CN105395507B - A kind of cyclobenzaprine hydrochloride sustained release tablets - Google Patents
A kind of cyclobenzaprine hydrochloride sustained release tablets Download PDFInfo
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- CN105395507B CN105395507B CN201510887298.7A CN201510887298A CN105395507B CN 105395507 B CN105395507 B CN 105395507B CN 201510887298 A CN201510887298 A CN 201510887298A CN 105395507 B CN105395507 B CN 105395507B
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- cyclobenzaprine hydrochloride
- parts
- sustained release
- slow
- pore
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- 229960000500 cyclobenzaprine hydrochloride Drugs 0.000 title claims abstract description 31
- VXEAYBOGHINOKW-UHFFFAOYSA-N cyclobenzaprine hydrochloride Chemical compound Cl.C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 VXEAYBOGHINOKW-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 17
- 239000004088 foaming agent Substances 0.000 claims abstract description 9
- 239000000945 filler Substances 0.000 claims abstract description 4
- 239000000314 lubricant Substances 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 3
- 229920001285 xanthan gum Polymers 0.000 claims description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical group [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 claims 1
- 239000011148 porous material Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 239000003405 delayed action preparation Substances 0.000 abstract description 6
- 208000002193 Pain Diseases 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- 238000005516 engineering process Methods 0.000 abstract description 4
- 208000007101 Muscle Cramp Diseases 0.000 abstract description 3
- 239000012153 distilled water Substances 0.000 abstract description 2
- 210000002027 skeletal muscle Anatomy 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 206010028836 Neck pain Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003572 cyclobenzaprine Drugs 0.000 description 1
- JURKNVYFZMSNLP-UHFFFAOYSA-N cyclobenzaprine Chemical compound C1=CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 JURKNVYFZMSNLP-UHFFFAOYSA-N 0.000 description 1
- CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 208000017445 musculoskeletal system disease Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention provides a kind of preparation methods of cyclobenzaprine hydrochloride sustained release tablets, belong to pharmaceutical technology field.Cyclobenzaprine hydrochloride sustained release preparation of the present invention, is made of cyclobenzaprine hydrochloride, slow-release material, pore-foaming agent, filler, lubricant, distilled water.Wherein main component cyclobenzaprine hydrochloride has the effects that alleviate muscle cramp and its severe pain of adjoint skeletal muscle, provides one kind safely and effectively, stable quality is of low cost, and administration frequency is few, and patient's compliance enhances, and can steadily relieve pain the sustained release preparation of spasmolysis.
Description
Technical field
The invention belongs to pharmaceutical technology fields, are related to a kind of preparation method of cyclobenzaprine hydrochloride sustained release tablets, and the present invention carries
Supplied it is a kind of safely and effectively, stable quality is of low cost, and administration frequency is few, patient's compliance enhancing, can steadily relieve pain spasmolysis
Sustained release preparation.
Background technology
Cyclobenzaprine hydrochloride, entitled 5- (the 3- dimethylaminos propylene) dibenzo of chemistry;a,e]Cycloheptatriene hydrochloride, structure
Formula is：
Molecular formula：C20H21N·HCl
Molecular weight：311.85
Disease of the musculoskeletal system is more common in clinic, is related to bone, interverbebral disc, nerve, muscle, joint, soft tissue
Deng many-sided disease, the reason of causing musculoskeletal pain, is also very much, such as inflammation, mechanical injuries, immunology reason, tumour
Deng.Musculoskeletal pain occur it is frequent, while also according to the difference at invasion position, be classified as cervical pain, the back of the body and back pain,
Arthralgia etc..Usually long-term, chronic injury is caused to torment sufferer.
Cyclobenzaprine hydrochloride is developed by Merk companies earliest, 1978, and cyclobenzaprine hydrochloride piece lists in the U.S., rule
Lattice are 5mg, 10mg, and the muscle cramp adjoint for alleviating acute painful musculoskeletal disease is still that the U.S. is the most frequently used at present
One of muscle relaxant, not yet list at home.Cyclobenzaprine hydrochloride sustained release agent obtains U.S. FDA batch for the first time in August, 2007
Quasi- listing, this product is a kind of long-acting sustained release preparation, is the muscle relaxant of the only one of U.S. FDA approval by daily single,
As the auxiliary treatment of rest and physical therapy, for alleviating acute, the relevant muscle cramp of painful muscle skeletal diseases and its companion
With the symptom or signs such as pain, tenderness and limitation of activity, clinical application for many years, safely and effectively.
The cyclobenzaprine hydrochloride sustained release agent preparation method being currently known, CN103068375A are related to a kind of piece of cyclobenzaprine
Agent casing predominantly carries out repeatedly coating described in CN102065691A to form the sustained release bead of drug containing, and production technology is complicated, no
It is suitble to industrialized production.Present invention process is simple, and working condition easily meets, and is suitble to industrialized production.
Invention content
The present invention provides one kind safely and effectively, and stable quality is of low cost, and administration frequency is few, the enhancing of patient's compliance,
The sustained release preparation of spasmolysis can steadily be relieved pain.
The present invention takes disadvantage inconvenient, that bioavilability is low, invention to solve existing cyclobenzaprine hydrochloride preparation
Cyclobenzaprine hydrochloride sustained release tablets reduce medicining times, slow down absorption rate, extend biological half-life, and blood concentration control is made to exist
Within the scope of effective blood drug concentration, to reduce side effect, the compliance of patient is improved.
It has been found that existing be prepared into sustained-release tablet by cyclobenzaprine hydrochloride in conjunction with specific auxiliary material, high with stability,
Had good sustained release effect and the high advantage of bioavilability.
The application provides a kind of sustained-release tablet of cyclobenzaprine hydrochloride, including：
In this application, specific auxiliary material is selected to prepare cyclobenzaprine hydrochloride sustained-release tablet.The wherein described slow-release material is Huang
The composition of virgin rubber and hydroxypropyl methyl cellulose, the two weight ratio are 3:1, pore-foaming agent is microcrystalline cellulose, slow-release material
Ratio with pore-foaming agent is 3:2, filler is lactose, and lubricant is selected from magnesium stearate or talcum powder.It is demonstrated experimentally that not appointing
Meaning pharmacy customary adjuvant is suitable for preparing cyclobenzaprine hydrochloride sustained-release tablet, the hydrochloric acid ring benzene for selecting this specific auxiliary material to be prepared
Prick what woods sustained-release tablet was prepared in the effect of release, stability, pharmacokinetics etc. far better than other auxiliary materials
Cyclobenzaprine hydrochloride sustained-release tablet.
Preferably, the prescription of sustained-release tablet is（By weight）：
The present invention has effectively played effect of the sustained release preparation on analgesic spasmolysis class drug, works well, and it is few to take number,
Once a day, rear drug is taken slowly uniformly to discharge, can held stationary blood concentration, and of low cost, good patient compliance.
Specific implementation mode
Inventor screens prescription with the following method, and tablet is made in each prescription, is made 1000：
A. all medicines in prescription are weighed respectively（Except magnesium stearate）, 80 mesh sieve is crossed, is put into Wet mixed granulating machine, it is dry-mixed
5-10 minutes, appropriate distilled water wet mixing is added, discharging is shut down when material is slightly blocking, is pelletized with 16 mesh nylon screens；
B. wet granular is placed in drying tray, thickness generally in 2-3cm, is sent into baking oven, 50-60 DEG C of drying of temperature, drying
Particle dries in the air to room temperature, discharging, with 14 mesh nylon screen whole grains afterwards；
C. granule materials are put into three-dimensional motion mixer, and magnesium stearate is added, total 10-15 minutes mixed, tabletting, packaging.
The preparation of embodiment 1-6 cyclobenzaprine hydrochloride sustained release tablets
The supplementary material of according to the form below, is prepared as described above method, and the cyclobenzaprine hydrochloride sustained release tablets of six embodiments are made.
According to dissolution rate and drug release determination method（With reference to Chinese Pharmacopoeia four general rule characteristic check methods 0931 of version in 2015）,
Measure cyclobenzaprine hydrochloride dissolution rate of the cyclobenzaprine hydrochloride sustained release tablets obtained by embodiment 1-6 in 24 hours.Test knot
Fruit is shown in Table 2.
As known from Table 2, the cyclobenzaprine hydrochloride sustained release tablets of embodiment 1 discharge slowly and at the uniform velocity in 24 hours, and explanation is worked as
The weight ratio of slow-release material xanthans and hydroxypropyl methyl cellulose is 3:1, and the ratio of slow-release material and pore-foaming agent is 3:2
When obtained cyclobenzaprine hydrochloride spansule slow release effect it is best.
Cyclobenzaprine hydrochloride sustained-release tablet stability test
Factors influencing has been carried out to appearance, the content of the sustained-release tablet of embodiment 1-6.
（1）Hot test：Example 1-6 samples are laid in culture dish in right amount, are placed in 60 DEG C of insulating box and are placed
10 days, the 0th, 5,10 day during this, separately sampled product measured, and measurement result is shown in Table 3；
（2）High humidity test：Sample is taken to be laid in culture dish in right amount, under conditions of 25 DEG C of relative humidity RH70% ± 5%
It places 10 days, the 0th, 5,10 day during this, separately sampled product measure, and measurement result is shown in Table 3；
（3）Strong illumination is tested, and is taken sample to be laid in culture dish in right amount, is placed in light cupboard 4500Lx ± 500Lx's
Condition illumination 10 days, the 0th, 5,10 day during this, separately sampled product measure, and measurement result is shown in Table 3.
The amount of pore-foaming agent is reduced in embodiment 2, the amount of pore-foaming agent is improved in embodiment 3, and embodiment 4-6 changes two
The ratio of kind slow-release material, either two kinds of slow-release material ratios it can be seen from Dissolution Rate Testing and stability test result
Changed or slow-release material and pore-foaming agent ratio change, the cyclobenzaprine hydrochloride sustained-release tablet being prepared（It is real
Apply a 2-6）Stability significantly reduced relative to embodiment 1.
Claims (2)
1. a kind of cyclobenzaprine hydrochloride sustained release tablets, which is characterized in that count by ratio of weight and the number of copies, each component content is：
5-30 parts of cyclobenzaprine hydrochloride
15-60 parts of slow-release material
10-30 parts of pore-foaming agent
15-50 parts of filler
1-5 parts of lubricant
Distill appropriate amount of water
The wherein described slow-release material is the composition of xanthans and hydroxypropyl methyl cellulose, and the two weight ratio is 3:1, pore
Agent is microcrystalline cellulose, and the weight ratio of slow-release material and pore-foaming agent is 3:2, filler is lactose, and lubricant is selected from stearic acid
Magnesium or talcum powder.
2. cyclobenzaprine hydrochloride sustained release tablets described in accordance with the claim 1, which is characterized in that preferably, count by ratio of weight and the number of copies
, prescription is：
15 parts of cyclobenzaprine hydrochloride
22.5 parts of xanthans
Hydroxypropyl methyl cellulose 7.5
20 parts of microcrystalline cellulose
25 parts of lactose
3 parts of magnesium stearate
Distill appropriate amount of water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510887298.7A CN105395507B (en) | 2015-12-07 | 2015-12-07 | A kind of cyclobenzaprine hydrochloride sustained release tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510887298.7A CN105395507B (en) | 2015-12-07 | 2015-12-07 | A kind of cyclobenzaprine hydrochloride sustained release tablets |
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| Publication Number | Publication Date |
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| CN105395507A CN105395507A (en) | 2016-03-16 |
| CN105395507B true CN105395507B (en) | 2018-10-23 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107998094A (en) * | 2016-10-31 | 2018-05-08 | 顾世海 | A kind of tenofovir disoproxil fumarate sustained release tablets and preparation method thereof |
| CN107519142B (en) * | 2017-08-24 | 2021-02-26 | 正大制药（青岛）有限公司 | Cyclobenzaprine hydrochloride sublingual tablet and preparation method thereof |
| CN109316457B (en) * | 2018-11-26 | 2021-07-13 | 正大制药（青岛）有限公司 | Cyclobenzaprine hydrochloride sustained release preparation and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014167440A1 (en) * | 2013-03-26 | 2014-10-16 | Wockhardt Limited | Modified release pharmaceutical compositions of cyclobenzaprine or salts thereof |
| CN104352474A (en) * | 2014-11-21 | 2015-02-18 | 哈尔滨圣吉药业股份有限公司 | Cyclobenzaprine hydrochloride sustained release tablets and preparation method thereof |
| CN104473908A (en) * | 2014-11-21 | 2015-04-01 | 哈尔滨圣吉药业股份有限公司 | Cyclobenzaprine hydrochloride sustained release pellets and preparation method thereof |
-
2015
- 2015-12-07 CN CN201510887298.7A patent/CN105395507B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014167440A1 (en) * | 2013-03-26 | 2014-10-16 | Wockhardt Limited | Modified release pharmaceutical compositions of cyclobenzaprine or salts thereof |
| CN104352474A (en) * | 2014-11-21 | 2015-02-18 | 哈尔滨圣吉药业股份有限公司 | Cyclobenzaprine hydrochloride sustained release tablets and preparation method thereof |
| CN104473908A (en) * | 2014-11-21 | 2015-04-01 | 哈尔滨圣吉药业股份有限公司 | Cyclobenzaprine hydrochloride sustained release pellets and preparation method thereof |
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| CN105395507A (en) | 2016-03-16 |
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Address after: 266000 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Applicant after: CP PHARMACEUTICAL (QINGDAO) Co.,Ltd. Address before: 266000 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Applicant before: Qingdao Zhengda Haier Pharmaceutical Co.,Ltd. |
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Address after: No.3601 Tuanjie Road, Qingdao Economic and Technological Development Zone, Shandong Province 266426 Patentee after: Qingdao Guoxin Pharmaceutical Co.,Ltd. Country or region after: China Address before: 266000 3601 Tuen Jie Road, Qingdao economic and Technological Development Zone, Shandong Patentee before: CP PHARMACEUTICAL (QINGDAO) Co.,Ltd. Country or region before: China |