CN108785273A - A kind of entecavir capsule pharmaceutical composition and preparation method thereof - Google Patents
A kind of entecavir capsule pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN108785273A CN108785273A CN201811079954.0A CN201811079954A CN108785273A CN 108785273 A CN108785273 A CN 108785273A CN 201811079954 A CN201811079954 A CN 201811079954A CN 108785273 A CN108785273 A CN 108785273A
- Authority
- CN
- China
- Prior art keywords
- entecavir
- microcrystalline cellulose
- magnesium stearate
- micronizing
- mixing
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of entecavir capsule pharmaceutical compositions and preparation method thereof.The composition includes micronizing Entecavir, micronizing magnesium stearate, pregelatinized starch and microcrystalline cellulose, and the micronizing Entecavir, micronizing magnesium stearate Size Distribution are D90It≤30 μm, is made by carrying out total micronizing after Entecavir and magnesium stearate mixing.Pharmaceutical composition stability of the present invention is good, dissolution rate is high, bioavilability is high, and formula and preparation process are simple, is suitble to industrialized production.
Description
Technical field
The invention belongs to technical field of medicine, and in particular to a kind of entecavir capsule pharmaceutical composition and its preparation
Method.
Background technology
Entecavir, English name Entecavir, chemical name are：2- amino -9- [(1S, 3R, 4S) -4- hydroxyls
Base -3- methylol -2- methylenes amyl] -1,9- dihydro -6-H- purine-6-one monohydrates.
Structural formula：
Molecular formula：C12H15N5O3·H2O, molecular weight：295.3.
Entecavir is guanosine analog, is the anti-hepatitis B disease developed by Bristol-Myers Squibb Co. of the U.S.
Cytotoxic drug clinically is used to treat the chronic hepatitis B of adult, including hepatitis virus replication activity rises, blood plasma transfer ammonia
Enzyme (ALT or AST) increases and hepatic tissue activity lesion, HBeAg are positive or negative with compensatory chronic liver disease
Do not receive the patient of nucleoside medicine treatment, and has the patient of tolerance to Lamivudine.Entecavir in 2005
The U.S. is approved to list, and the country listed so far includes 30 countries and the ground such as Canada, Britain, Germany, France, Australia
Area.The Entecavir tablet that Shanghai Shi Guibao pharmaceutical Co. Ltds of Sino-U.S.'s in November, 2005 declare is approved in Chinese localized production.
The product specification is 0.5mg.Usage and dosage：Adult and 16 years old or more teenager take orally this product, once a day, each 0.5mg.
Viremia virusemia occurs when lamivudine therapy or the patient of lamivudine resistant mutations occurs to be each 1mg once a day.The product
It should be administered at empty stomach (before the meal or at least 2 hours postprandial).The country has had listed entecavir dispersible tablet and capsule, specification 0.5mg
And 1.0mg, indication are identical as Yuan Yan enterprises.
CN102552210A provides a kind of entecavir capsule, including Entecavir, pregelatinized starch and microcrystalline cellulose
Element, in vitro have dissolved corrosion similar with former triturate Entecavir tablet, in human body with former triturate Entecavir tablet
Bioequivalence.
It includes entecavir that CN105001223A, which discloses a kind of Entecavir crystalline compounds and its capsule preparations, component,
Wei crystalline compounds, solubilizer, filler, disintegrant, lubricant, adhesive etc..
CN103432098A discloses a kind of Entecavir capsule, is made in capsule shells by Contents Fill, described interior
Tolerant is to obtain drug containing fine powder and lubricant mixing, and the drug containing fine powder is by Entecavir, meglumine and water soluble bulk
Agent is spray-dried after being dissolved in the water.
CN103110608A discloses a kind of entecavir capsule, by encapsulated shell after dry particl and talcum powder mixing
At the dry particl is prepared as follows：Entecavir and solid dispersion carrier are dissolved in absolute ethyl alcohol, then added
Enter the disintegrant insoluble in ethyl alcohol to be uniformly dispersed, be dried under reduced pressure and wave except absolute ethyl alcohol, obtains being attached to the disintegrant surface
Solid dispersions, it is dry then with filler and adhesive wet granulation.
CN102106856A provides a kind of entecavir medicinal composition, including Entecavir, adhesive, plasticizer and
Pharmaceutical acceptable carrier matrix, wherein Entecavir are adhered in pharmaceutical acceptable carrier matrix.
CN102008447A provides a kind of entecavir solid dispersion, mainly by Entecavir, carrier and spits
Temperature -80 is made, and the carrier is polyethylene glycol and/or poloxamer.
The Entikawei solid preparation listed at present both at home and abroad and the above-mentioned prior art still have following defect：(1) grace
Belong to the third class drug of Biopharmaceutics Classification system (BCS) for card Wei, oral drugs permeability is low, bioavilability
It is low；(2) there is food effect, for optimum curative effect (improving bioavilability), need to be administered at empty stomach, therefore there are patient compliances to ask
Topic；(3) supplementary product kind is more in prescription, preparation process is complicated, cost is higher.
Therefore, how to obtain that a kind of high bioavilability, high patient compliance and prescription be simple, entecavir of simple process
Wei oral preparation is this field urgent problem to be solved.
Inventor surprisingly has found in the studying for a long period of time of entecavir capsule pharmaceutical composition, by Entecavir raw material and
It is total to micro mist together after the mixing of magnesium stearate auxiliary material, then the entecavir capsule being mixed to prepare with pregelatinized starch, microcrystalline cellulose
Pharmaceutical composition, with higher bioavilability and not by food effect, so as to complete the present invention.
Invention content
The purpose of the present invention is to provide a kind of entecavir capsule pharmaceutical compositions and preparation method thereof, are by as follows
What technical solution was realized：
The present invention provides a kind of entecavir capsule pharmaceutical composition, and it includes micronizing Entecavir, micronizing are stearic
Sour magnesium, pregelatinized starch, microcrystalline cellulose.
Further, every 1000 capsules of the entecavir capsule pharmaceutical composition contain：It is micronized Entecavir 0.5g
(with C12H15N5O3Meter), it is micronized magnesium stearate 0.1-2g, pregelatinized starch 30-100g, microcrystalline cellulose 30-100g.
In one embodiment, the Size Distribution of the micronizing Entecavir is D90≤30μm。
In one embodiment, the Size Distribution of the micronizing magnesium stearate is D90≤30μm。
Further, the micronizing Entecavir and micronizing magnesium stearate are auxiliary by Entecavir raw material and magnesium stearate
Total micronizing is carried out after material mixing to be made.
In embodiments, the microcrystalline cellulose can be selected from microcrystalline cellulose PH102, microcrystalline cellulose PH302, micro-
Crystalline cellulose PH301, microcrystalline cellulose PHM06, microcrystalline cellulose PHM25, microcrystalline cellulose KG-801, microcrystalline cellulose KG-
802, one or more combinations in microcrystalline cellulose 101, microcrystalline cellulose 102 and microcrystalline cellulose 200.
In one embodiment, every 1000 capsules of the entecavir capsule pharmaceutical composition contain：It is micronized entecavir
Wei 0.5g is micronized magnesium stearate 1.0g, pregelatinized starch 50g, microcrystalline cellulose PH102 50g；Wherein it is micronized entecavir
Wei and micronizing magnesium stearate are made by carrying out total micronizing after Entecavir raw material and the mixing of magnesium stearate auxiliary material, particle diameter distribution
Feature is D90≤30μm。
The present invention also provides a kind of preparation methods of entecavir capsule pharmaceutical composition, it is characterised in that including following step
Suddenly：
(1) by Entecavir raw material and magnesium stearate auxiliary material with three-dimensional mixer after mixing, input air flow pulverizer
In carry out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total to micro mist mixture, spare；
(2) pregelatinized starch, microcrystalline cellulose are crossed to 80 mesh sieve respectively, it is spare；
(3) by Entecavir magnesium stearate is total to micro mist mixture made from step (1) and microcrystalline cellulose is passed using equivalent
Addition mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., 1. mixture is carried out 1 with the pregelatinized starch being sieved
Secondary equivalent is progressively increased mixing, and the screening of 80 mesh is crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., it is remaining microcrystalline cellulose, remaining pre-
Gelling starch puts into always 30 minutes mixed with 10 revs/min of speed in Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Entecavir capsule pharmaceutical composition of the present invention has the following advantages：
(1) oral administration biaavailability of Entecavir is significantly improved；
(2) performance of pharmaceutical activity effect is taken, without being administered at empty stomach, greatly before the meal or after the meal not by food effect
Improve compliance of the patient to entecavir capsule greatly.
(3) formula composition is simple, of low cost, simple process, it is easy to accomplish preparation of industrialization.
Since Entecavir belongs to slightly solubility, hypotonicity drug, with external method (such as dissolution determination) come
It is infeasible to evaluate its bioavilability, must be evaluated using in vivo method.The present invention is acquired after being administered using rat oral gavage
Blood sample carries out LC-MS/MS analyses to evaluate.Studies have shown that its bioavilability is obviously carried after Entecavir is micronized
Height, inventor make its particle diameter distribution reach D more it has surprisingly been found that Entecavir is micronized altogether together with magnesium stearate90≤30
μm, the bioavilability of entecavir capsule pharmaceutical composition of the present invention obtains significantly more promotion, works as magnesium stearate:Grace is replaced
Effect is the most notable when the weight ratio of card Wei is within the scope of 0.2-4；Inventor also found simultaneously, by being made after this total micronizing
Entecavir capsule pharmaceutical composition its active constituent there is higher uniformity of dosage units, this low contains for Entecavir is this
Uniformity of dosage units problem prepared by gauge lattice (0.5mg/) oral solid formulation provides a kind of preferable solution.
Specific implementation mode
For a better understanding of the present invention, below by through the invention embodiment and experimental data to the present invention and its it is excellent
Gesture is described in detail and illustrates, but these embodiments are not intended to restrict the invention.
Embodiment 1
Prescription：
Preparation method：
(1) by the Entecavir of recipe quantity, magnesium stearate input three-dimensional mixer Turbula, turned with 100 revs/min
Speed mixing 2 hours is subsequently placed in airslide disintegrating mill and carries out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total
Micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose are crossed to 80 mesh sieve respectively, it is spare；
(3) by Entecavir magnesium stearate is total to micro mist mixture made from step (1) and microcrystalline cellulose is passed using equivalent
Addition mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., 1. mixture is carried out 1 with the pregelatinized starch being sieved
Secondary equivalent is progressively increased mixing, and the screening of 80 mesh is crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., it is remaining microcrystalline cellulose, remaining pre-
Gelling starch puts into always 30 minutes mixed with 10 revs/min of speed in Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Embodiment 2
Prescription：
Preparation method：
(1) Entecavir of recipe quantity, magnesium stearate are micronized respectively with airslide disintegrating mill, make its particle diameter distribution
Reach D90It≤30 μm, then puts into three-dimensional mixer Turbula, is mixed 2 hours with 100 revs/min of rotating speeds, obtained grace is replaced
Card Wei magnesium stearate micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose PH301 are crossed to 80 mesh sieve respectively, it is spare；
(3) Entecavir magnesium stearate micro mist mixture made from step (1) and microcrystalline cellulose PH301 are used into equivalent
Method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved into
1 equivalent of row is progressively increased mixing, and the screening of 80 mesh is crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., remaining microcrystalline cellulose
It is always 30 minutes mixed with 10 revs/min of speed in PH301, remaining pregelatinized starch input Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Embodiment 3
Prescription：
Preparation method：
(1) by the Entecavir of recipe quantity, magnesium stearate input three-dimensional mixer Turbula, turned with 100 revs/min
Speed mixing 2 hours is subsequently placed in airslide disintegrating mill and carries out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total
Micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose PHM25 are crossed to 80 mesh sieve respectively, it is spare；
(3) Entecavir magnesium stearate made from step (1) is total to micro mist mixture and microcrystalline cellulose PHM25 uses etc.
Amount method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved
Carry out 1 equivalent to progressively increase mixing, the screening of 80 mesh crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., residue microcrystalline cellulose
It is always 30 minutes mixed with 10 revs/min of speed in PHM25, remaining pregelatinized starch input Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Embodiment 4
Prescription：
Preparation method：
(1) Entecavir of recipe quantity, magnesium stearate are micronized respectively with airslide disintegrating mill, make its particle diameter distribution
Reach D90It≤30 μm, then puts into three-dimensional mixer Turbula, is mixed 2 hours with 100 revs/min of rotating speeds, obtained grace is replaced
Card Wei magnesium stearate micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose KG-802 are crossed to 80 mesh sieve respectively, it is spare；
(3) use Entecavir magnesium stearate micro mist mixture made from step (1) and microcrystalline cellulose KG-802 etc.
Amount method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved
Carry out 1 equivalent to progressively increase mixing, the screening of 80 mesh crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., residue microcrystalline cellulose
It is always 30 minutes mixed with 10 revs/min of speed in KG-802, remaining pregelatinized starch input Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Embodiment 5
Prescription：
Preparation method：
(1) by the Entecavir of recipe quantity, magnesium stearate input three-dimensional mixer Turbula, turned with 100 revs/min
Speed mixing 2 hours is subsequently placed in airslide disintegrating mill and carries out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total
Micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose PH101 are crossed to 80 mesh sieve respectively, it is spare；
(3) Entecavir magnesium stearate made from step (1) is total to micro mist mixture and microcrystalline cellulose 101 uses equivalent
Method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved into
1 equivalent of row is progressively increased mixing, and the screening of 80 mesh is crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., remaining microcrystalline cellulose 101,
It is always 30 minutes mixed with 10 revs/min of speed in remaining pregelatinized starch input Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Embodiment 6
Prescription：
Preparation method：
(1) by the Entecavir of recipe quantity, magnesium stearate input three-dimensional mixer Turbula, turned with 100 revs/min
Speed mixing 2 hours is subsequently placed in airslide disintegrating mill and carries out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total
Micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose PH102, microcrystalline cellulose PH302 are crossed to 80 mesh sieve respectively, it is standby
With；
(3) Entecavir magnesium stearate made from step (1) is total to micro mist mixture and microcrystalline cellulose PH102 uses etc.
Amount method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved
Carry out 1 equivalent to progressively increase mixing, the screening of 80 mesh crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., residue microcrystalline cellulose
It is always mixed with 10 revs/min of speed in PH102, microcrystalline cellulose PH302, remaining pregelatinized starch input Mixers with Multi-direction Movement
30 minutes；
(4) capsule, packaging are filled to get finished product.
Embodiment 7
Prescription：
Preparation method：
(1) by the Entecavir of recipe quantity, magnesium stearate input three-dimensional mixer Turbula, turned with 100 revs/min
Speed mixing 2 hours is subsequently placed in airslide disintegrating mill and carries out total micronizing, D is made90≤ 30 μm of Entecavir magnesium stearate is total
Micro mist mixture, it is spare；
(2) recipe quantity pregelatinized starch, microcrystalline cellulose PH102, microcrystalline cellulose 101 are crossed to 80 mesh sieve respectively, it is spare；
(3) Entecavir magnesium stearate made from step (1) is total to micro mist mixture and microcrystalline cellulose PH102 uses etc.
Amount method of progressively increasing mixes 4 times, crosses 80 mesh sieve after mixing every time, obtains mixture 1., by mixture 1. with the pregelatinized starch that has been sieved
Carry out 1 equivalent to progressively increase mixing, the screening of 80 mesh crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., residue microcrystalline cellulose
In PH102, microcrystalline cellulose 101, remaining pregelatinized starch input Mixers with Multi-direction Movement 30 are always mixed with 10 revs/min of speed
Minute；
(4) capsule, packaging are filled to get finished product.
1 bioavilability comparative studies of test example
It has studied 1 product of the embodiment of the present invention and commercially available original and grinds product Entecavir tablet (Bo Luding), commercially available imitated
The bioavilability of product entecavir dispersible tablet (profit is many) compares.18 male Wistar rats are selected, the present invention is randomly divided into
The many groups of 1 sample sets of embodiment, Bo Luding groups, profit, every group each 6.Under whole normal water, meal situation, every group of rat with
The dosage gastric infusion Entecavir suspension (being dissolved in physiological saline) of 0.5mg/kg.And before administration and after administration
0.08, it samples within 0.17,0.33,0.5,1,2,4,8,12,24,36,48,60,72,84,96 hour, after sample treatment, uses
LC-MS/MS carries out the analysis detection of bioavilability.As a result as shown in table 1 below.
The many bioavilability animal test results of 1 product of the present invention of table, Bo Luding, profit
Upper table is analyzed it is found that the bioavilability (AUC) of 1 product of the embodiment of the present invention is improved than rich road stator
66.7%, dispersible tablets more than profit improve 61.2%；Half-life period (t1/2) to extend 7~8 small for more than rich road stator and profit dispersible tablets
When.Test result shows that product of the present invention improves treatment in the case that non-fasting compared with rich road stator and many dispersible tablets of profit
Effect, effectively overcomes the problem of existing product must be administered at empty stomach, improves compliance of the patient to drug.
Test example 2 dissolves out homogeneity comparative studies
Due to Entecavir oral solid formulation specification 0.5mg/, belong to low content specification, is referred to using dissolution homogeneity
Mark is more suitable to investigate its uniformity of dosage units.
Inventor grinds product Entecavir tablet (Bo Luding), commercially available Counterfeit Item grace to 1 product of embodiment and commercially available original
Dissolution homogeneity for card Wei dispersible tablet (profit many) is studied, they three kinds of different dissolution mediums (pH2.0, pH6.8's
Phosphate buffer and water) in different time points dissolution uniformity (dissolution rate relative standard deviation RSD, %) result such as following table
(basket method, 900mL media, 100 revs/min, n=12) shown in 2：
The many dissolution uniformities (dissolution rate relative standard deviation RSD, %) of 2 product of the present invention of table, Bo Luding, profit
As can be seen from the above table, 1 product of the embodiment of the present invention is in three kinds of different dissolution mediums, molten at variant time point
Out-degree relative standard deviation RSD is substantially less than commercially available rich road stator and many dispersible tablets of profit, shows the Entecavir of the present invention
Tablet medicament composition has more uniform uniformity of dosage units and more stable dissolution release.
Claims (8)
1. a kind of entecavir capsule pharmaceutical composition, which is characterized in that described pharmaceutical composition include micronizing Entecavir,
It is micronized magnesium stearate, pregelatinized starch, microcrystalline cellulose.
2. entecavir capsule pharmaceutical composition according to claim 1, which is characterized in that every 1000 capsules contain：
3. entecavir capsule pharmaceutical composition according to claim 1 or 2, it is characterised in that：The micronizing grace is replaced
The Size Distribution of card Wei is D90≤30μm。
4. entecavir capsule pharmaceutical composition according to claim 1 or 2, it is characterised in that：The micronizing is stearic
The Size Distribution of sour magnesium is D90≤30μm。
5. according to claim 1-4 any one of them entecavir capsule pharmaceutical compositions, it is characterised in that：The micronizing
Entecavir and micronizing magnesium stearate are made by carrying out total micronizing after Entecavir raw material and the mixing of magnesium stearate auxiliary material.
6. according to claim 1-5 any one of them entecavir capsule pharmaceutical compositions, it is characterised in that the crystallite is fine
Dimension element is selected from microcrystalline cellulose PH102, microcrystalline cellulose PH302, microcrystalline cellulose PH301, microcrystalline cellulose PHM06, crystallite
Cellulose PHM25, microcrystalline cellulose KG-801, microcrystalline cellulose KG-802, microcrystalline cellulose 101, microcrystalline cellulose 102 and micro-
One or more combinations in crystalline cellulose 200.
7. a kind of entecavir capsule pharmaceutical composition, it is characterised in that every 1000 capsules contain：It is micronized Entecavir 0.5g
(with C12H15N5O3Meter), it is micronized magnesium stearate 1.0g, pregelatinized starch 50g, microcrystalline cellulose PH102 50g, the micro mist
It is D to change Entecavir and micronizing magnesium stearate Size Distribution90It is≤30 μm, auxiliary by Entecavir raw material and magnesium stearate
Total micronizing is carried out after material mixing to be made.
8. the preparation method of claim 1-7 any one of them entecavir capsule pharmaceutical compositions, it is characterised in that including
Following steps：
(1) by Entecavir raw material and magnesium stearate auxiliary material with three-dimensional mixer after mixing, in input air flow pulverizer into
Row micronizing altogether, is made D90≤ 30 μm of Entecavir magnesium stearate is total to micro mist mixture, spare；
(2) pregelatinized starch, microcrystalline cellulose are crossed to 80 mesh sieve respectively, it is spare；
(3) Entecavir magnesium stearate made from step (1) is total to micro mist mixture and microcrystalline cellulose uses equivalent gradually-increased
Mixing 4 times crosses 80 mesh sieve, obtains mixture 1. every time after mixing, 1. mixture with the pregelatinized starch that has been sieved is carried out 1 inferior
Amount is progressively increased mixing, and the screening of 80 mesh is crossed after mixing and is dissipated, obtains mixture 2., by mixture 2., remaining microcrystalline cellulose, residue pregelatinated
Starch puts into always 30 minutes mixed with 10 revs/min of speed in Mixers with Multi-direction Movement；
(4) capsule, packaging are filled to get finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811079954.0A CN108785273B (en) | 2018-09-18 | 2018-09-18 | Entecavir capsule pharmaceutical composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811079954.0A CN108785273B (en) | 2018-09-18 | 2018-09-18 | Entecavir capsule pharmaceutical composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108785273A true CN108785273A (en) | 2018-11-13 |
| CN108785273B CN108785273B (en) | 2021-01-01 |
Family
ID=64082048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811079954.0A Active CN108785273B (en) | 2018-09-18 | 2018-09-18 | Entecavir capsule pharmaceutical composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108785273B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101325945A (en) * | 2005-12-12 | 2008-12-17 | 雅戈泰克股份公司 | Powder compositions for inhalation |
| WO2011076412A1 (en) * | 2009-12-23 | 2011-06-30 | Ratiopharm Gmbh | Oral form of administration comprising entecavir |
| CN102552210A (en) * | 2012-01-10 | 2012-07-11 | 四川海思科制药有限公司 | Entecavir capsule and preparation method thereof |
| CN103435614A (en) * | 2013-08-23 | 2013-12-11 | 四川海思科制药有限公司 | Entecavir compound |
-
2018
- 2018-09-18 CN CN201811079954.0A patent/CN108785273B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101325945A (en) * | 2005-12-12 | 2008-12-17 | 雅戈泰克股份公司 | Powder compositions for inhalation |
| WO2011076412A1 (en) * | 2009-12-23 | 2011-06-30 | Ratiopharm Gmbh | Oral form of administration comprising entecavir |
| CN102552210A (en) * | 2012-01-10 | 2012-07-11 | 四川海思科制药有限公司 | Entecavir capsule and preparation method thereof |
| CN103435614A (en) * | 2013-08-23 | 2013-12-11 | 四川海思科制药有限公司 | Entecavir compound |
Non-Patent Citations (1)
| Title |
|---|
| 叶勇等: "《制药工艺学》", 28 February 2014, 华南理工大学出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108785273B (en) | 2021-01-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sahoo et al. | Fast Dissolving Tablet: As a potential drug delivery system | |
| CN102988296A (en) | Celecoxib solid dispersion and preparation method thereof | |
| HUE035241T2 (en) | Darunavir combination formulations | |
| CN103006661A (en) | Preparation containing lurasidone hydrochloride and preparation method thereof | |
| KR101562608B1 (en) | Compound chemical medicine acting on respiratory disease, preparation process and use thereof | |
| CN112585192A (en) | Cellulose powder, use thereof and tablet | |
| CN104940152A (en) | Pharmaceutical composition containing solifenacin succinate | |
| CN106074423A (en) | Diabecron sustained-release tablet agent and preparation method thereof | |
| TWI724534B (en) | Cellulose powder, lozenges and methods for manufacturing lozenges | |
| JP2017502941A (en) | Pharmaceutical dosage form | |
| CN106309395A (en) | Tacrolimus sustained-release tablets and preparation method thereof | |
| CN106880611A (en) | A kind of tolvaptan preparation of tolvaptan and water soluble adjuvant containing micronizing | |
| CN114146089B (en) | Pharmaceutical composition containing efavirenz, tenofovir and emtricitabine | |
| CN108785273B (en) | Entecavir capsule pharmaceutical composition and preparation method thereof | |
| CN103284953B (en) | Bicyclol solid preparation and preparation method thereof | |
| CN108186590A (en) | Huperzine slow-release orally disintegrating tablets and preparation method thereof | |
| CN103768071B (en) | A kind of oral formulations treating diabetes | |
| CN110960501B (en) | Norfloxacin capsule and preparation method thereof | |
| EP3345626A1 (en) | Super-rapid disintegrating tablet, and method for producing same | |
| CN102525967B (en) | Entecavir oral solid composition and preparation method thereof | |
| CN106214646A (en) | A kind of silybin meglumine preparation | |
| CN107375225B (en) | Level release formulation of a kind of succinic acid furan Luo Qu and preparation method thereof | |
| CN101244068B (en) | Hemsleyadin sustained-release preparation | |
| CN110917170A (en) | Candesartan cilexetil-containing capsule preparation and preparation method thereof | |
| CN104337783B (en) | A kind of capecitabine tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |