A kind of pharmaceutical composition containing Suo Feibuwei
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of pharmaceutical composition containing Suo Feibuwei and its tablet
Preparation method.
Background technology
Hepatitis C(Hepatitis)Come from HCV(HCV)Infection, mainly passes through contact infection person's blood born.Third
Liver can be divided into it is acute with it is chronic.Acute hepatitis c virus infection refers to the acute disease in initial 6 months after hepatitis c virus infection.For
For most people, acute infection generally translates into chronic infection.Chronic hepatitis C virus infection refers to that hepatitis C virus is deposited for a long time
The chronic disease stayed in human body.Hepatitis c virus infection can cause serious liver diseases, such as hepatic sclerosis and liver with even lifelong
Cancer.75%~85% can develop into chronic hepatitis C virus infection in hepatitis c virus infection person, and 60%~70% can develop into chronic liver disease,
5%~20% can develop into hepatic sclerosis between 20 to 30 years, and 1%~5% can die from hepatic sclerosis or liver cancer.
Treatment currently for hepatitis is mainly the use in conjunction of a variety of antiviral drugs.In December, 2013 in U.S.
The medicine Suo Feibuwei (Sofosbuvir) of state's Initial Public Offering, chemical name are N- [[P (S), 2 ' R] -2 '-deoxidations -2 '-fluoro-
2 '-methyl-P- phenyl -5 '-uridine acyl group]-L- isopropyl propionates, molecular formula: C22H29FN3O9P, it is that a kind of white is extremely or white
Color crystalline solid, is slightly soluble in water.
Suo Feibuwei is a kind of NS5B AG14361s, is without the use of interferon to the HCV of some genotype, can
Side effect is reduced, there is the effect of good.
The content of the invention
, should the medicine containing Suo Feibuwei it is an object of the invention to provide a kind of new pharmaceutical composition containing Suo Feibuwei
The stability of compositions is good, and dissolution rate is good.
It is another object of the present invention to provide a kind of preparation method of the pharmaceutical composition containing Suo Feibuwei, the party
Method is adapted to industrial production.
Specifically, the invention provides:
A kind of pharmaceutical composition containing Suo Feibuwei, contains:Suo Feibuwei, filler, surfactant.
The described pharmaceutical composition containing Suo Feibuwei is tablet.
The described pharmaceutical composition containing Suo Feibuwei, the weight ratio of each component are:
The parts by weight of Suo Feibuwei 30 ~ 50
The parts by weight of surfactant 3 ~ 5
The parts by weight of filler 30 ~ 60.
The one kind of described filler in microcrystalline cellulose, Lactis Anhydrous, amylum pregelatinisatum, PVP, mannitol
It is or several.
Described filler is the composition that PVP and mannitol form, and more preferably weight ratio is 1:(5~8)
PVP and mannitol composition composition.
Shown surfactant is lauryl sodium sulfate.
The described pharmaceutical composition containing Suo Feibuwei prepares piece agent, and its preparation method comprises the following steps:
(1) stirred after mixing Suo Feibuwei, surfactant, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with filler, direct tablet compressing, get Suo Feibuwei tablets.
The present invention has the advantages that compared with prior art:
1st, product stability of the invention is good, and dissolution is complete.
2nd, operation is simple for production of the invention, is suitable for industrial production.
The content of the invention
, should the medicine containing Suo Feibuwei it is an object of the invention to provide a kind of new pharmaceutical composition containing Suo Feibuwei
The stability of compositions is good, and dissolution rate is good.
It is another object of the present invention to provide a kind of preparation method of the pharmaceutical composition containing Suo Feibuwei, the party
Method is adapted to industrial production.
Specifically, the invention provides:
A kind of pharmaceutical composition containing Suo Feibuwei, contains:Suo Feibuwei, filler, surfactant.
The described pharmaceutical composition containing Suo Feibuwei is tablet.
The described pharmaceutical composition containing Suo Feibuwei, the weight ratio of each component are:
The parts by weight of Suo Feibuwei 30 ~ 50
The parts by weight of surfactant 3 ~ 5
The parts by weight of filler 30 ~ 60.
The one kind of described filler in microcrystalline cellulose, Lactis Anhydrous, amylum pregelatinisatum, PVP, mannitol
It is or several.
Described filler is the composition that PVP and mannitol form, and more preferably weight ratio is 1:(5~8)
PVP and mannitol composition composition.
Shown surfactant is lauryl sodium sulfate.
The described pharmaceutical composition containing Suo Feibuwei prepares piece agent, and its preparation method comprises the following steps:
(1) stirred after mixing Suo Feibuwei, surfactant, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with filler, direct tablet compressing, get Suo Feibuwei tablets.
The present invention has the advantages that compared with prior art:
1st, product stability of the invention is good, and dissolution is complete.
2nd, operation is simple for production of the invention, is suitable for industrial production.
Embodiment
Below by way of the description of embodiment, the invention will be further described, but this is not the limit to the present invention
System, those skilled in the art according to the present invention basic thought, various modifications may be made or improve, but without departing from this
The basic thought of invention, within the scope of the present invention.
Suo Feibu Wiegands are according to U.S. Patent Publication No.:It is prepared by 2010/0298257 and 2100/0251152 methods described.
Test method
Relevant material takes this product 25mg, accurately weighed, puts in 25mL measuring bottles, adds dilution【Water-acetonitrile(80:20), under
Together】Dissolve and be diluted to scale, shake up, as need testing solution.Precision measures in right amount, is quantitatively diluted and is made often with dilution
Containing about the μ g of Suo Feibuwei 1 solution in 1ml, as contrast solution.According to high performance liquid chromatography(Chinese Pharmacopoeia version two in 2010
Annex V D)Experiment, is filler with octadecylsilane chemically bonded silica(4.6 × 250mm, 5 μm), with 10mmol/L di(2-ethylhexyl)phosphates
Hydrogen potassium solution(Phosphoric acid adjusts pH to 3.0)- acetonitrile(80:20)For mobile phase A, with acetonitrile-methanol(80:20)For Mobile phase B, press
Table carries out gradient elution;Column temperature is 30 °C, and flow velocity is 1.0ml per minute, Detection wavelength 260nm.The μ l of contrast solution 10 are taken, are noted
Enter liquid chromatograph, adjust detection sensitivity, the peak height for making principal component chromatographic peak is about the 10% of full scale, then precision measures confession
Each 10 μ l of test sample solution, liquid chromatograph is injected, record chromatogram.It is single if any impurity peaks in the chromatogram of need testing solution
Impurity peak area cannot be greater than contrast solution main peak area(0.1%), each impurity peaks peak area and cannot be greater than contrast solution master
10 times of the peak area at peak(1.0%).
Dissolution rate takes this product, according to dissolution method(Chinese Pharmacopoeia two annex X the second methods of C of version in 2010), with water
900ml is dissolution medium, and rotating speed is 50 turns per minute, is operated in accordance with the law, during through 10 minutes, takes solution to filter, according to assay item
Under chromatographic condition, precision measures the μ l of subsequent filtrate 20, injects liquid chromatograph, records chromatogram.Suo Feibuwei reference substances separately are taken,
Accurately weighed, be dissolved in water and quantify the solution for diluting and being made in every 1ml containing about 0.1mg, is measured in the same method.By external standard method with peak face
Product calculates the stripping quantity of every.
【Assay】According to high performance liquid chromatography(Two D of annex V of Chinese Pharmacopoeia version in 2010)Measure.
Chromatographic condition is filler with octadecylsilane chemically bonded silica with system suitability(4.6 × 250mm, 5 μ
m), with water-acetonitrile(60:40)For mobile phase, column temperature is 30 °C, and flow velocity is 1.0ml per minute, Detection wavelength 260nm.It is theoretical
Plate number should be not less than 3000 in terms of Suo Feibuwei.
Determination method takes this product 20, accurately weighed, and finely ground, precision weighs in right amount(It is approximately equivalent to Suo Feibuwei 100mg),
Put in 200ml measuring bottles, add mobile phase(Water-acetonitrile(80:20), similarly hereinafter)Shaking dissolves Suo Feibuwei and is diluted to scale, shakes
Even, filtration, precision measures the μ l of subsequent filtrate 10 injection liquid chromatographs, records chromatogram;Suo Feibuwei reference substances separately are taken, are surveyed with method
It is fixed.By external standard method with calculated by peak area, produce.
Test example 1:Prescription screening experiment-surfactant selection
Suo Feibuwei 40g are taken respectively(Content 99.9%, total miscellaneous 0.09%), by following prescriptions(It is shown in Table 1)It is made and contains Suo Fei
Cloth Wei piece, dissolution rate and relevant material are detected, the results are shown in Table 4:
The Suo Feibuwei prescriptions of table 3(Unit:g)
The preparation method of prescription 1:
(1) Suo Feibuwei is well mixed with microcrystalline cellulose, PVPP, obtains pulverulent solids;
(2) magnesium stearate mixes with the pulverulent solids obtained by step (1), direct tablet compressing, get Suo Feibuwei tablets.
The preparation method of prescription 2 ~ 4:
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) it is well mixed to the powder obtained by step (1) with microcrystalline cellulose, PVPP, obtains pulverulent solids;
(3) magnesium stearate mixes with the pulverulent solids obtained by step (2), tabletting, get Suo Feibuwei tablets.
The result of the test of table 2
Result of the test shows:The Suo Feibuwei Dissolution of Tablet prepared using prescription of the present invention is significantly higher than no surface-active
The prescription of agent addition, but the dissolution rate increase not in direct ratio after the amount of lauryl sodium sulfate increases to certain degree,
And there is downward trend;But add product sliver rate increase after Surfactant SDS.
Test example 2:Prescription screening experiment-filler selection
Suo Feibuwei 40g are taken respectively(Content 99.9%, total miscellaneous 0.09%), by following prescriptions(It is shown in Table 1)It is made and contains Suo Fei
Cloth Wei piece, dissolution rate and relevant material are detected, the results are shown in Table 4:
The Suo Feibuwei prescriptions of table 3(Unit:g)
The preparation method of prescription 1 ~ 3:
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) it is well mixed to the powder obtained by step (1) with filler, obtains pulverulent solids;
(3) magnesium stearate mixes with the pulverulent solids obtained by step (2), tabletting, get Suo Feibuwei tablets.
The preparation method of prescription 4 ~ 7:
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
The result of the test of table 4
Result of the test shows:The Suo Feibuwei tablets prepared using mannitol with povidone mixture as filler are split
Piece rate significantly reduces.
Test example 3:Accelerated test
The product of Example 3,5,6,8 carries out accelerated test, the results are shown in Table 3.
The Suo Feibuwei piece accelerated test data of table 4
Packaging:Commercially available back, investigate condition:40 DEG C of temperature, humidity 75%
Conclusion:Road as seen from the above table, the product prepared by the inventive method, stability under high temperature and illumination better than pair
Ratio.
Preparation example
Embodiment 1
Prescription
Suo Feibuwei 40g
Lauryl sodium sulfate 5.6g
Amylum pregelatinisatum 135g
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with amylum pregelatinisatum, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 2
Prescription
Suo Feibuwei 35g
Lauryl sodium sulfate 5.5g
Lactis Anhydrous 138g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with Lactis Anhydrous, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 3
Prescription
Suo Feibuwei 40g
Lauryl sodium sulfate 8.0g
Microcrystalline cellulose 145g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with microcrystalline cellulose, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 4
Prescription
Suo Feibuwei 45g
Lauryl sodium sulfate 6.3g
Mannitol 154g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) powder obtained by step (1) is well mixed with mannitol, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 5
Prescription
Suo Feibuwei 43g
Lauryl sodium sulfate 7.2g
Mannitol 120g
PVP 20g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 6
Prescription
Suo Feibuwei 38g
Lauryl sodium sulfate 6.4g
Mannitol 126g
PVP 16g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 7
Prescription
Suo Feibuwei 40g
Lauryl sodium sulfate 6.2g
Mannitol 125g
Mannitol 25g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with mannitol, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 8
Prescription
Suo Feibuwei 37g
Lauryl sodium sulfate 5.3g
Mannitol 124g
PVP 15g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 9
Prescription
Suo Feibuwei 20g
Lauryl sodium sulfate 4.5g
Mannitol 60g
PVP 7.5g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.
Embodiment 10
Prescription
Suo Feibuwei 4.0g
Lauryl sodium sulfate 6.1g
Mannitol 10g
PVP 3g.
Preparation method
(1) stirred after Suo Feibuwei is mixed with lauryl sodium sulfate, obtain pulverulent solids;
(2) after mannitol is well mixed by weight proportion with PVP, add thereto to the powder obtained by step (1)
End, it is well mixed, obtains pulverulent solids, direct tablet compressing, get Suo Feibuwei tablets.