CN105343026B - Escitalopram oxalate effervescent tablet formula and preparation process - Google Patents
Escitalopram oxalate effervescent tablet formula and preparation process Download PDFInfo
- Publication number
- CN105343026B CN105343026B CN201510732767.8A CN201510732767A CN105343026B CN 105343026 B CN105343026 B CN 105343026B CN 201510732767 A CN201510732767 A CN 201510732767A CN 105343026 B CN105343026 B CN 105343026B
- Authority
- CN
- China
- Prior art keywords
- parts
- pvpk
- mesh
- escitalopram oxalate
- sucrose
- 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.)
- Active
Links
- KTGRHKOEFSJQNS-BDQAORGHSA-N (1s)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 KTGRHKOEFSJQNS-BDQAORGHSA-N 0.000 title claims abstract description 59
- 229960005086 escitalopram oxalate Drugs 0.000 title claims abstract description 59
- 239000007938 effervescent tablet Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 238000009472 formulation Methods 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 108
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 72
- 239000002245 particle Substances 0.000 claims description 44
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 40
- 235000005135 Micromeria juliana Nutrition 0.000 claims description 36
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 36
- 241000246354 Satureja Species 0.000 claims description 36
- 235000007315 Satureja hortensis Nutrition 0.000 claims description 36
- 229930006000 Sucrose Natural products 0.000 claims description 36
- 229960004543 anhydrous citric acid Drugs 0.000 claims description 36
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 36
- 239000005720 sucrose Substances 0.000 claims description 36
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 34
- 108010011485 Aspartame Proteins 0.000 claims description 27
- 239000000605 aspartame Substances 0.000 claims description 27
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 27
- 229960003438 aspartame Drugs 0.000 claims description 27
- 235000010357 aspartame Nutrition 0.000 claims description 27
- 206010013786 Dry skin Diseases 0.000 claims description 22
- 238000001035 drying Methods 0.000 claims description 22
- 238000005469 granulation Methods 0.000 claims description 22
- 230000003179 granulation Effects 0.000 claims description 22
- 239000008188 pellet Substances 0.000 claims description 22
- 239000011122 softwood Substances 0.000 claims description 21
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 20
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 16
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 12
- 239000007932 molded tablet Substances 0.000 claims description 11
- 229960004793 sucrose Drugs 0.000 claims description 11
- 235000006408 oxalic acid Nutrition 0.000 claims description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- 229960004341 escitalopram Drugs 0.000 claims 2
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 abstract description 26
- 239000007884 disintegrant Substances 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 5
- 239000002075 main ingredient Substances 0.000 abstract description 5
- 239000002253 acid Substances 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 208000019906 panic disease Diseases 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 49
- 238000005303 weighing Methods 0.000 description 16
- 238000004090 dissolution Methods 0.000 description 12
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 238000007873 sieving Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000008351 acetate buffer Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- 125000000185 sucrose group Chemical group 0.000 description 2
- 235000010894 Artemisia argyi Nutrition 0.000 description 1
- 240000004307 Citrus medica Species 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 244000030166 artemisia Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 239000003232 water-soluble binding agent Substances 0.000 description 1
Abstract
The invention belongs to medicine preparation technology scope, main ingredient escitalopram oxalate is suitable for treatment depression, treats the panic disorder with or without agoraphobe.Escitalopram oxalate effervescent tablet uses the tablet forming technique pelletized respectively by the compositing formulas such as main ingredient, disintegrant and aromatic, acid disintegrant and alkaline disintegrant.Using this formula and technique are easily operated, product quality is controllable, take good mouthfeel, at low cost.
Description
Technical field
The invention belongs to medicine preparation technology scopes, and in particular to the formula to escitalopram oxalate effervescent tablet and preparation
Technique.
Background technology
Escitalopram oxalate is clinically used for the treatment of major depressive disorder and generalized anxiety disorder.It belongs to selectively
Inhibit the selective serotonin reuptake inhibitor class in the serotonin reuptake transporter to nerve cell from synaptic cleft
(SSRI).Escitalopram oxalate reabsorbs the inhibiting effect with high selectivity to serotonin (5-HT), to going first
The re-absorption of adrenaline and dopamine influences very little.It improves nerve synapse by preventing serotonin (5-HT) from reabsorbing
The concentration of serotonin (5-HT) in gap, to generate antidepressant effect.Currently, the publication of escitalopram oxalate
Mainly there are conventional tablet, escitalopram oxalate piece at home and abroad to list already with clinical application preparation, with other dosage form phases
Than having the characteristics that character is stable, the conventional tablet accurate, of low cost, be easy to carry about with one, but listed of dosage is tired for swallowing
Difficult and depressed class patient's poor compliance, bioavilability are also influenced by dissolution rate.
Invention content
The present invention provides a kind of formula and preparation process of escitalopram oxalate effervescent tablet to solve Problems Existing,
Other auxiliary materials are added using escitalopram oxalate as primary raw material in the drug, and effervescent tablet is made, and facilitate swallow tablet to have tired
Difficult patient uses.
Escitalopram oxalate effervescent tablet, component are calculated as by weight：1-10 parts of escitalopram oxalate, it is acid
Disintegrant is selected from 13-23 parts of anhydrous citric acid, and alkaline disintegrant is selected from 25-35 parts of sodium bicarbonate, and sweetener is selected from sucrose 22-32
Part, aromatic is selected from savory 1-11 parts of the essence of orange, and sweetener is selected from 4-14 parts of aspartame, and lubricant is selected from polyethylene glycol-6000
3-13 parts, adhesive is selected from PVPK300.05-0.15 parts.
To optimize above-mentioned technical proposal, its component of the effervescent tablet is calculated as by weight：Escitalopram oxalate is
3.34 parts, 17.75 parts of anhydrous citric acid, 29.75 parts of sodium bicarbonate, 26.62 parts of sucrose, savory smart 5.74 parts of orange, aspartame
8.87 parts, 7.83 parts of polyethylene glycol-6000, PVPK300.1 part.
Its preparation process is specific as follows：
(1) it pre-processes：
By above-mentioned prescription by escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, the savory smart 80 mesh powder of orange
Broken, aspartame, polyethylene glycol-6000 cross 80 mesh sieve, spare；
(2) it pelletizes：
By the escitalopram oxalate pre-processed, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed, adds
Enter the PVPK of gross mass 38%30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of ± 5 DEG C of dryings, until pellet moisture≤
1.0%, 18 mesh sieves obtain particle a；
It by the sodium bicarbonate pre-processed, sucrose, is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system are soft
Material, the sieve granulation of 20 mesh, 40 DEG C of ± 5 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b.
(3) total mixed：
The polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
(4) tabletting：
Select the flat molded tablets in a state of excitement of Ф 8mm.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol water for being 50% with volume fraction is matched
The PVPK that mass fraction is 5% is made30Ethanol solution.
In order to ensure stability and the safety of product, the program of Consult drug research and development, it is compatible that We conducted supplementary materials
Property experiment, specific content of the test and result see the table below 1：
Table 1：Supplementary material compatibility test result
By that can be obtained with 1 test result of upper table, escitalopram oxalate and the mixture with each auxiliary material, high temperature,
After being placed 10 days under high humidity and illumination condition, compared with 0 day, related substance, character do not change, and illustrate that each auxiliary material ends with oxalic acid
It is good to take charge of Citalopram compatibility.
The escitalopram oxalate is the main ingredient of effervescent tablet, is main active, preferably above-mentioned by testing
Effervescent tablet, which is made, in amount ranges has more preferable curative effect；The acid disintegrant and alkaline disintegrant are respectively selected from anhydrous citron
Anhydrous citric acid and sodium bicarbonate is preferably used as disintegrant by a large number of experiments in acid, sodium bicarbonate, they live with main
Property ingredient escitalopram oxalate is used in compounding, and can effectively improve the activity of main ingredient, small to the harmful effect of drug-eluting,
On other preparations without influence；The sweetener is selected from sucrose and aspartame, can improve the withered taste of effervescent tablet solution, especially
It is that aspartame sugariness is high, it will not saprodontia；The aromatic is selected from the savory essence of orange, improves the bad smell of effervescent tablet solution,
It is easier to patient's receiving；The lubricant is selected from common soluble oil polyethylene glycol-6000, high lubricating effect；Institute
The adhesive stated is selected from most common water-soluble binder PVPK30, easy to dissolve, and above-mentioned dosage is selected to be more conducive to effervescent tablet
It prepares；The above auxiliary material is used in compounding with main ingredient, and the effervescent tablet for being easier to patient's receiving is made.
Beneficial effects of the present invention are：Escitalopram oxalate effervescent tablet in addition to having the advantages that conventional tablet, as
A kind of frothing solution taken orally as a solution, it is suitable for the patient that swallow tablet is had any problem；Again water is put into response to the used time
In cup, generation bubble disintegration phenomenon is intuitively interesting, and mouthfeel is again good, is well suited for the patient of mental disease.Since drug is with solution
Form is administered orally, then the problem related with dissolution, such as absorption rate and bioavilability it is low, can be to avoid bad shadow
It rings.
Specific implementation mode
Embodiment 1
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 17.75g, sodium bicarbonate 29.75g, sucrose 26.62g, orange savory essence 5.74g, aspartame 8.87g,
Polyethylene glycol-6000 7.83g, PVPK300.1g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, 80 mesh of polyethylene glycol-6000 sieving；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 40 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 2
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 20g, sodium bicarbonate 30g, sucrose 29.56g, orange savory essence 4g, aspartame 7g, polyethylene glycol-
6000 6g, PVPK300.1g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, 80 mesh of polyethylene glycol-6000 sieving；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 43 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 3
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 18.56g, sodium bicarbonate 30g, sucrose 28g, orange savory essence 5g, aspartame 8g, polyethylene glycol-
6000 7g, PVPK300.1g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, 80 mesh of polyethylene glycol-6000 sieving；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 65 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 40 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 4
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 17g, sodium bicarbonate 28.08g, sucrose 25g, orange savory essence 7.5g, aspartame 10g, polyethylene glycol-
6000 9g, PVPK300.08g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, polyethylene glycol-6000 crosses 80 mesh sieve；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 40 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 5
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 15g, sodium bicarbonate 26.04g, sucrose 24g, orange savory essence 8.5g, aspartame 12g, polyethylene glycol-
6000 11g, PVPK300.12g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, 80 mesh of polyethylene glycol-6000 sieving；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 45 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 6
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 14g, sodium bicarbonate 25g, sucrose 23g, orange savory essence 9.5g, aspartame 13.02g, polyethylene glycol-
6000 12g, PVPK300.14g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, 80 mesh of polyethylene glycol-6000 sieving；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 65 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 40 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 7
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 13g, sodium bicarbonate 25g, sucrose 22g, orange savory essence 9.51g, aspartame 14g, polyethylene glycol-
6000 13g, PVPK300.15g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, polyethylene glycol-6000 crosses 80 mesh sieve；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 45 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Embodiment 8
A kind of escitalopram oxalate effervescent tablet, component are by weight percentage：Escitalopram oxalate is
3.34g, anhydrous citric acid 22g, sodium bicarbonate 32.56g, sucrose 31g, orange savory essence 2g, aspartame 5g, polyethylene glycol-
6000 4g, PVPK300.1g；
Preparation method：
1. escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed, A Sipa
Smooth, polyethylene glycol-6000 crosses 80 mesh sieve；
2. weighing the escitalopram oxalate of recipe quantity, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed,
The PVPK of gross mass 38% is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
3. weighing the sodium bicarbonate of recipe quantity, sucrose, it is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, system
Softwood, the sieve granulation of 20 mesh, 40 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
4. the polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
5. selecting the flat molded tablets in a state of excitement of Ф 8mm, theoretical piece weight 191.6mg.
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol solution for being 50% with volume fraction is prepared
The PVPK for being 5% at mass fraction30Ethanol solution.
Comparative example 1
Certain mental hospital chooses the almost the same patient of 100 psychotics：50 patients take common oxalic acid Chinese mugwort
Citalopram tablet is taken charge of, wherein 30 patients take, 20 patient's refusals are taken, and it is 60% to comply with sex ratio；50 patient's clothes
With the effervescent tablet of the present invention, 48 patients take, and only 2 patient's refusals are taken, and it is 96% to comply with sex ratio.Although with common
Tablets form is the same, is oral, but effervescent tablet is easier to be accepted by patients.
Comparative example 2
The comparison of the dissolution degree of this effervescent tablet and other ordinary solid preparations, carried out this effervescent tablet of same size and
The comparison of ordinary tablet stripping curve in 4 kinds of media, it is as a result as follows：
The phosphate buffer of pH6.8：
This effervescent tablet and ordinary tablet are in pH6.8 phosphate buffers compared with stripping curve
| Time (min) | 0 | 5 | 10 | 15 | 30 | 45 |
| This effervescent tablet | 0 | 85.5% | 96.9% | 101.6% | 100.5% | 101.0% |
| Ordinary tablet | 0 | 61.0% | 74.6% | 80.4% | 89.3% | 92.3% |
Conclusion：In pH6.8 phosphate buffers, the dissolution of this effervescent tablet is significantly faster than that ordinary tablet, dissolution rate are obviously high
In ordinary tablet.
Water：
This effervescent tablet is compared with ordinary tablet in water stripping curve
| Time (min) | 0 | 5 | 10 | 15 | 30 | 45 |
| This effervescent tablet | 0 | 80.5% | 88.6% | 98.5% | 100.4% | 100.7% |
| Ordinary tablet | 0 | 63.4% | 64.5% | 77.4% | 78.2% | 85.0% |
Conclusion：In water, the dissolution of this effervescent tablet is significantly faster than that ordinary tablet, dissolution rate are apparently higher than ordinary tablet.
PH4.5 acetate buffers：
This effervescent tablet and ordinary tablet are in pH4.5 acetate buffers compared with stripping curve
| Time (min) | 0 | 5 | 10 | 15 | 30 | 45 |
| This effervescent tablet | 0 | 90.8% | 98.6% | 98.5% | 101.1% | 100.9% |
| Ordinary tablet | 0 | 59.7% | 66.6% | 78.3% | 88.2% | 90.5% |
Conclusion：In pH4.5 acetate buffers, the dissolution of this effervescent tablet is significantly faster than that ordinary tablet, dissolution rate are obviously high
In ordinary tablet.
0.1M hydrochloric acid：
This effervescent tablet and ordinary tablet are in 0.1M hydrochloric acid compared with stripping curve
| Time (min) | 0 | 5 | 10 | 15 | 30 | 45 |
| This effervescent tablet | 0 | 89.7% | 97.7% | 99.6% | 100.1% | 100.1% |
| Ordinary tablet | 0 | 71.2% | 78.3% | 86.0% | 87.9% | 91.4% |
Conclusion：In 0.1M hydrochloric acid, the dissolution of this effervescent tablet is significantly faster than that ordinary tablet, dissolution rate are apparently higher than ordinary tablet.
The result shows that：In four kinds of media, the dissolution rate and degree of this effervescent tablet are significantly better than that ordinary tablet.
Claims (3)
1. a kind of escitalopram oxalate effervescent tablet, it is characterised in that：The effervescent tablet component is calculated as by weight：Oxalic acid
1-10 parts of escitalopram, 13-23 parts of anhydrous citric acid, 25-35 parts of sodium bicarbonate, 22-32 parts of sucrose, the savory essence 1-11 of orange
Part, 4-14 parts of aspartame, 3-13 parts of polyethylene glycol-6000, PVPK300.05-0.15 parts；
Its preparation process is specially：
(1) it pre-processes：
Escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed by above-mentioned prescription, Ah
Si Patan, polyethylene glycol-6000 cross 80 mesh sieve, spare；
(2) it pelletizes：
It by the escitalopram oxalate pre-processed, anhydrous citric acid, aspartame, the savory essence of orange, is uniformly mixed, is added total
The PVPK of quality 38%30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of ± 5 DEG C of dryings, until pellet moisture≤1.0%, 18
Mesh sieve obtains particle a；
It by the sodium bicarbonate pre-processed, sucrose, is uniformly mixed, the PVPK of gross mass 62% is added30Ethanol solution, softwood processed,
The sieve granulation of 20 mesh, 40 DEG C of ± 5 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
(3) total mixed：
The polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
(4) tabletting：
Select the flat molded tablets in a state of excitement of Ф 8mm；
The PVPK30Ethanol solution is the PVPK in above-mentioned prescription30The ethanol water for being 50% with volume fraction is configured to
The PVPK that mass fraction is 5%30Ethanol solution.
2. effervescent tablet according to claim 1, it is characterised in that：The effervescent tablet component is calculated as by weight：Oxalic acid
3.34 parts of escitalopram, 17.75 parts of anhydrous citric acid, 29.75 parts of sodium bicarbonate, 26.62 parts of sucrose, orange savory smart 5.74
Part, 8.87 parts of aspartame, 7.83 parts of polyethylene glycol-6000, PVPK300.1 part.
3. a kind of escitalopram oxalate effervescent tablet preparation process, it is characterised in that：
The effervescent tablet component is calculated as by weight：1-10 parts of escitalopram oxalate, 13-23 parts of anhydrous citric acid, carbon
25-35 parts of sour hydrogen sodium, 22-32 parts of sucrose, savory 1-11 parts of the essence of orange, 4-14 parts of aspartame, 3-13 parts of polyethylene glycol-6000,
PVPK300.05-0.15 parts；
Preparation process is specially：
(1) it pre-processes：
Escitalopram oxalate, sodium bicarbonate, anhydrous citric acid, sucrose, savory smart 80 mesh of orange are crushed by above-mentioned prescription, Ah
Si Patan, polyethylene glycol-6000 cross 80 mesh sieve, spare；
(2) it pelletizes：
By the escitalopram oxalate pre-processed, anhydrous citric acid, aspartame, the savory essence of orange, it is uniformly mixed, is added
PVPK30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 60 DEG C of ± 5 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains
Particle a；
It by the sodium bicarbonate pre-processed, sucrose, is uniformly mixed, PVPK is added30Ethanol solution, softwood processed, the sieve granulation of 20 mesh, 40
DEG C ± 5 DEG C of dryings, until pellet moisture≤1.0%, 18 mesh sieve, obtains particle b；
(3) total mixed：
The polyethylene glycol-6000 of particle a, particle b and recipe quantity are uniformly mixed；
(4) tabletting：
Select the flat molded tablets in a state of excitement of Ф 8mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510732767.8A CN105343026B (en) | 2015-10-30 | 2015-10-30 | Escitalopram oxalate effervescent tablet formula and preparation process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510732767.8A CN105343026B (en) | 2015-10-30 | 2015-10-30 | Escitalopram oxalate effervescent tablet formula and preparation process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105343026A CN105343026A (en) | 2016-02-24 |
| CN105343026B true CN105343026B (en) | 2018-09-11 |
Family
ID=55319191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510732767.8A Active CN105343026B (en) | 2015-10-30 | 2015-10-30 | Escitalopram oxalate effervescent tablet formula and preparation process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105343026B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111514110A (en) * | 2020-05-07 | 2020-08-11 | 福建海西新药创制有限公司 | Pharmaceutical composition containing escitalopram oxalate and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103565788A (en) * | 2013-09-30 | 2014-02-12 | 北京德众万全药物技术开发有限公司 | Pharmaceutical composition for treating depression and preparation method thereof |
| CN104523638A (en) * | 2014-11-28 | 2015-04-22 | 浙江华海药业股份有限公司 | Tablet containing escitalopram oxalate and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013081567A1 (en) * | 2011-12-02 | 2013-06-06 | Mahmut Bilgic | Effervescent antipsychotic formulations |
| WO2013100870A1 (en) * | 2011-12-02 | 2013-07-04 | Mahmut Bilgic | New antipsychotic compositions |
-
2015
- 2015-10-30 CN CN201510732767.8A patent/CN105343026B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103565788A (en) * | 2013-09-30 | 2014-02-12 | 北京德众万全药物技术开发有限公司 | Pharmaceutical composition for treating depression and preparation method thereof |
| CN104523638A (en) * | 2014-11-28 | 2015-04-22 | 浙江华海药业股份有限公司 | Tablet containing escitalopram oxalate and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105343026A (en) | 2016-02-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2005945B1 (en) | Oseltamivir phosphate granule and preparation method thereof | |
| HU230771B1 (en) | Sustained release vitamin composition | |
| CN105534933A (en) | Vortioxetine orally disintegrating tablet and preparation method thereof | |
| CN102579415A (en) | Agomelatine-containing medicinal composition for oral mucosa or sublingual administration | |
| CN106511312A (en) | Compound sildennafil dapoxetine slow-release capsule and preparation method thereof | |
| CN105395504B (en) | A kind of flunarizine hydrochloride matrix sustained release tablet and preparation method thereof | |
| CN105343026B (en) | Escitalopram oxalate effervescent tablet formula and preparation process | |
| CN101991561B (en) | 3,4-dichlorophenyl-propenoyl-sec-butylamine composition | |
| CN103520111B (en) | A kind of florfenicol dry suspension and its production and use | |
| CN102114010B (en) | Medicinal composition for treating gastrointestinal disorders as well as preparation method and application thereof | |
| CN101584703B (en) | Pharmaceutical composition for treating colpitis and preparation method thereof | |
| CN103405510B (en) | Compound licorice preparation for eliminating phlegm and relieving cough and preparation method thereof | |
| CN105708808A (en) | Epinastine hydrochloride granule, and preparation method thereof | |
| CN103655574A (en) | Compound ferrous succinate and folic acid composition | |
| CN103222966A (en) | Solid pharmaceutical composition containing Fingolimod hydrochloride and preparation method thereof | |
| CN106511277A (en) | Polaprezinc granule and preparation method thereof | |
| CN104644580A (en) | Pharmaceutical composition of teneligliptin | |
| CN105769875A (en) | Preparation method of compound olanzapine fluoxetine hydrochloride capsule | |
| CN105982872B (en) | A kind of arctigenin tablet | |
| CN102973577B (en) | Compound sodium sulfaquinoxaline composition for treating coccidiosis in young rabbits, and preparation method thereof | |
| CN105357966A (en) | Method and products for enhancing drug and dietary supplement bioavailability | |
| CN102784116A (en) | High-dissolution fenofibrate dispersible tablet and preparation process thereof | |
| CN102225065B (en) | Parcetamol pseudoephedrine hydrochloride and dextromethorphan hydrochloride capsule and preparation method thereof | |
| CN102349882A (en) | Medicinal composition containing trandolapril and preparation process thereof | |
| CN106137994A (en) | A kind of stable tablet of clopidogrel and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Formulation and preparation technology of escitalopram oxalate effervescent tablets Effective date of registration: 20211230 Granted publication date: 20180911 Pledgee: Industrial Bank Co.,Ltd. Tai'an Branch Pledgor: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Registration number: Y2021980016939 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20230203 Granted publication date: 20180911 Pledgee: Industrial Bank Co.,Ltd. Tai'an Branch Pledgor: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Registration number: Y2021980016939 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Formulation and preparation process of escitalopram oxalate effervescent tablets Effective date of registration: 20230210 Granted publication date: 20180911 Pledgee: Industrial Bank Co.,Ltd. Tai'an Branch Pledgor: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Registration number: Y2023980032425 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Granted publication date: 20180911 Pledgee: Industrial Bank Co.,Ltd. Tai'an Branch Pledgor: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Registration number: Y2023980032425 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Formula and preparation process of oxalate escitalopram effervescent tablets Granted publication date: 20180911 Pledgee: Industrial Bank Co.,Ltd. Tai'an Branch Pledgor: JEWIM PHARMACEUTICAL (SHANDONG) CO.,LTD. Registration number: Y2024980004981 |