CN110507626A - A kind of preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition - Google Patents
A kind of preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition Download PDFInfo
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- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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Abstract
Present disclose provides a kind of preparation methods of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition; the water content of total pharmaceutic adjuvant is improved into 5.5~7.0wt.%; dry granulation is carried out after Vardenafil hydrochloric acid trihydrate and Nei Jia pharmaceutic adjuvant are mixed; the particle that dry granulation is obtained and additional pharmaceutic adjuvant mixing, tabletting, coating obtain Vardenafil hydrochloric acid piece；Wherein total pharmaceutic adjuvant includes interior plus pharmaceutic adjuvant and additional pharmaceutic adjuvant.The preparation method of the disclosure improves the stability of Vardenafil hydrochloric acid trihydrate pharmaceutical composition under the premise of not influencing preparation dissolution.
Description
Technical field
This disclosure relates to which a kind of preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition, belongs to drug
Preparation technique field.
Background technique
Here statement only provides background information related with the disclosure, without necessarily constituting the prior art.
Vardenafil hydrochloric acid trihydrate is a kind of highly selective di-phosphate ester of Bayer Bitterfeld GmbH drugmaker exploitation listing
- 5 inhibitor of enzyme (PDE-5), the main activation plays therapeutic effect for inhibiting PDE-5 enzyme by specificity, for treating male's yin
Stem erectile dysfunction is the most rapid drug that works so far.The medicine compared with similar products, have it is rapid-action, lasting medicine,
Tolerance is good, Small side effects, the features such as safety is good, and convenient to take, is not influenced by food and alcohol.Take Vardenafil
Clinical report shows that 15 minutes 35% people work afterwards, and for 30 minutes to 1 hour effective percentage up to 81%, half-life period is equal to Xi Dina
Non-, Vardenafil is to 5 times that the rejection ability of PDE-5 is silaenafil.
Vardenafil hydrochloric acid piece (thin membrane coated tablet) was listed in reference in 2010 in U.S. FDA approval listing in 2003
Preparation (RLD), at present in the country's listing of more than 60, the whole world.In 2004, CFDA approval listing Vardenafil hydrochloric acid piece (was advised
Lattice: 5mg, 10mg and 20mg), trade name: Ai Lida, composition are Vardenafil hydrochloric acid trihydrate, microcrystalline cellulose, friendship
Joining povidone, colloidal silicon dioxide, magnesium stearate and coating agent, (ingredient: hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide are yellow
Color iron oxide and red iron oxide).
The Chinese patent CN 1681481A of Bayer Bitterfeld GmbH drugmaker application, publication date: on October 12nd, 2005, open
Drug comprising Vardenafil hydrochloric acid trihydrate, claimed be the preparation side of Vardenafil hydrochloric acid trihydrate
Method and coated tablet comprising Vardenafil hydrochloric acid trihydrate.The patent is Vardenafil hydrochloric acid piece patent, discloses packet
The composition and content of garment piece agent: Vardenafil hydrochloric acid trihydrate accounts for the 0.1~70% of weight, disintegrating agent account for weight 0.1~
10%, lubricant accounts for the 0.1~2% of weight, and optionally, also includes glidant and partially filled agent.Since tablet was coated
Cheng Zhong, trihydrate can be partially or completely dehydrated, active constituent with a variety of polymorphics and the non-uniform presence of pseudopolymorphic forms,
The patent introduces wet air by preparation coating process, and piece is got wet, and the hydrochloric acid for obtaining uniform reproducible form is cut down
That non-trihydrate of ground.But the disclosed invention people is the study found that due to contacting wet air in coating process, it is wet
Spend too big, moisture drying not in time, is also easy to produce viscous pot, intermediate plate, numb piece, phenomena such as coating weight gain is inhomogenous.
Summary of the invention
In order to solve the deficiencies in the prior art, purpose of this disclosure is to provide a kind of stable hydrations of Vardenafil hydrochloric acid three
The preparation method of medicine composition improves the stability of Vardenafil hydrochloric acid trihydrate pharmaceutical composition, solves tablet packet
Clothing process as humidity it is too big caused by glue pot, intermediate plate, numb piece, coating weight gain is inhomogenous phenomena such as.
To achieve the goals above, the technical solution of the disclosure are as follows:
A kind of preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition, by the aqueous of total pharmaceutic adjuvant
Amount improves 5.5~7.0wt.%, carries out dry granulation after Vardenafil hydrochloric acid trihydrate and Nei Jia pharmaceutic adjuvant are mixed, will
The particle and additional pharmaceutic adjuvant mixing, tabletting, coating that dry granulation obtains, obtain Vardenafil hydrochloric acid piece；It is wherein total medicinal
Auxiliary material includes interior plus pharmaceutic adjuvant and additional pharmaceutic adjuvant.
The disclosure is found after study, when the intrinsic water content of pharmaceutic adjuvant is improved 5.5~7.0wt.%, can be improved
The stability of Vardenafil hydrochloric acid trihydrate pharmaceutical composition avoids Vardenafil hydrochloric acid trihydrate in dry granulation, pressure
The crystallization water is lost in piece, coating process.
The disclosure has the beneficial effect that
The disclosure is using Vardenafil hydrochloric acid trihydrate as main component, using the side for improving the intrinsic water content of pharmaceutic adjuvant
Formula, so that preparation dry granulation, tabletting, Vardenafil hydrochloric acid trihydrate is constantly in stable state in coating process, it will not
The crystallization water is lost, the stability of Vardenafil hydrochloric acid trihydrate pharmaceutical composition is improved, while being effectively prevented to keep
Vardenafil hydrochloric acid trihydrate tablet coating process, which introduces, glues pot phenomenon caused by wet air.
Detailed description of the invention
The Figure of description for constituting a part of this disclosure is used to provide further understanding of the disclosure, and the disclosure is shown
Meaning property embodiment and its explanation do not constitute the improper restriction to the disclosure for explaining the disclosure.
Fig. 1 is dissolution curve of the Vardenafil hydrochloric acid piece of the preparation of the embodiment of the present disclosure 1~4 in pH6.8 dissolution medium
Comparison diagram；
Fig. 2 is dissolution curve of the Vardenafil hydrochloric acid piece of the preparation of the embodiment of the present disclosure 1~4 in pH1.0 dissolution medium
Comparison diagram；
Fig. 3 is dissolution curve of the Vardenafil hydrochloric acid piece of the preparation of the embodiment of the present disclosure 1~4 in pH4.5 dissolution medium
Comparison diagram；
Fig. 4 is dissolution curve comparison of the Vardenafil hydrochloric acid piece of the preparation of the embodiment of the present disclosure 1~4 in water dissolution medium
Figure.
Specific embodiment
It is noted that described further below be all exemplary, it is intended to provide further instruction to the disclosure.Unless another
It indicates, all technical and scientific terms used herein has usual with disclosure person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to the illustrative embodiments of the disclosure.As used herein, unless the context clearly indicates otherwise, otherwise singular
Also it is intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, device, component and/or their combination.
It is introduced in coating process in view of Vardenafil hydrochloric acid piece caused by wet air and glues pot, intermediate plate, numb piece, coating
It increases weight phenomena such as inhomogenous, the present disclosure proposes a kind of preparation sides of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition
Method.
A kind of exemplary embodiment of the disclosure provides a kind of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition
The water content of total pharmaceutic adjuvant is improved 5.5~7.0wt.% by the preparation method of object, by Vardenafil hydrochloric acid trihydrate and interior
Dry granulation is carried out after adding pharmaceutic adjuvant to mix, the particle that dry granulation is obtained and additional pharmaceutic adjuvant mixing, tabletting, packet
Clothing obtains Vardenafil hydrochloric acid piece；Wherein total pharmaceutic adjuvant includes interior plus pharmaceutic adjuvant and additional pharmaceutic adjuvant.
The it is proposed of the disclosure is proposed based on CN 1681481A, and the disclosed invention people has found in the course of the research, is being wrapped
After tablet is made in clothing, viscous pot, intermediate plate, numb piece, phenomena such as coating weight gain is inhomogenous can be usually generated.After further research, it produces
The reason of this raw phenomenon is caused by preparation coating process introduces wet air.Due to three water in tablet coating process
Closing object can partially or completely be dehydrated, and the pharmaceutical activity of active constituent is caused to reduce, thus the purpose for introducing humid air is by portion
The Vardenafil hydrochloric acid for dividing or being dehydrated completely is hydrated into trihydrate again.It is hydrated into three again in order to solve to introduce humid air
Hydrate be also easy to produce viscous pot, intermediate plate, numb piece, coating weight gain is inhomogenous phenomena such as contradiction, the disclosed invention people think how
Guarantee that stability of the trihydrate in coating process is key, that is, avoids the dehydration of trihydrate.
The disclosure is found after study, when the intrinsic water content of pharmaceutic adjuvant is improved 5.5~7.0wt.%, can be improved
The stability of Vardenafil hydrochloric acid trihydrate pharmaceutical composition avoids Vardenafil hydrochloric acid trihydrate in dry granulation, pressure
The crystallization water is lost in piece, coating process.If the intrinsic water content of pharmaceutic adjuvant is lower, three water of part Vardenafil hydrochloric acid will lead to
Close object dehydration, and if the intrinsic water content of pharmaceutic adjuvant it is higher when, the crystal form of Vardenafil hydrochloric acid trihydrate can be destroyed, thus shadow
Ring drug effect.
In one or more embodiments of the embodiment, interior plus pharmaceutic adjuvant water content is improved into 5.5~7.0wt.%.
Interior plus pharmaceutic adjuvant is directly mixed with Vardenafil hydrochloric acid trihydrate, when that interior pharmaceutic adjuvant water content will be added to be promoted,
It can preferably guarantee the stability of Vardenafil hydrochloric acid trihydrate.
In one or more embodiments of the embodiment, total pharmaceutic adjuvant includes microcrystalline cellulose, the poly- dimension of crosslinking
Ketone, colloidal silicon dioxide, lubricant.
In one or more embodiments of the embodiment, interior dosing auxiliary material include microcrystalline cellulose, crospovidone,
Colloidal silicon dioxide；Additional pharmaceutic adjuvant includes lubricant.
In the series embodiment, lubricant is magnesium stearate.
In the series embodiment, additional pharmaceutic adjuvant includes microcrystalline cellulose.
In the series embodiment, the water content of microcrystalline cellulose is improved into 5.5~7.0wt.%.With crospovidone, glue
State silica, lubricant are compared, and are humidified into microcrystalline cellulose, can guarantee that the water content of pharmaceutic adjuvant keeps stablizing not
Become, to be further ensured that the stability of Vardenafil hydrochloric acid trihydrate.
In the series embodiment, the water content of a part of microcrystalline cellulose is improved, another part microcrystalline cellulose it is aqueous
Measure it is constant, water content improve microcrystalline cellulose and the constant microcrystalline cellulose of water content mass ratio be not less than 7:3.Pass through reality
It tests and shows under this condition, can guarantee the stability of Vardenafil hydrochloric acid trihydrate.
In the series embodiment, a part of the constant microcrystalline cellulose of water content is as interior plus pharmaceutic adjuvant, another portion
It is allocated as additional pharmaceutic adjuvant.
In one or more embodiments of the embodiment, the mode of water content is improved as atomization plus water.Which can
Guarantee uniformity of the moisture in pharmaceutic adjuvant.
In order to enable those skilled in the art can clearly understand the technical solution of the disclosure, below with reference to tool
The technical solution of the disclosure is described in detail in the embodiment of body.
Composition in the present embodiment is consistent with former triturate (Ai Lida) prescription.
Embodiment 1
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 1.
Table 1
Preparation method:
(1) microcrystalline cellulose is taken, is placed in wet granulator, atomization plus water prepare the high-moisture to conform to quality requirements
Microcrystalline cellulose (humidification, loss on drying 6.9wt.%), then sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (humidification), crosslinking gather
Ketone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional magnesium stearate of prescription ratio are mixed, tabletting, coating are to get Vardenafil hydrochloric acid
Piece.
Embodiment 2
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 2.
Table 2
Preparation method:
(1) microcrystalline cellulose is taken, is placed in wet granulator, atomization plus water prepare the high-moisture to conform to quality requirements
Microcrystalline cellulose (humidification, loss on drying 5.5wt.%), then sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (humidification), crosslinking gather
Ketone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional magnesium stearate of prescription ratio are mixed, tabletting, coating are to get Vardenafil hydrochloric acid
Piece.
Embodiment 3
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 3.
Table 3
Preparation method:
(1) microcrystalline cellulose is taken, is placed in wet granulator, atomization plus water prepare the high-moisture to conform to quality requirements
Microcrystalline cellulose (humidification, loss on drying 6.9wt.%), then sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (humidification), crystallite are fine
Plain (routine), crospovidone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional magnesium stearate of prescription ratio are mixed, tabletting, coating are to get Vardenafil hydrochloric acid
Piece.
Embodiment 4
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 4.
Table 4
Preparation method:
(1) microcrystalline cellulose is taken, is placed in wet granulator, atomization plus water prepare the high-moisture to conform to quality requirements
Microcrystalline cellulose (humidification, loss on drying 6.9wt.%), then sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (humidification), crystallite are fine
Plain (routine), crospovidone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional microcrystalline cellulose (routine) of prescription ratio, magnesium stearate are mixed, tabletting, coating,
Up to Vardenafil hydrochloric acid piece.
Comparative example 1
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 5.
Table 5
Preparation method:
(1) microcrystalline cellulose is taken, sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (routine), crosslinking gather
Ketone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional magnesium stearate of prescription ratio are mixed, tabletting, coating are to get Vardenafil hydrochloric acid
Piece.
Comparative example 2
Vardenafil hydrochloric acid tablet recipe: specification 20mg (in terms of Vardenafil), recipe quantity are 1000, as shown in table 1.
Table 1
Preparation method:
(1) microcrystalline cellulose is taken, is placed in wet granulator, atomization plus water prepare the high-moisture to conform to quality requirements
Microcrystalline cellulose (humidification, loss on drying 8.0wt.%), then sealing is placed one day, spare；
(2) Vardenafil hydrochloric acid trihydrate is weighed according to prescription ratio and Nei Jia microcrystalline cellulose (humidification), crosslinking gather
Ketone, colloidal silicon dioxide are tieed up, dry granulation is carried out；
(3) gained particle and the additional magnesium stearate of prescription ratio are mixed, tabletting, coating are to get Vardenafil hydrochloric acid
Piece.
Experimental example 1
Moisture comparison: embodiment 1 is to make the sample of the microcrystalline cellulose preparation of theoretical moisture content high (6.9wt.%) by oneself,
Embodiment 2 is to make the sample of the microcrystalline cellulose preparation of theoretical moisture content low (5.5wt.%) by oneself.Embodiment 3 and embodiment 4
Partially to make the sample for preparing after high-moisture microcrystalline cellulose and the mixing of part conventional microcrystalline cellulose by oneself, wherein microcrystalline cellulose
High humidity and conventional ratio are 7:3, and 4 difference from Example 3 of embodiment is that conventional microcrystalline cellulose in part is additional, and outer dosage is
The 1/10 of microcrystalline cellulose total amount.Comparative example 1 is the sample of conventional microcrystalline cellulose (3.6wt.%) preparation, and comparative example 2 is certainly
Make the sample of the microcrystalline cellulose preparation of theoretical moisture content high (8.0wt.%).
1~4 sample of Example, Comparative Examples 1 and 2 sample, according to aquametry (Chinese Pharmacopoeia version general rule 0832 in 2015
First method), moisture content cannot be less than 5.5% (JX20160197 import drugs registered standard).It the results are shown in Table 5.
The result shows that embodiment 1 and the embodiment 2 sample moisture with self-control high-moisture microcrystalline cellulose preparation meet mark
Alignment request；The sample moisture that embodiment 3 and embodiment 4 are used in mixed way high humidity and conventional microcrystalline cellulose (7:3), which complies with standard, to be wanted
It asks.The sample of moisture qualification may be obtained by adjusting high humidity and conventional microcrystalline cellulose ratio.The routine of comparative example 1
The sample of microcrystalline cellulose preparation, moisture content are unqualified；Comparative example 2 samples with self-control high-moisture microcrystalline cellulose preparation
Product, moisture content is qualified, but since material moisture is larger, causes tableting processes sticking.
Table 5: determination of moisture result
| Sample | Material theoretical water content (%) | The practical water content of preparation (%) |
| Embodiment 1 | 6.83 | 6.105 |
| Embodiment 2 | 5.72 | 5.585 |
| Embodiment 3 | 6.05 | 5.752 |
| Embodiment 4 | 6.05 | 5.621 |
| Comparative example 1 | 4.20 | 3.767 |
| Comparative example 2 | 7.72 | 6.926 |
Experimental example 2
Dissolution curve comparison: 1~4 sample of Example, Comparative Examples 1 and 2 sample, according to dissolution rate and drug release determination method (in
Four general rules of state's pharmacopeia version in 2015,0,931 second method) dissolution curve measurement is carried out, using high performance liquid chromatography (Chinese Pharmacopoeia
Four general rules 0512 of version in 2015) carry out dissolution quantitative determination.
The result shows that only dissolving out ratio with the sample of self-control high-moisture microcrystalline cellulose preparation by comparative example 1~4
The sample dissolution for being used in mixed way high humidity and conventional microcrystalline cellulose (7:3) is slow, and the embodiment dissolution of Extra Section conventional microcrystalline is most
Fastly；The similar factors f of Examples 1 to 4, comparative example 2 and former triturate (Ai Lida) dissolution curve in pH6.8 dissolution medium2
50 are all larger than, it is similar to the dissolved corrosion of former triturate (Ai Lida)；Comparative example 1 and former triturate (Ai Lida) are molten in pH6.8
Out in medium dissolution curve similar factors f2It is dissimilar with the dissolved corrosion of former triturate (Ai Lida) less than 50；Embodiment 1
~4, Comparative Examples 1 and 2 sample and original triturate (Ai Lida) dissolution curve 15min in pH1.0, pH4.5, water dissolution medium
Accumulation dissolution rate is all larger than 85%, similar to the dissolved corrosion of former triturate (Ai Lida)；It the results are shown in Table 6, FIG. 1 to FIG. 4.
Table 6: dissolution curve comparing result
In conclusion present disclose provides a kind of preparation sides of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition
Method, the Vardenafil hydrochloric acid piece prepared using method of disclosure, the quality index such as moisture, dissolution curve number of complying with standard
The Vardenafil hydrochloric acid import drugs registered standard of JX20160197, ensure that the quality of product.
The foregoing is merely preferred embodiment of the present disclosure, are not limited to the disclosure, for the skill of this field
For art personnel, the disclosure can have various modifications and variations.It is all within the spirit and principle of the disclosure, it is made any to repair
Change, equivalent replacement, improvement etc., should be included within the protection scope of the disclosure.
Claims (10)
1. a kind of preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition, characterized in that will be total medicinal auxiliary
The water content of material improves 5.5~7.0wt.%, does after Vardenafil hydrochloric acid trihydrate and Nei Jia pharmaceutic adjuvant are mixed
Method granulation, the particle that dry granulation is obtained and additional pharmaceutic adjuvant mixing, tabletting, coating, obtain Vardenafil hydrochloric acid piece；Its
In total pharmaceutic adjuvant include interior plus pharmaceutic adjuvant and additional pharmaceutic adjuvant.
2. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as described in claim 1, feature
It is that interior plus pharmaceutic adjuvant water content is improved into 5.5~7.0wt.%.
3. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as described in claim 1, feature
It is that total pharmaceutic adjuvant includes microcrystalline cellulose, crospovidone, colloidal silicon dioxide, lubricant.
4. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as described in claim 1, feature
It is that interior dosing auxiliary material includes microcrystalline cellulose, crospovidone, colloidal silicon dioxide；Additional pharmaceutic adjuvant includes lubricant.
5. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as described in claim 3 or 4, special
Sign is that lubricant is magnesium stearate.
6. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as claimed in claim 4, feature
It is that additional pharmaceutic adjuvant includes microcrystalline cellulose.
7. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as claimed in claim 4, feature
It is that the water content of microcrystalline cellulose is improved into 5.5~7.0wt.%.
8. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as claimed in claim 7, feature
It is that the water content of a part of microcrystalline cellulose improves, and the water content of another part microcrystalline cellulose is constant, and water content improves micro-
The mass ratio of crystalline cellulose and the constant microcrystalline cellulose of water content is not less than 7:3.
9. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as claimed in claim 8, feature
It is that a part of the constant microcrystalline cellulose of water content is as interior plus pharmaceutic adjuvant, and another part is as additional pharmaceutic adjuvant.
10. the preparation method of stable Vardenafil hydrochloric acid trihydrate pharmaceutical composition as described in claim 1, feature
It is to improve the mode of water content as atomization plus water.
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