CN109700774A - A kind of perindopril tert-butylamine piece and its powder vertical compression technique - Google Patents
A kind of perindopril tert-butylamine piece and its powder vertical compression technique Download PDFInfo
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- CN109700774A CN109700774A CN201910163592.1A CN201910163592A CN109700774A CN 109700774 A CN109700774 A CN 109700774A CN 201910163592 A CN201910163592 A CN 201910163592A CN 109700774 A CN109700774 A CN 109700774A
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- butylamine
- powder
- perindopril tert
- compression technique
- vertical compression
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Abstract
The invention discloses a kind of powder vertical compression technique of perindopril tert-butylamine piece, every 1000 contain the component of following weight: 2g~8g perindopril tert-butylamine, 20g~66g lactose, 20g~66g microcrystalline cellulose, 0.09~0.45g colloidal silicon dioxide and 0.27g~0.9g magnesium stearate.The present invention can delay the disintegration of perindopril tert-butylamine piece by adjusting the incorporation time and control hardness of magnesium stearate, dissolution curve adjusted can grind product with original and be consistent, diindyl is trained in the placement process of stability, humidity and temperature will affect the stability of product, storage temperature is 30 DEG C or less preservations, but humidity needs packaging material to go to obstruct, this product is using PVC+ aluminium foil as interior packaging material, interior plus desiccant, outer packaging material selection aluminum layer thickness are more than that 20 μm of compound membrane bags can be effectively ensured product and not be affected by humidity.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of perindopril tert-butylamine piece and its powder vertical compression technique.
Background technique
The specification of perindopril tert-butylamine piece list marketing is 2mg, 4mg and 8mg, since specification is small, and is limited to raw material
The influence of self property, so will appear underproof situation often when preparing using powder vertical compression technique.
The Yuan Yan company of perindopril tert-butylamine be French servier, announce product description, prescription at
It is divided into 2mg containing perindopril tert-butylamine, 4mg or 8mg, lactose, microcrystalline cellulose, colloidal silicon dioxide and magnesium stearate.
The prescription that 2005/094793 A1 of patent WO discloses perindopril tert-butylamine piece matches four examples, wherein having
Two prescription proportions are similar, are principal component 4mg/ piece, lactose 62.78mg/ piece, microcrystalline cellulose 22.50mg/ piece, colloidal state two
Silica 0.27mg/ piece, magnesium stearate 0.45mg/ piece are not uniquely all microcrystalline cellulose, indicate in a copy of it proportion micro-
The water content of crystalline cellulose answers < 1.5%, in addition a not require.The range of colloidal silicon dioxide is mentioned in claim
0.1%~0.9%, optimal 0.50%~0.83%, magnesium stearate 0.3%~5.0%, optimal 0.3%~1.5% this patent is also
The hybrid mode for disclosing supplementary material is dry mixed.
Patent CN104586800 discloses the composition range of perindopril tert-butylamine piece and the technique of direct powder compression.
Claim prescription be 1~3 part of Perindopril, 60~75 parts of lactose, 17~25 parts of microcrystalline cellulose, magnesium stearate 0.3~0.8
Part, 0.3~0.9 part of silica, claim technique is 1) to take perindopril tert-butylamine salt, is mixed with microcrystalline cellulose, mistake
Sieve mixes；2) it is mixed again with portion of Lactose；3) above-mentioned mixed powder and remaining lactose, silica are mixed；4) it is eventually adding hard
Fatty acid magnesium mixing, sample detection, tabletting；5) aluminium-plastic bubble plate packing is used, built-in desiccant is cladded with compound membrane bag；State step (1)
The sieve mesh of middle sieving is -100 mesh of 80 mesh；Aluminium-plastic bubble plate packing in above-mentioned steps (5), specifically: PVC+ aluminium foil；Above-mentioned steps
(5) desiccant is silica gel or molecular sieve in.
Summary of the invention
Goal of the invention: in order to solve the deficiencies in the prior art, the present invention provides a kind of perindopril tert-butylamine piece and its
Powder vertical compression technique.
Technical solution: a kind of perindopril tert-butylamine piece, every 1000 components containing weight once: it is general that 2g~8g trains diindyl
Sharp tert-butylamine, 20g~66g lactose, 20g~66g microcrystalline cellulose, 0.09g~0.45g colloidal silicon dioxide and 0.27g~
0.9g magnesium stearate.
A kind of powder vertical compression technique of the perindopril tert-butylamine piece, includes the following steps:
Step a. raw material is uniformly mixed with colloidal silicon dioxide, obtains powder 1；
Step b. powder 1 progressively increases with lactose equivalent to be mixed, and sieving obtains powder 2；
Step c. powder 2 is mixed with remaining lactose and microcrystalline cellulose, obtains powder 3；
Step d. powder 3 is mixed with magnesium stearate, sample detection, tabletting；
Step e. uses aluminium-plastic bubble plate packing, built-in desiccant, outsourcing compound membrane bag.
As optimization: in the step c, crossing grit number is 40 mesh.
As optimization: in the step c, the moisture of microcrystalline cellulose should be less than 1.5%.
As optimization: in the step d, the incorporation time of powder 3 and magnesium stearate answers > 20min.
As optimization: in the step d, the hardness of tablet is 4.5~8kg.
As optimization: in the step d, the hardness of tablet is preferably 5.5kg~6.5kg.
As optimization: in the step e, aluminum-plastic blister is PVC+ aluminium foil.
As optimization: in the step e, desiccant is silica gel, 20 μm of compound membrane bag aluminum layer thickness >.
As optimization: the partial size for controlling raw material is D90=10 μm~50 μm.
The utility model has the advantages that the present invention can make the granule content of all batches by control partial size and the crucial hybrid technique of adjustment
The uniformity is held in 4% or less (standard 5%)；Perindopril tert-butylamine belongs to BCS three classes drug, and height dissolves hyposmosis,
Half-life short, in order to improve bioavailability, after perindopril tert-butylamine piece enters in vivo, disintegration rate is unsuitable too fast.Pass through
The incorporation time and control hardness that adjust magnesium stearate can delay the disintegration of perindopril tert-butylamine piece, and dissolution adjusted is bent
Line can grind product with original and be consistent, and train diindyl in the placement process of stability, humidity and temperature will affect the steady of product
Qualitative, storage temperature is 30 DEG C or less preservations, but humidity needs packaging material to go to obstruct, and this product uses PVC+ aluminium foil as interior packaging material,
Interior plus desiccant, outer packaging material selection aluminum layer thickness are more than that 20 μm of compound membrane bags can be effectively ensured product and not be affected by humidity.
In the present invention, (1) lactose plays diluent in prescription, and the ratio of lactose and crystallite has the mobility of powder
Certain influence, but dissolved corrosion is not influenced.(2) colloidal silicon dioxide plays glidant in prescription, reasonable
In amount ranges, the height of dosage will not influence dissolved corrosion.(3) effect of magnesium stearate super fatting agent in prescription, but use
Amount and incorporation time will affect the dissolved corrosion of tablet.(4) partial size of raw material will affect the uniformity of dosage units of particle.(5) raw material
With the uniformity of dosage units for also influencing whether particle of different auxiliary material.(6) thickness of compound membrane bag aluminium layer will affect the stabilization of product
Property.
Specific embodiment
The technical scheme in the embodiments of the invention will be clearly and completely described below, so that the technology of this field
Personnel can better understand advantages and features of the invention, to make apparent boundary to protection scope of the present invention
It is fixed.Embodiment described in the invention is only a part of the embodiment of the present invention, instead of all the embodiments, based on the present invention
In embodiment, those of ordinary skill in the art's every other implementation obtained without making creative work
Example, shall fall within the protection scope of the present invention.
Embodiment
A kind of perindopril tert-butylamine piece, every 1000 components containing weight once: 2g~8g perindopril tert-butylamine,
20g~66g lactose, 20g~66g microcrystalline cellulose, 0.09~0.45g colloidal silicon dioxide and 0.27g~0.9g magnesium stearate.
A kind of powder vertical compression technique of the perindopril tert-butylamine piece, includes the following steps:
Step a. raw material is uniformly mixed with colloidal silicon dioxide, obtains powder 1；
Step b. powder 1 progressively increases with lactose equivalent to be mixed, and sieving obtains powder 2；
Step c. powder 2 is mixed with remaining lactose and microcrystalline cellulose, obtains powder 3；
Step d. powder 3 is mixed with magnesium stearate, sample detection, tabletting；
Step e. uses aluminium-plastic bubble plate packing, built-in desiccant, outsourcing compound membrane bag.
In the present embodiment, in the step c, crossing grit number is 40 mesh.The moisture of microcrystalline cellulose should be less than 1.5%.
In the step d, the incorporation time of powder 3 and magnesium stearate answers > 20min.The hardness of tablet is 4.5~8kg.Tablet
Hardness is 5.5kg~6.5kg.In the step e, aluminum-plastic blister is PVC+ aluminium foil.Desiccant is silica gel, compound membrane bag aluminium layer
20 μm of thickness G T.GT.GT.The partial size for controlling raw material is D90=10 μm~50 μm.
Comparative example 1
1 comparative example 1 of table at being grouped as table
| Ingredient | Dosage |
| Perindopril tert-butylamine | 2 |
| Lactose | 65.73 |
| Microcrystalline cellulose | 21.91 |
| Colloidal silicon dioxide | 0.09 |
| Magnesium stearate | 0.27 |
| Total amount | 90 |
The preparation method comprises the following steps: taking recipe quantity perindopril tert-butylamine, it is uniformly mixed with colloidal silicon dioxide, obtains powder 1.By powder
The lactose of end 1 and equivalent sequentially adds hopper mixing machine, and setting speed 20rpm mixes 5min, obtains powder 2.Add into mixing machine
Enter the lactose with 2 equivalent of powder, setting speed 20rpm mixes 5min, obtains powder 3.Powder 3 crosses 40 meshes, obtains powder 4.It will
The microcrystalline cellulose of powder 4, remaining lactose and recipe quantity sequentially adds hopper mixing machine, setting speed 20rpm, mixing
20min obtains powder 5.Hopper mixing machine is added in the magnesium stearate of recipe quantity, setting speed 20rpm mixes 20min, sampling inspection
It surveys, tabletting.
Comparative example 2
2 comparative example 2 of table at being grouped as table
| Ingredient | Dosage |
| Perindopril tert-butylamine | 4 |
| Lactose | 42.33 |
| Microcrystalline cellulose | 42.32 |
| Colloidal silicon dioxide | 0.45 |
| Magnesium stearate | 0.9 |
| Total amount | 90 |
The preparation method comprises the following steps: taking recipe quantity perindopril tert-butylamine, it is uniformly mixed with colloidal silicon dioxide, obtains powder 1.By powder
The lactose of end 1 and equivalent sequentially adds hopper mixing machine, and setting speed 20rpm mixes 5min, obtains powder 2.Add into mixing machine
Enter the lactose with 2 equivalent of powder, setting speed 20rpm mixes 5min, obtains powder 3.Powder 3 crosses 40 meshes, obtains powder 4.It will
The microcrystalline cellulose of powder 4, remaining lactose and recipe quantity sequentially adds hopper mixing machine, setting speed 20rpm, mixing
20min obtains powder 5.Hopper mixing machine is added in the magnesium stearate of recipe quantity, setting speed 20rpm mixes 20min, sampling inspection
It surveys, tabletting.
Comparative example 3
3 comparative example 3 of table at being grouped as table
The preparation method comprises the following steps: taking recipe quantity perindopril tert-butylamine, it is uniformly mixed with colloidal silicon dioxide, obtains powder 1.By powder
The lactose of end 1 and equivalent sequentially adds hopper mixing machine, and setting speed 20rpm mixes 5min, obtains powder 2.Add into mixing machine
Enter the lactose with 2 equivalent of powder, setting speed 20rpm mixes 5min, obtains powder 3.Powder 3 crosses 40 meshes, obtains powder 4.It will
The microcrystalline cellulose of powder 4, remaining lactose and recipe quantity sequentially adds hopper mixing machine, setting speed 20rpm, mixing
20min obtains powder 5.Hopper mixing machine is added in the magnesium stearate of recipe quantity, setting speed 20rpm mixes 20min, sampling inspection
It surveys, tabletting.
The present invention is by control partial size and adjusting crucial hybrid technique can make the granule content uniformity of all batches equal
It is maintained at 4% or less (standard 5%)；Perindopril tert-butylamine belongs to BCS three classes drug, height dissolution hyposmosis, half-life short,
In order to improve bioavailability, after perindopril tert-butylamine piece enters in vivo, disintegration rate is unsuitable too fast.By adjusting stearic acid
The incorporation time of magnesium and control hardness can delay the disintegration of perindopril tert-butylamine piece, dissolution curve adjusted can and it is former
It grinds product to be consistent, for perindopril tert-butylamine in the placement process of stability, humidity and temperature will affect the steady of product
Qualitative, storage temperature is 30 DEG C or less preservations, but humidity needs packaging material to go to obstruct, and this product uses PVC+ aluminium foil as interior packaging material,
Interior plus desiccant, outer packaging material selection aluminum layer thickness are more than that 20 μm of compound membrane bags can be effectively ensured product and not be affected by humidity.
In the present invention, (1) lactose plays diluent in prescription, and the ratio of lactose and crystallite has the mobility of powder
Certain influence, but dissolved corrosion is not influenced.(2) colloidal silicon dioxide plays glidant in prescription, reasonable
In amount ranges, the height of dosage will not influence dissolved corrosion.(3) effect of magnesium stearate super fatting agent in prescription, but use
Amount and incorporation time will affect the dissolved corrosion of tablet.(4) partial size of raw material will affect the uniformity of dosage units of particle.(5) raw material
The uniformity of dosage units for also influencing whether particle is mixed with different auxiliary material.(6) thickness of compound membrane bag aluminium layer will affect the steady of product
It is qualitative.
Claims (9)
1. a kind of perindopril tert-butylamine piece, it is characterised in that: every 1000 contain the component of following weight: it is general that 2g~8g trains diindyl
Sharp tert-butylamine, 20g~66g lactose, 20g~66g microcrystalline cellulose, 0.09g~0.45g colloidal silicon dioxide and 0.27g~
0.9g magnesium stearate.
2. a kind of powder vertical compression technique of perindopril tert-butylamine piece according to claim 1, it is characterised in that: including such as
Lower step:
Step a. raw material is uniformly mixed with colloidal silicon dioxide, obtains powder 1；
Step b. powder 1 progressively increases with lactose equivalent to be mixed, and sieving obtains powder 2；
Step c. powder 2 is mixed with remaining lactose and microcrystalline cellulose, obtains powder 3；
Step d. powder 3 is mixed with magnesium stearate, sample detection, tabletting；
Step e. uses aluminium-plastic bubble plate packing, built-in desiccant, outsourcing compound membrane bag.
3. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In b, crossing grit number is 40 mesh.
4. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In c, the moisture of microcrystalline cellulose should be less than 1.5%.
5. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In d, the incorporation time of powder 3 and magnesium stearate answers > 20min.
6. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In d, the hardness of tablet is 4.5~8kg, preferably 5.5kg~6.5kg.
7. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In e, aluminum-plastic blister is PVC+ aluminium foil.
8. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: the step
In e, desiccant is silica gel, 20 μm of compound membrane bag aluminum layer thickness >.
9. the powder vertical compression technique of perindopril tert-butylamine piece according to claim 2, it is characterised in that: control raw material
Partial size is D90=10 μm~50 μm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910163592.1A CN109700774A (en) | 2019-03-05 | 2019-03-05 | A kind of perindopril tert-butylamine piece and its powder vertical compression technique |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910163592.1A CN109700774A (en) | 2019-03-05 | 2019-03-05 | A kind of perindopril tert-butylamine piece and its powder vertical compression technique |
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| Publication Number | Publication Date |
|---|---|
| CN109700774A true CN109700774A (en) | 2019-05-03 |
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|---|---|---|---|
| CN201910163592.1A Pending CN109700774A (en) | 2019-03-05 | 2019-03-05 | A kind of perindopril tert-butylamine piece and its powder vertical compression technique |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005094793A1 (en) * | 2004-03-29 | 2005-10-13 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Process for preparing a solid pharmaceutical composition |
| WO2008125134A1 (en) * | 2007-04-13 | 2008-10-23 | Helm Ag | Process for the preparation of perindopril-tert-butylamine adsorbates |
| CN104434869A (en) * | 2014-10-25 | 2015-03-25 | 广东新峰药业股份有限公司 | Cefdinir capsule and preparation method thereof |
| CN104586800A (en) * | 2015-01-27 | 2015-05-06 | 江苏嘉逸医药有限公司 | Perindopril tablets and direct tabletting process of perindopril tablet powder |
| CN105395497A (en) * | 2015-12-04 | 2016-03-16 | 杭州新诺华医药有限公司 | Stable alpha-crystalline form perindopril tert-butylamine tablet and preparation method thereof |
| CN106074427A (en) * | 2016-07-31 | 2016-11-09 | 合肥远志医药科技开发有限公司 | A kind of maleic acid Afatinib tablet and preparation method thereof |
-
2019
- 2019-03-05 CN CN201910163592.1A patent/CN109700774A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005094793A1 (en) * | 2004-03-29 | 2005-10-13 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Process for preparing a solid pharmaceutical composition |
| WO2008125134A1 (en) * | 2007-04-13 | 2008-10-23 | Helm Ag | Process for the preparation of perindopril-tert-butylamine adsorbates |
| CN104434869A (en) * | 2014-10-25 | 2015-03-25 | 广东新峰药业股份有限公司 | Cefdinir capsule and preparation method thereof |
| CN104586800A (en) * | 2015-01-27 | 2015-05-06 | 江苏嘉逸医药有限公司 | Perindopril tablets and direct tabletting process of perindopril tablet powder |
| CN105395497A (en) * | 2015-12-04 | 2016-03-16 | 杭州新诺华医药有限公司 | Stable alpha-crystalline form perindopril tert-butylamine tablet and preparation method thereof |
| CN106074427A (en) * | 2016-07-31 | 2016-11-09 | 合肥远志医药科技开发有限公司 | A kind of maleic acid Afatinib tablet and preparation method thereof |
Non-Patent Citations (3)
| Title |
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| 张宗强: "粉末直接压片对辅料的应用要求探讨", 《海峡药学》 * |
| 王涛: "硬脂酸镁在直接压片工艺中产生的软化效应", 《药学实践杂志》 * |
| 范青生主编: "《保健食品工艺学》", 30 November 2006, 中国医药科技出版社 * |
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| SE01 | Entry into force of request for substantive examination | ||
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Application publication date: 20190503 |