax, patients with erectile dysfunction is produced natural erectile response to sexual stimulus.Suddenly
React typically strengthens with the increase of silaenafil dosage and plasma concentration.In addition, silaenafil is also used for treating pulmonary artery
High pressure, it is regardless of sex.
Sildenafil citrate is to be white to off-white color crystalline powder, and taste is extremely bitter, is slightly soluble in water, methanol, almost insoluble
In acetonitrile, ethanol or ether.It is tablet that it, which lists formulation,.For having patient, gerontal patient or the water intaking of aphetite disorder or difficulty
The patient of inconvenience, the clinical practice of this tablet receives limitation partially or completely.In addition, Sildenafil citrate tablets have compared with
Big piece shape and piece weight.Understand after measured, commercially available Sildenafil citrate tablets（Specification 0.1g, Pfizer has
Limit company）For the tablet of rhombus biconvex, it is grown and wide respectively 14.5mm and 11.0mm, has more aggravated the difficulty of patient swallow,
It has impact on its clinical adaptability.
Therefore, in order to improve above mentioned problem, it is necessary to develop and develop the novel form for facilitating clinical practice, such as Orally disintegrating
Piece.Oral disnitegration tablet is not required to drink water or only needs minimal amount water i.e. disintegratable release medicine, without chewing, and saliva is met in the oral cavity and is
Disintegration, release, to there is the patient of aphetite disorder or difficulty, gerontal patient or the inconvenient patient medication of water intaking to provide very big side
Just.
Similar preparation has seen report.Patent 201310011700.6 disclose it is a kind of containing sildenafil citrate and
The Pharmaceutical composition of PD-1 type pregelatinized starch, it is characterised in that the Pharmaceutical composition is can be at 15 seconds to 30 seconds in 37 DEG C of water
Interior complete disintegration, and can be by 600~710 μm of screen cloth.Patent 200810166942.1 discloses a kind of containing diluent
Oral disintegrative tablet of sildenafil citrate.Patent 200810097300.0,200610009940.2 individually discloses citric acid west
That non-sublingual lozenge of ground.
But, found in research according to the prescription of published oral disintegrative tablet of sildenafil citrate or sublingual lozenge and
The preparation that preparation method is made, the disagreeable taste of main sildenafil citrate can not be covered completely, although being added in prescription
Miscellaneous sweetener and flavouring, but the more or less bitter taste that embodies main ingredient in oral, largely
The mouthfeel of said preparation is have impact on, clinical adaptability and tolerance is limited.Because, sildenafil citrate is with extremely hardship
Bitter taste, and specification is larger（The pieces of 140.5mg/ containing sildenafil citrate）, pass through the taste masking sides such as conventional auxiliary material dilution, flavouring
Method, is difficult to realize complete, good taste masking.
The content of the invention
It is an object of the present invention to provide a kind of sildenafil citrate taste masking preparation, at least containing based on tablet total weight
Measure 15%-30% sildenafil citrate, the hydroxypropyl cellulose as odor mask based on total weight of tablet 30%-65%
（HPC）, based on total weight of tablet 15%-20% Compritol 888 ATOs.
Preferably, sildenafil citrate accounts for the 17.5%~25.0% of prescription total amount, more preferably 22.5%；HPC accounts for prescription
The 40.0%~55.0% of composition, more preferably 48.0%, HPC may be selected from trade name KlucelTMCommercially available prod, preferably be selected from
KlucelTMELF、KlucelTMEF、KlucelTMLF and KlucelTMOne or more in JF；Compritol 888 ATO accounts for prescription group
Into 17.5%.
Sildenafil citrate taste masking preparation of the present invention, in addition to pharmaceutically acceptable adjunct ingredient, including
The disintegrant of filler, 0.5%-4.0% based on total weight of tablet 3%-21%, 0.2%-1.0% flavouring, 0.5%-1.5%
Lubricant, wherein the filler is the one or more in xylitol, sorbierite and mannitol, the disintegrant is choosing
One or more in self-crosslinking sodium carboxymethylcellulose, sodium carboxymethyl starch and PVPP, the flavouring be selected from
One kind or many in one or both of Mint Essence and lemon extract, the magnesium stearate lubricant, sodium stearyl fumarate
Kind.
In above-mentioned auxiliary material composition, filler preferably 8.0%, disintegrant preferably 2.5%, flavouring preferably 0.5%, lubricant is excellent
Select 1.0%.
Sildenafil citrate taste masking preparation of the present invention, is prepared from by following methods：
（1）The sildenafil citrate of recipe quantity is mixed with hydroxypropyl cellulose, melting dispersion is made；
（2）Melting dispersion be cut be broken into diameter about 1mm particle after mixed with Compritol 888 ATO；
（3）Milled mixtures, obtain abrasive grains
（4）Will grinding mixed with pharmaceutically acceptable adjunct ingredient, tabletting.
Further, step（1）The mixture of middle sildenafil citrate and hydroxypropyl cellulose is with heater
Double screw extruder in handled, throughput is 1kg/h, during temperature gradually risen by 20 DEG C to 170 DEG C
~200 DEG C, finally extruded at diameter 2mm discharging gate；Step（3）Middle milled mixtures obtain abrasive grains after 20 mesh sieves.
Further, above-mentioned preparation method is：The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in
In double screw extruder, throughput is 1kg/h, during temperature gradually risen by 20 DEG C to 180 DEG C, finally in diameter
Extruded at 2mm discharging gate, the melting dispersion tow of gained is cut the particle for being broken into diameter about 1mm, by particle and mountain
Yu acid glycerides are mixed, and this mixture is placed in impact grinder and ground, by 20 mesh sieves, abrasive grains are obtained；Above-mentioned grinding
The filler of particle and recipe quantity, disintegrant, flavouring, mix lubricant are uniform, re-compacted into being available for oral tablet.
In the present invention, it is crucial, melting dispersion and behenyl acid glycerol that melting dispersion is co-mulled and made into Compritol 888 ATO
Ester co-ground makes Compritol 888 ATO be well-dispersed in the surface of melting dispersion granule, enhances taste masking effect, and HPC is not
Only it is the scattered medium of melting, also functions to taste masking effect, the tablet being made based on this has completely eliminated said preparation in mouth
The bitter taste being likely encountered when taking and bad mouthfeel.
Brief description of the drawings
Fig. 1 is stripping curve contrast of the sildenafil citrate melting dispersion taste masking preparation in pure water.
Embodiment
The technical scheme that the present invention is provided can be more fully understood by with the following Examples.These embodiments are intended to this
The pharmaceutical composition and dosage form that invention is provided is illustrated, but is not limited in any way.
Raw material used in following examples and equipment, except special instruction, are common commercially available.
Twin-screw melt extruder model and manufacturer：ME-D16, Shenzhen Xinyi spy Science and Technology Ltd.
【Embodiment 1】Sildenafil citrate melting dispersion-be co-mulled and made into thing taste masking preparation and preparation method thereof
Prescription：
* equivalent to silaenafil free alkali 100mg, with " preparation specification：0.1g " implications are identical.Similarly hereinafter.
Preparation method：
The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in double screw extruder, and throughput is
1kg/h, during temperature gradually risen by 20 DEG C to 180 DEG C, finally at diameter 2mm discharging gate extrude, gained
Melting dispersion tow be cut and be broken into diameter about 1mm particle.Above-mentioned particle is mixed with Compritol 888 ATO, and this is mixed
Compound is placed in impact grinder and ground, then by 20 mesh sieves, obtains abrasive grains；The xylose of above-mentioned abrasive grains and recipe quantity
Alcohol, Ac-Di-Sol, lemon extract are placed in V-arrangement mixer and mix 10min, add magnesium stearate mixing
3min, intermediate is through after the assay was approved, being pressed into diameter 12mm circular tablet.With aluminium foil and polyvinyl chloride/poly- inclined two chloroethene
Alkene composite hard sheet（PVC/PVDC）Composite packaging is carried out, is got product through mounted box after the assay was approved.
【Embodiment 2】Sildenafil citrate melting dispersion-be co-mulled and made into thing taste masking preparation and preparation method thereof
Prescription：
| Composition | Classification | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 35.1 | 15.0 |
| HPC(KlucelTMELF) | Diluent/odor mask | 140.6 | 60.0 |
| Compritol 888 ATO | Odor mask | 35.1 | 15.0 |
| Mannitol | Filler/odor mask | 18.0 | 7.7 |
| Sodium carboxymethyl starch | Disintegrant | 2.4 | 1.0 |
| Mint Essence | Flavouring | 0.7 | 0.3 |
| Magnesium stearate | Lubricant | 2.4 | 1.0 |
| It is total | 234.3mg | 100.0 |
Preparation method：
The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in double screw extruder, and throughput is
1kg/h, during temperature gradually risen by 20 DEG C to 170 DEG C, finally at diameter 2mm discharging gate extrude, gained
Melting dispersion tow be cut and be broken into diameter about 1mm particle.Above-mentioned particle is mixed with Compritol 888 ATO, and this is mixed
Compound is placed in impact grinder and ground, then by 20 mesh sieves, obtains abrasive grains；The sweet dew of above-mentioned abrasive grains and recipe quantity
Alcohol, sodium carboxymethyl starch, Mint Essence are placed in V-arrangement mixer and mix 10min, add magnesium stearate mixing 3min, middle
Body is through after the assay was approved, being pressed into diameter 9mm circular tablet.With aluminium foil and polyvinyl chloride/polyvinylidene chloride composite hard sheet
（PVC/PVDC）Composite packaging is carried out, is got product through mounted box after the assay was approved.
【Embodiment 3】Sildenafil citrate melting dispersion-be co-mulled and made into thing taste masking preparation and preparation method thereof
Prescription：
| Composition | Classification | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 140.5 | 30.0 |
| HPC(KlucelTMJF) | Diluent/odor mask | 140.5 | 30.0 |
| Compritol 888 ATO | Odor mask | 93.7 | 20.0 |
| Mannitol | Filler/odor mask | 35.1 | 7.5 |
| Sorbierite | Filler/odor mask | 28.1 | 6.0 |
| PVPP | Disintegrant | 18.7 | 4.0 |
| Lemon extract | Flavouring | 4.7 | 1.0 |
| Sodium stearyl fumarate | Lubricant | 7.0 | 1.5 |
| It is total | 468.3mg | 100.0 |
Preparation method：
The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in double screw extruder, and throughput is
1kg/h, during temperature gradually risen by 20 DEG C to 200 DEG C, finally at diameter 2mm discharging gate extrude, gained
Melting dispersion tow be cut and be broken into diameter about 1mm particle.Above-mentioned particle is mixed with Compritol 888 ATO, and this is mixed
Compound is placed in impact grinder and ground, then by 20 mesh sieves, obtains abrasive grains；The sweet dew of above-mentioned abrasive grains and recipe quantity
Alcohol, sorbierite, PVPP, lemon extract are placed in V-arrangement mixer and mix 10min, add sodium stearyl fumarate mixing
3min, intermediate is through after the assay was approved, being pressed into diameter 11mm circular tablet.With aluminium foil and polyvinyl chloride/poly- inclined two chloroethene
Alkene composite hard sheet（PVC/PVDC）Composite packaging is carried out, is got product through mounted box after the assay was approved.
【Embodiment 4】Sildenafil citrate melting dispersion-be co-mulled and made into thing taste masking preparation and preparation method thereof
Prescription：
| Composition | Classification | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 70.3 | 17.5 |
| HPC(KlucelTMLF) | Diluent/odor mask | 168.6 | 42.0 |
| Compritol 888 ATO | Odor mask | 60.2 | 15.0 |
| Mannitol | Filler/odor mask | 76.3 | 19.0 |
| Ac-Di-Sol | Disintegrant | 8.0 | 2.0 |
| Sodium carboxymethyl starch | Disintegrant | 8.0 | 2.0 |
| Mint Essence | Flavouring | 4.0 | 1.0 |
| Magnesium stearate | Lubricant | 6.0 | 1.5 |
| It is total | 401.4mg | 100.0 |
Preparation method：
The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in double screw extruder, and throughput is
1kg/h, during temperature gradually risen by 20 DEG C to 190 DEG C, finally at diameter 2mm discharging gate extrude, gained
Melting dispersion tow be cut and be broken into diameter about 1mm particle.Above-mentioned particle is mixed with Compritol 888 ATO, and this is mixed
Compound is placed in impact grinder and ground, then by 20 mesh sieves, obtains abrasive grains；The sweet dew of above-mentioned abrasive grains and recipe quantity
Alcohol, Ac-Di-Sol, sodium carboxymethyl starch, Mint Essence are placed in V-arrangement mixer and mix 10min, add hard
Fatty acid magnesium mixing 3min, intermediate is through after the assay was approved, being pressed into diameter 11mm circular tablet.With aluminium foil and polyvinyl chloride/
Polyvinylidene chloride composite hard sheet（PVC/PVDC）Composite packaging is carried out, is got product through mounted box after the assay was approved.
【Embodiment 5】The mouthfeel contrast of sildenafil citrate melting dispersion-the be co-mulled and made into thing taste masking preparation of optimization is commented
Valency
By test preparation：Taste masking preparation described in embodiment 1
Comparative formulation 1：Commercially available Sildenafil citrate tablets（Specification 0.1g, pfizer inc）
Comparative formulation 2：Use citric acid west prepared by Chinese Patent Application No. technology described in NO.201310011700.6
That non-taste masking preparation of ground, specific formulation and technology is as follows：
Prescription：
| Composition | Classification | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 140.5 | 22.5 |
| Partially pregelatinized starch | Filler | 50.0 | 8.0 |
| PVP k30 | Adhesive | 10.0 | 1.6 |
| Lactose | Filler | 260.0 | 41.6 |
| Mannitol | Filler/odor mask | 123.8 | 19.8 |
| PVPP | Disintegrant | 31.3 | 5.0 |
| Lemon extract | Flavouring | 3.1 | 0.5 |
| Magnesium stearate | Lubricant | 6.3 | 1.0 |
| It is total | 625.0mg | — |
Preparation method：
Sildenafil citrate and partially pregelatinized starch are well mixed, are placed in fluidised bed granulator, the machine that blows in, plus
Heat, makes material be in fluidized state, and the PVP k30 aqueous solution for spraying into 5% is pelletized, and appropriate water is filled spray if necessary to be formed
Suitable particle, keeps 45 ± 5 DEG C of hot blast temperature, makes particle drying to moisture below 2.5%.Above-mentioned particle is passed through into 20 mesh sieves
Net whole grain.Above-mentioned particle is well mixed with lactose, mannitol, PVPP, lemon extract and magnesium stearate, tabletting, i.e.,
.
Comparative formulation 3：Use citric acid west prepared by Chinese Patent Application No. technology described in NO.200810097300.0
That non-taste masking preparation of ground, specific formulation and technology is as follows：
Prescription：
| Composition | Classification | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 140.5 | 22.5 |
| Mannitol | Filler/odor mask | 120.0 | 19.2 |
| HPMC | Adhesive | 12.5 | 2.0 |
| Microcrystalline cellulose | Filler | 127.0 | 20.3 |
| Lactose | Filler | 200.0 | 32.0 |
| Ac-Di-Sol | Disintegrant | 15.6 | 2.5 |
| Lemon extract | Flavouring | 3.1 | 0.5 |
| Magnesium stearate | Lubricant | 6.3 | 1.0 |
| It is total | 625.0mg | — |
Preparation method：
Sildenafil citrate and mannitol are well mixed, is placed in impact grinder and is fully ground, 80 mesh sieves are crossed, it is standby
With；HPMC is dissolved in the solution that water is made into 5%；Above-mentioned sildenafil citrate and mannitol mixture are placed in wet-mixing granulation
In machine, open stirring and shear, add the HPMC aqueous solution of recipe quantity, add appropriate water and supply amount of liquid, reach material
To suitable state, and wet granular is made.Wet granular is placed in fluidized bed dryer and dried, drying temperature is 45 ± 5 DEG C, is done
It is dry to moisture below 2.5%.Above-mentioned particle is passed through into 16 eye mesh screen whole grains.By the microcrystalline cellulose of above-mentioned particle and recipe quantity, breast
Sugar, Ac-Di-Sol, lemon extract and magnesium stearate are well mixed, and tabletting is produced.
Comparative formulation 4：
A kind of sildenafil citrate melts dispersion taste masking preparation（Nothing is co-mulled and made into）
The present embodiment as a comparison preparation come show the present invention Compritol 888 ATO co-rotational procedure in taste masking preparation
Key effect.
Prescription：
| Composition | Effect | Content (mg/ pieces) | Percentage composition (%) |
| Sildenafil citrate | Main ingredient | 140.5 | 22.5 |
| HPC(KlucelTMEF) | Diluent/odor mask | 375.0 | 60.0 |
| Xylitol | Filler/odor mask | 84.5 | 13.5 |
| Ac-Di-Sol | Disintegrant | 15.6 | 2.5 |
| Lemon extract | Flavouring | 3.1 | 0.5 |
| Magnesium stearate | Lubricant | 6.3 | 1.0 |
| It is total | 625.0mg | — |
Preparation method：
The sildenafil citrate for weighing recipe quantity is well mixed with HPC, is placed in double screw extruder, and throughput is
1kg/h, during temperature gradually risen by 20 DEG C to 180 DEG C, finally at diameter 2mm discharging gate extrude, gained
Melting dispersion tow be cut and be broken into diameter about 1mm particle, be then placed in grinding in impact grinder, then pass through
20 mesh sieves, must melt dispersion fine grained；Xylitol, the cross-linked carboxymethyl fiber of above-mentioned melting dispersion fine grained and recipe quantity
Plain sodium, lemon extract are placed in V-arrangement mixer and mix 10min, add magnesium stearate mixing 3min, and intermediate is qualified through examining
Afterwards, it is pressed into diameter 12mm circular tablet.
It is above-mentioned to be evaluated its mouthfeel respectively by test preparation and 4 kinds of Comparative formulations.15 health volunteers taste respectively at random by
Test preparation and 3 kinds of Comparative formulations, according to mouth feel score, standards of grading are：1=taste is extremely bitter, 2=more bitter, 3=slight bitter, 4=atomic hardship, 5
=without bitter taste.Score is higher, and its mouthfeel is better.Evaluation result such as following table.
As a result it is visible, the sildenafil citrate melting dispersion-be co-mulled and made into thing taste masking preparation for the optimization that embodiment 1 is provided
It is good in taste, almost without bitter taste, hence it is evident that better than 4 kinds Comparative formulations.In particular, taste masking preparation of the present invention is compared with Comparative formulation 4,
Show the necessity of Compritol 888 ATO co-rotational procedure.
【Embodiment 6】Show that the taste masking of invention formulation is acted on by the stripping curve contrast of medicine.
By test preparation：The taste masking preparation of embodiment 1,2,3,4
Comparative formulation：Commercially available Sildenafil citrate tablets（Specification 0.1g, pfizer inc）、
" the Comparative formulation 4 in embodiment 5 ".
Assay method：Using《Chinese Pharmacopoeia》Two annex X C the first methods of dissolution method of version in 2010（Basket method）, it is molten
Go out medium for pure water 900ml；Rotating speed：100 revs/min；Assay method：Ultraviolet spectrophotometry, Detection wavelength 290nm.
Stripping curve measurement result is as shown in following table and accompanying drawing 1.
Stripping curve contrast of the table sildenafil citrate taste masking preparation in pure water（Dissolution rate, %）
It can be seen that, before releasing the phase, the taste masking preparation of embodiment 1,2,3,4, which discharges, is substantially less than Comparative formulation
And less than the Comparative formulation 4 without Compritol 888 ATO co-rotational procedure, show that tested taste masking preparation is disintegrated and it firm
In a period of time afterwards, medicine will not quickly release and cause to produce bitter taste.And after 30 minutes, tested taste masking preparation is molten
Out-degree reaches more than 80%, meets preparation Dissolution Standards.
Claims (10)
1. a kind of sildenafil citrate preparation, it is characterised in that at least containing the citron based on total weight of tablet 15%-30%
Sour silaenafil, 30%-65% hydroxypropyl cellulose, 15%-20% Compritol 888 ATOs；
The sildenafil citrate preparation is prepared from by following methods：
(1) sildenafil citrate of recipe quantity is mixed with hydroxypropyl cellulose, melting dispersion is made；
(2) melting dispersion is cut to be broken into after particle mixes with Compritol 888 ATO；
(3) milled mixtures, obtain abrasive grains
(4) abrasive grains are mixed with pharmaceutically acceptable adjunct ingredient, tabletting.
2. sildenafil citrate preparation as claimed in claim 1, it is characterised in that at least containing based on total weight of tablet
17.5%-25% sildenafil citrate, 42%-55% hydroxypropyl cellulose, 17.5% Compritol 888 ATO.
3. sildenafil citrate preparation as claimed in claim 2, it is characterised in that at least containing based on total weight of tablet
22.5% sildenafil citrate, 48% hydroxypropyl cellulose.
4. sildenafil citrate preparation as claimed in claim 1, it is characterised in that the preparation also includes pharmaceutically connecing
The adjunct ingredient received, includes the filler based on total weight of tablet 3%-21%, 0.5%-4.0% disintegrant, 0.2%-
1.0% flavouring, 0.5%-1.5% lubricant.
5. sildenafil citrate preparation as claimed in claim 2, it is characterised in that the preparation also includes pharmaceutically connecing
The adjunct ingredient received, including the filler based on total weight of tablet 5%-12%, 2.5% disintegrant, 0.5% flavouring,
1% lubricant.
6. the sildenafil citrate preparation as described in claim 4 or 5, it is characterised in that the filler is selected from xylose
One or more in alcohol, sorbierite and mannitol, the disintegrant is selected from Ac-Di-Sol, CMS
One or more in sodium and PVPP, the flavouring is one kind or two in Mint Essence and lemon extract
Kind, the magnesium stearate lubricant, the one or more of sodium stearyl fumarate.
7. sildenafil citrate preparation as claimed in claim 1, it is characterised in that：Citric acid west ground in the step (1)
That non-mixture with hydroxypropyl cellulose is handled in the double screw extruder with heater, and throughput is 1kg/
H, during temperature gradually risen by 20 DEG C to 170 DEG C~200 DEG C, finally at diameter 2mm discharging gate extrude；Step
Suddenly milled mixtures obtain abrasive grains after 20 mesh sieves in (3).
8. a kind of method for preparing sildenafil citrate preparation, it is characterised in that comprise the following steps：
(1) sildenafil citrate of recipe quantity is mixed with hydroxypropyl cellulose, melting dispersion is made；
(2) melting dispersion is cut to be broken into after particle mixes with Compritol 888 ATO；
(3) milled mixtures, obtain abrasive grains
(4) abrasive grains are mixed with pharmaceutically acceptable adjunct ingredient, tabletting.
9. method as claimed in claim 8, it is characterised in that：It is by based on total weight of tablet 15%-30% in step (1)
Sildenafil citrate is mixed with the hydroxypropyl cellulose based on total weight of tablet 30%-65%, and melting dispersion is made；Step
(2) be will melting dispersion cutting and crushing into being mixed with 15.0%~20.0% Compritol 888 ATO after diameter 1mm particle.
10. sildenafil citrate preparation as claimed in claim 4, it is characterised in that include the component of following restructuring proportioning：
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| FR3027802B1 (en) * | 2014-10-31 | 2018-03-02 | Ethypharm | DOUBLE MASKING TASTE ACTIVE PRINCIPLE GRANULES, PROCESS FOR THEIR PREPARATION AND ORODISPERSIBLE TABLETS CONTAINING SAME |
| CN106310218B (en) * | 2015-11-27 | 2019-12-13 | 深圳奥萨制药有限公司 | tablet composition containing enalapril and folic acid and preparation method thereof |
| CN111388433B (en) * | 2020-03-27 | 2021-11-23 | 广州白云山医药集团股份有限公司白云山制药总厂 | Sildenafil citrate oral preparation and preparation method thereof |
| CN112206213A (en) * | 2020-10-26 | 2021-01-12 | 广州汇元医药科技有限公司 | Sildenafil citrate composition and preparation method thereof |
| CN113712926A (en) * | 2021-08-31 | 2021-11-30 | 南京恒正药物研究院有限公司 | Sildenafil orally disintegrating tablet |
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| Title |
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| 矫味和掩味技术在口服新剂型中的应用;陶涛;《上海医药》;20111231;第32卷(第5期);全文 * |
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