CN106667943A - Tadalafil tablet - Google Patents
Tadalafil tablet Download PDFInfo
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- CN106667943A CN106667943A CN201710192409.1A CN201710192409A CN106667943A CN 106667943 A CN106667943 A CN 106667943A CN 201710192409 A CN201710192409 A CN 201710192409A CN 106667943 A CN106667943 A CN 106667943A
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- CN
- China
- Prior art keywords
- tadalafei
- tadalafil
- polyethylene glycol
- stearic acid
- tadalafil tablet
- 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.)
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to tadalafil tablets. The invention belongs to the field of a new preparation technology of medicines, and in particular relates to a preparation method of the tadalafil tablets. The tadalafil tablets provided by the invention are formed by directly tabletting tadalafil composite granules and auxiliary materials, wherein the tadalafil composite granules are prepared according to the following method: mixing and pelleting the tadalafil and a polyethylene glycol 12 hydroxystearate ethanol solution and drying ; the weight ratio of the tadalafil to the polyethylene glycol 12 hydroxystearate ethanol solution is 100:(1-50). The tadalafil tablets prepared by the method are high in in-vitro dissolution rate and stable in dissolution behavior in the long-time placing process; the production process is simple, easy to operate and high in yield ; the advantage of implementing industrialized large-scale production can be realized.
Description
Technical field
The invention belongs to medicine manufacture new technical field, and in particular to a kind of preparation method of tadalafil tablet.
Background technology
Tadalafei is the selectivity of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase enzyme 5 (PDE5), reversible inhibitor,
Treatment male erectile dysfunction.Chemical name：6- (dioxolanes -5- bases between 1,3- benzos) -2,3,6,7,12,12a- hexahydros
Change -2- methyl, (6R, 12aR)-pyrazine simultaneously [1 ' 2 '：1,6] pyrido [3,4-b] indoles -1,4- diketone.
Tadalafei is selectivity, the reversible inhibition of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase enzyme 5 (PDE5)
Agent.When sexual stimulus causes local release nitric oxide, PDE5 to be suppressed by Tadalafei, put forward cGMP levels in penis sponge body
It is high.This causes smooth muscle relaxation, blood to flow into penile tissue, produces erection.Such as without sexual stimulus, Tadalafei is not had an effect.
In vitro study shows that Tadalafei is the selective depressant of PDE5.PDE5 be present in corpus cavernosum smooth muscle, blood vessel and
Visceral smooth muscle, skeletal muscle, blood platelet, kidney, lung and a kind of IC enzyme.Effect of the Tadalafei to PDE5 compares other
The effect of phosphodiesterase is strong.Effect of the Tadalafei to PDE5 compares what is found in heart, brain, blood vessel, liver and other organs
The effect of PDE1, PDE2, PDE4 etc. is strong by 10, more than 000 times.Effect of the Tadalafei to PDE5 is compared in heart, blood vessel and found
PDE3 effect it is strong by 10, more than 000 times.Selectivity to PDE5 is critically important more than PDE3, because PDE3 and myocardial contractive power
It is relevant.Additionally, Tadalafei is nearly 700 times to PDE6 to the action intensity of PDE5, the latter is present in retina, participates in light and passes
Lead.Tadalafei is high by 10 to the action intensity comparison PDE7-10 of PDE5, more than 000 times.
Tadalafei is quick after oral to be absorbed, and median time reaches average maximum observation PC for 2 hours after medication
(Cmax).Absolute bioavailability after oral this product is not yet clear and definite.The absorptivity and degree of Tadalafei be not by the shadow of food
Ring, so this product can be with or without food with clothes.Medicine time (morning or evening) is to absorptivity and degree without clinical meaning
The impact of justice.About 63 liters of volume is evenly distributed, illustrates that Tadalafei distribution enters tissue.94% in treatment concentration, blood plasma
Tadalafei and protein combination.Protein combination is not affected by kidney function damage.In health volunteer, only less than 0.0005%
The medicine of medication dose is occurred in seminal fluid.Tadalafei is mainly by Cytochrome P450 (CYP) 3A4 isomers metabolism.Mainly
Cyclic metabolism product be glucuronic acid methyl catechol.Effect of this metabolite to PDE5 is at least weaker than Tadalafei
13,000 times.Therefore, there is no clinical activity in the Metabolites Concentration observed.It is flat in the oral Tadalafei of health volunteer
Clearance rate is 2.5L/hr, and mean half-life is 17.5 hours.Tadalafei is mainly arranged with inactive metabolite form
Let out, mainly from excrement (about 61% dosage), small part is discharged (about 36% dosage) from urine.In health volunteer, he reaches
Draw time and the dosage of non-pharmacokinetics linear.More than 2.5~20mg dosage ranges, AUC with dosage into than
Improve on example ground.Daily medication once, in 5 days steady state plasma concentration was reached.The medicine generation that patients with erectile dysfunction crowd measures
Dynamics is similar to the experimenter without erectile dysfunction.The oral Tadalafei of healthy geriatric experimenter (65 years old or more)
Clearance rate is relatively low so that health volunteers of the AUC than 19-45 year is high by 25%.The impact at this age, and need not without clinical meaning
Adjustment dosage.In single dose Tadalafei (5~20mg) clinical pharmacology research, the exposed amount (AUC) of Tadalafei is light
Degree (51~80ml/min of CrCl) or moderate (31~50ml/min of CrCl) potential renal insufficiency patient and ephrosis
Late period increases about one times in the patient using dialysis.Observe in the patient of haemodialysis, Cmax is higher than health volunteer
41%.Removing of the haemodialysis to Tadalafei helps little.In slight and moderate hepatic disorder experimenter (Child-Pugh
A and B levels), the AUC of Tadalafei is similar to health volunteer.Therefore need not adjustment dosage.With regard to severe dyshepatia
(Child-Pugh is classified C) patient uses the clinical safety Limited information of this product；If prescribed to such patient, place is needed
Fang doctor carries out conscientious interests/risk assessment to every patient.To the patient of dyshepatia daily more than 10mg he
The situation of Da Lafei, there is no at present data.
Tadalafei is in white powder, odorless, tasteless, water insoluble and alcohols solvent.Tadalafei is BCSII classes
Compound, dissolubility difference directly affects the In Vitro Dissolution and body absorption of medicine, dissolubility difference be affect the key of clinical efficacy because
Element.Now technology is solved for the technology barrier of Tadalafei dissolubility difference using various methods reduction tadalafil particle diameter
Certainly, such as solid dispersion, raw material micronizing, but there is complex process, the technological deficiency of inefficiency.
By Tadalafei and medicine in the preparation method and its pharmaceutical preparation of CN105496965A Tadalafei solid dispersions
After acceptable carrier is well mixed on, plus heat fusing, then cool down, crushing obtains Tadalafei solid dispersions.This technology
Using solid dispersion technology, Tadalafei can be made to be present in carrier in the way of solid solution, then again row is crushed, and be can reach micro-
Particle diameter Tadalafei, but complex process, and adding heat fusing and crushing process to consume mass energy and be unfavorable for industrialized production.
Tadalafei is present in carrier in the way of solid solution, and the Tadalafei of its unformed state can be in stability placement process
In be changed into the Tadalafei of crystalline state, so as to form dissolution downward trend.
Using α-hydroxypropylβ-cyclodextrin and ethyl in a kind of pharmaceutical compositions containing Tadalafei of CN105380912A
Mode that cellulose is included to Tadalafei solubilising, this kind of mode has that Tadalafei utilization rate during inclusion is low, α-
The big shortcoming of hydroxypropylβ-cyclodextrin and ethyl cellulose consumption.
The oral drug preparation of CN104274417A Tadalafeis carries out solubilising using water soluble polymer, and this technology is using solid
Body dispersion technology, can be such that Tadalafei is present in the way of solid solution in water soluble polymer, dried coating film, its unformed shape
The Tadalafei of state can be changed into the Tadalafei of crystalline state in stability placement process, so as to form dissolution downward trend.
Therefore the preparation method for developing the stable tadalafil piece of a kind of process is simple, dissolution is extremely urgent.
The content of the invention
In view of the deficiencies in the prior art, it is an object of the invention to be studied by lot of experiments, there is provided a kind of process is simple,
The stable tadalafil piece preparation method of efficiency high, high income, dissolution.
The purpose of the present invention is that below scheme is realized：
A kind of tadalafil tablet, is formed by Tadalafei composition grain with auxiliary material direct tablet compressing；Described Tadalafei
Composition grain is prepared as follows forming：Tadalafei is mixed into system with the hydroxy stearic acid ester ethanol solution of polyethylene glycol 12
Grain, is dried；Tadalafei is 100 with the weight ratio of the hydroxy stearic acid ester of polyethylene glycol 12:1-50.It is preferred that Tadalafei and poly- second
The weight ratio of the hydroxy stearic acid ester of glycol 12 is 100:5.
The accessory package of tadalafil tablet is containing filler and lubricant.Filler is selected from lactose, starch, microcrystalline cellulose, sweet
One or more in dew alcohol, dextrin, pregelatinized starch, calcium sulfate, calcium monohydrogen phosphate and calcium carbonate.It is preferred that lactose
The lubricant of tadalafil tablet is in magnesium stearate, superfine silica gel powder, stearic acid, talcum powder, Compritol 888 ATO
One or more.
The preparation method of tadalafil tablet is comprised the steps of：By Tadalafei and the hydroxy stearic acid ester second of polyethylene glycol 12
Alcoholic solution mixing granulation, is dried, and forms with auxiliary material direct tablet compressing.
Tadalafil tablet according to prepared by the preparation method of above-mentioned tadalafil tablet.
Compared with prior art, particulate footpath Tadalafei preparation method according to the present invention has the advantage that and significantly enters
Step：(1) Tadalafei In Vitro Dissolution is high, and dissolved corrosion is stablized in long-term placement process；(2) simple production process, it is easy to operate, receive
Rate is high, it is possible to achieve the big production of industrialization.
Description of the drawings
Fig. 1 is embodiment 4~6, embodiment 11, the tadalafil tablet accumulation dissolution of the preparation of CN105496965A embodiments 1
Write music line chart
Fig. 2 is embodiment 4~6, embodiment 11, the tadalafil tablet long term test 6 of the preparation of CN105496965A embodiments 1
Month accumulation Dissolution profiles figure
Specific embodiment
The characteristics of tadalafil tablet that the present invention is obtained has process is simple, efficiency high, high income.Hereinafter implement explanation originally
Invention, but the present invention is limited never in any form.
Embodiment 1
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 0.2g |
| Ethanol | 3.8g |
| Microcrystalline cellulose | 25g |
| Lactose | 200g |
| Hydroxypropyl methyl cellulose sodium | 5g |
| Ac-Di-Sol | 5g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 5% hydroxy stearic acid ester ethanol of polyethylene glycol 12
100 mesh sieves are crossed in solution mixing system grain, 60 DEG C of dryings, add microcrystalline cellulose, lactose, the hydroxypropyl methyl cellulose of recipe quantity
Sodium, Ac-Di-Sol mixing 30min, add the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 2
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 0.5g |
| Ethanol | 2g |
| Starch | 25g |
| Lactose | 200g |
| Hydroxypropyl methyl cellulose sodium | 8g |
| Ac-Di-Sol | 5g |
| Magnesium stearate | 2g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 20% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add starch, lactose, hydroxypropyl methyl cellulose sodium, the friendship of recipe quantity
Connection sodium carboxymethylcellulose mixing 30min, adds the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 3
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 1g |
| Ethanol | 4g |
| Pregelatinized starch | 150g |
| Dextrin | 50g |
| Hydroxypropyl methyl cellulose sodium | 2g |
| Ac-Di-Sol | 10g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 20% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add pregelatinized starch, dextrin, the hydroxypropyl methyl fiber of recipe quantity
Plain sodium, Ac-Di-Sol mixing 30min, add the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 4
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 1g |
| Ethanol | 9g |
| Lactose | 200g |
| Hydroxypropyl methyl cellulose sodium | 2g |
| Ac-Di-Sol | 10g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 10% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add lactose, the Ac-Di-Sol mixing of recipe quantity
30min, adds the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 5
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 1g |
| Ethanol | 4g |
| Lactose | 200g |
| Hydroxypropyl methyl cellulose sodium | 2g |
| Sodium carboxymethyl starch | 5g |
| Superfine silica gel powder | 1g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 20% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add lactose, hydroxypropyl methyl cellulose sodium, the carboxymethyl of recipe quantity
Sodium starch, Ac-Di-Sol mixing 30min, add superfine silica gel powder, the magnesium stearate mixing 5min of recipe quantity, pressure
Piece, obtains final product.
Embodiment 6
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 1g |
| Ethanol | 4g |
| Lactose | 200g |
| Carboxymethyl cellulose sodium | 3g |
| Sodium carboxymethyl starch | 5g |
| Superfine silica gel powder | 1g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 20% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add lactose, carboxymethyl cellulose sodium, the sodium carboxymethyl starch of recipe quantity
Mixing 30min, adds superfine silica gel powder, the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 7
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 2g |
| Ethanol | 4g |
| Starch | 50g |
| Mannitol | 150g |
| Hydroxypropyl methyl cellulose sodium | 15g |
| Ac-Di-Sol | 10g |
| Magnesium stearate | 2g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 33% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add the starch of recipe quantity, mannitol, hydroxypropyl methyl cellulose sodium,
Ac-Di-Sol mixing 30min, adds the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 8
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 4g |
| Ethanol | 8g |
| Starch | 50g |
| Calcium monohydrogen phosphate | 20g |
| Calcium sulfate | 20 |
| Lactose | 100 |
| Hydroxypropyl methyl cellulose sodium | 15g |
| Ac-Di-Sol | 10g |
| Magnesium stearate | 2g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 33% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add starch, calcium monohydrogen phosphate, calcium sulfate, lactose, the hydroxypropyl of recipe quantity
Ylmethyl sodium cellulosate, Ac-Di-Sol mixing 30min, the magnesium stearate mixing 5min of addition recipe quantity, compressing tablet,
Obtain final product.
Embodiment 9
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| The hydroxy stearic acid ester of polyethylene glycol 12 | 8g |
| Ethanol | 8g |
| Microcrystalline cellulose | 150g |
| Mannitol | 20g |
| Dextrin | 20g |
| Calcium carbonate | 50g |
| Hydroxypropyl methyl cellulose sodium | 5g |
| Ac-Di-Sol | 15g |
| Superfine silica gel powder | 2g |
| Stearic acid | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 50% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add the microcrystalline cellulose of recipe quantity, mannitol, dextrin, calcium carbonate,
Hydroxypropyl methyl cellulose sodium, Ac-Di-Sol mixing 30min, add the superfine silica gel powder of recipe quantity, stearic acid to mix
5min is closed, compressing tablet is obtained final product.
Embodiment 10
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei and the 50% hydroxy stearic acid ester second of polyethylene glycol 12
100 mesh sieves are crossed in alcoholic solution mixing granulation, 60 DEG C of dryings, add microcrystalline cellulose, lactose, dextrin, the hydroxypropyl methyl of recipe quantity
Sodium cellulosate, Ac-Di-Sol mixing 30min, add talcum powder, the Compritol 888 ATO mixing 5min of recipe quantity,
Compressing tablet, obtains final product.
Embodiment 11
| Tadalafei (Tadalafei raw material particle size D90 is 64.53 μm) | 20g |
| Lactose | 200g |
| Hydroxypropyl methyl cellulose sodium | 2g |
| Ac-Di-Sol | 10g |
| Magnesium stearate | 1g |
Tadalafil tablet (specification：20mg) preparation method：By Tadalafei, lactose, Ac-Di-Sol mixing
30min, adds the magnesium stearate mixing 5min of recipe quantity, compressing tablet to obtain final product.
Embodiment 12
The tadalafil tablet sample prepared using embodiment 4~6, embodiment 11, CN105496965A embodiments 1 is taken, is adopted
With following method measure and calculation accumulation Tadalafei dissolution rate and long term test June accumulation Tadalafei dissolution rate, measurement result
It is shown in Table 1, table 2.
Dissolution testing conditions：
Dissolution medium：The aqueous solution containing 0.05% lauryl sodium sulfate
Medium volume：1000ml
Rotating speed：50rpm
Chromatographic condition and system suitability：
Chromatographic column：Octyl silane group silica gel is filler
Mobile phase：The trifluoroacetic acid solution of acetonitrile -0.1% (45:55)
Flow velocity：1.0ml/min
Column temperature：40℃
Detection wavelength：285nm
Sample size：20μl
It is prepared by solution：
Reference substance solution：Tadalafei reference substance about 10mg is weighed, it is accurately weighed, in putting 100ml measuring bottles, mixed with flowing
Scale is solved and be diluted to, is shaken up, precision is measured during 4ml (20mg specifications) puts 20ml measuring bottles, and with dissolution medium scale is diluted to, and is shaken
It is even, as Tadalafei reference substance solution.
Tadalafei reference substance specifying information is as follows：
| Sample ID | Lot number | Assignment | Packing specification | Source |
| Tadalafei reference substance | WS/TDF/2013 | 99.8% | 0.5g/ bottles | SMS Pharmaceuticals Ltd |
Need testing solution：Dissolution fluid 10ml is taken, is filtered, subsequent filtrate is used as need testing solution.
Assay method：
Take this product each 12, according to dissolution method (Chinese Pharmacopoeia two annex X the second methods of C of version in 2010), with
0.5% sodium dodecyl sulfate solution 1000ml is dissolution medium, and rotating speed is 50pm, is operated in accordance with the law, respectively at 5,10,15,30,
Solution 10ml (while adding equality of temperature solvent 10ml) is taken during 45min, is filtered, subsequent filtrate is used as need testing solution；Separately weigh him to reach
Draw non-control product appropriate (about 10mg), it is accurately weighed, in putting 100ml measuring bottles, plus flow and phased soln and be diluted to scale, shake up,
Precision measures 4ml and puts in 20ml measuring bottles, plus mobile phase is diluted to scale, shakes up, used as reference substance solution.Precision measures test sample
Solution and each 20 μ l of reference substance solution, are injected separately into liquid chromatograph, record chromatogram.Accumulation dissolution rate is calculated by external standard method.
Computing formula：
Stripping quantity (%)=AX × f × 1000/Mx × 100%
In formula：AX is the peak area of need testing solution；
F=mR × R/AR/VR；
MXFor the labelled amount of tadalafil tablet, mg；
MR is the reference substance amount of weighing, mg；
R for reference substance itself content, %；
AR is the peak area of reference substance solution；
VR is that reference substance solution dilutes volume, ml.
Tadalafil tablet accumulation dissolution rate prepared by the embodiment 4~6 of table 1, embodiment 11, CN105496965A embodiments 1
The long-term June accumulation of tadalafil tablet prepared by the embodiment 4~6 of table 2, embodiment 11, CN105496965A embodiments 1
Dissolution rate
Claims (8)
1. a kind of tadalafil tablet, it is characterised in that：Formed with auxiliary material direct tablet compressing by Tadalafei composition grain；Described
Tadalafei composition grain is prepared as follows forming：Tadalafei is molten with the hydroxy stearic acid ester ethanol of polyethylene glycol 12
Liquid mixing granulation, is dried；Tadalafei is 100 with the weight ratio of the hydroxy stearic acid ester of polyethylene glycol 12:1-50.
2. tadalafil tablet according to claim 1, it is characterised in that：Tadalafei and the hydroxy stearic acid of polyethylene glycol 12
The weight ratio of ester is 100:5.
3. the tadalafil tablet according to any one of claim 1-2, it is characterised in that：Described accessory package containing filler and
Lubricant.
4. tadalafil tablet according to claim 3, it is characterised in that：Described filler is selected from lactose, starch, crystallite
One or more in cellulose, mannitol, dextrin, pregelatinized starch, calcium sulfate, calcium monohydrogen phosphate and calcium carbonate.
5. tadalafil tablet according to claim 4, it is characterised in that：Described filler is lactose.
6. tadalafil tablet according to claim 5, it is characterised in that：Described lubricant is magnesium stearate, micro mist silicon
One or more in glue, stearic acid, talcum powder, Compritol 888 ATO.
7. a kind of preparation method of the tadalafil tablet according to any one of claim 1-6, it is characterised in that comprising following
Step：By Tadalafei and the hydroxy stearic acid ester ethanol solution mixing granulation of polyethylene glycol 12, be dried, with auxiliary material direct tablet compressing and
Into.
8. the tadalafil tablet prepared by the preparation method of tadalafil tablet according to claim 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710192409.1A CN106667943A (en) | 2017-03-28 | 2017-03-28 | Tadalafil tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710192409.1A CN106667943A (en) | 2017-03-28 | 2017-03-28 | Tadalafil tablet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106667943A true CN106667943A (en) | 2017-05-17 |
Family
ID=58826510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710192409.1A Pending CN106667943A (en) | 2017-03-28 | 2017-03-28 | Tadalafil tablet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106667943A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012107541A1 (en) * | 2011-02-10 | 2012-08-16 | Synthon Bv | Pharmaceutical composition comprising tadalafil and a cyclodextrin |
-
2017
- 2017-03-28 CN CN201710192409.1A patent/CN106667943A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012107541A1 (en) * | 2011-02-10 | 2012-08-16 | Synthon Bv | Pharmaceutical composition comprising tadalafil and a cyclodextrin |
Non-Patent Citations (1)
| Title |
|---|
| 姚欣: "聚乙二醇-12-羟基硬脂酸酯对尼莫地平体外溶出及口服吸收的影响", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
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Application publication date: 20170517 |