CN115737584A - Carbamodidopa sustained release tablet and preparation method thereof - Google Patents
Carbamodidopa sustained release tablet and preparation method thereof Download PDFInfo
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- CN115737584A CN115737584A CN202211492343.5A CN202211492343A CN115737584A CN 115737584 A CN115737584 A CN 115737584A CN 202211492343 A CN202211492343 A CN 202211492343A CN 115737584 A CN115737584 A CN 115737584A
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- carbidopa
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- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 claims abstract description 49
- 239000000314 lubricant Substances 0.000 claims abstract description 19
- 239000000463 material Substances 0.000 claims abstract description 17
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims abstract description 16
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960004205 carbidopa Drugs 0.000 claims abstract description 15
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 claims abstract description 15
- 229920001577 copolymer Polymers 0.000 claims abstract description 15
- 229960004502 levodopa Drugs 0.000 claims abstract description 15
- 239000000853 adhesive Substances 0.000 claims abstract description 11
- 230000001070 adhesive effect Effects 0.000 claims abstract description 11
- 239000003086 colorant Substances 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 21
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 238000007906 compression Methods 0.000 claims description 15
- 230000006835 compression Effects 0.000 claims description 15
- 239000003826 tablet Substances 0.000 claims description 15
- 238000007873 sieving Methods 0.000 claims description 13
- 239000002245 particle Substances 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 239000008187 granular material Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 238000007908 dry granulation Methods 0.000 claims description 10
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 9
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 9
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 7
- 238000013268 sustained release Methods 0.000 claims description 7
- 239000012730 sustained-release form Substances 0.000 claims description 7
- 235000020985 whole grains Nutrition 0.000 claims description 6
- 244000248349 Citrus limon Species 0.000 claims description 5
- 235000005979 Citrus limon Nutrition 0.000 claims description 5
- 238000013461 design Methods 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- IZMJMCDDWKSTTK-UHFFFAOYSA-N quinoline yellow Chemical compound C1=CC=CC2=NC(C3C(C4=CC=CC=C4C3=O)=O)=CC=C21 IZMJMCDDWKSTTK-UHFFFAOYSA-N 0.000 claims description 2
- 229940051201 quinoline yellow Drugs 0.000 claims description 2
- 235000012752 quinoline yellow Nutrition 0.000 claims description 2
- 239000004172 quinoline yellow Substances 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 229940052036 carbidopa / levodopa Drugs 0.000 claims 2
- 238000013265 extended release Methods 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 2
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- 230000000052 comparative effect Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 3
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 2
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- 206010006100 Bradykinesia Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
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Abstract
The invention relates to the technical field of pharmacy, and particularly discloses a carbidopa-levodopa sustained release tablet and a preparation method thereof. The carbidopa-levodopa sustained release tablet comprises the following raw material components in percentage by mass: 65.6 to 67.7 percent of levodopa, 17.7 to 18.3 percent of carbidopa, 6.0 to 8.9 percent of slow release material, 5.9 to 6.1 percent of dry adhesive, 0.3 to 0.4 percent of colorant and 1.4 to 1.6 percent of lubricant. The invention takes levodopa and carbidopa as active ingredients, selects polylactic acid-glycolic acid copolymer as a slow release material, and is assisted by dry adhesive, colorant and lubricant, thereby realizing effective control on the release speed of the carbidopa and the levodopa.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to a carbidopa-levodopa sustained release tablet and a preparation method thereof.
Background
The carbidopa-levodopa compound preparation is a compound preparation of levodopa and carbidopa, is firstly developed and marketed by Moshadong pharmaceutical company Limited, and is an imported original preparation with the trade name of ' xining ', which is one of main medicines for relieving and treating Parkinson's disease symptoms. After the levodopa and the carbidopa are used together, the small dose of levodopa can reach the effective dopamine brain concentration, so that symptoms of rigidity, bradykinesia, balance disorder, tremor and the like of the Parkinson disease are improved.
In the preparation process of the carbidopa-levodopa sustained release tablet, because the direct tabletting process is difficult to obtain ideal fluidity and compressibility, a wet granulation process is required to improve the fluidity of powder, however, hydroxypropyl cellulose and hydroxypropyl cellulose are often used as sustained release materials in the existing preparation method, the granulation state is difficult to control in the wet granulation process due to large viscosity and large dosage, the risk of unqualified hardness or sticky impact during subsequent tabletting exists, the good reproducibility is not achieved, and carbidopa is relatively unstable when meeting moisture, so that the effectiveness of the tablet is influenced; in addition, some carbidopa-levodopa sustained-release tablets reported in the literature at present have poor stability, and the dissolution rate is poor in consistency with that of the original research. Therefore, the research and development of the carbidopa-levodopa sustained release tablet which has good consistency with the original product, high production safety and low cost has very important significance.
Disclosure of Invention
In view of the above, the invention provides a carbidopa-levodopa sustained release tablet and a preparation method thereof, wherein a polylactic acid-glycolic acid copolymer is selected as a sustained release material, and the polylactic acid-glycolic acid copolymer and hydroxypropyl cellulose can be synergistically sustained released, so that the release rate of carbidopa and levodopa can be effectively controlled, the stability of a product can be improved, the bioavailability of a drug in a body can be improved, and the original ground product can be well replaced.
In order to achieve the purpose, the invention adopts the following technical scheme:
a carbidopa-levodopa sustained release tablet comprises the following raw material components in percentage by mass: 65.6 to 67.7 percent of levodopa, 17.7 to 18.3 percent of carbidopa, 6.0 to 8.9 percent of slow release material, 5.9 to 6.1 percent of dry adhesive, 0.3 to 0.4 percent of colorant and 1.4 to 1.6 percent of lubricant;
wherein the slow release material is polylactic acid-glycolic acid copolymer, and the dry adhesive is hydroxypropyl cellulose.
Compared with the prior art, the carbidopa-levodopa sustained-release tablet provided by the invention selects the polylactic acid-glycolic acid copolymer with good biocompatibility and biodegradability as the sustained-release material, and the polylactic acid-glycolic acid copolymer and the hydroxypropyl cellulose can be synergistically sustained-released, so that the release speed of the carbidopa and the levodopa is effectively controlled, the stability of the preparation can be improved, and the increase of impurity content in the preparation and storage processes is reduced. The prepared carbidopa-levodopa sustained release tablet has good stability, high bioavailability, long effective blood concentration maintenance time, good sustained release effect, drug release curve highly consistent with the original preparation, greatly reduced drug administration cost, and improved clinical drug administration safety.
Optionally, the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 7-8:2-3. The invention improves the stability of the drug release rate by adjusting the component proportion of the polylactic acid-glycolic acid copolymer, avoids the excessively fast or slow release rate, prolongs the maintenance time of the blood drug concentration, ensures that the drug can be stably released after entering the body, has low burst release and improves the safety of medication.
Optionally, the colorant is at least one of red iron oxide, lemon yellow aluminum lake or quinoline yellow aluminum lake.
Optionally, the lubricant is one of calcium stearate, sodium stearyl fumarate or magnesium stearate.
In some other embodiments, the carbidopa-levodopa sustained release tablet comprises the following raw material components in percentage by mass: 66.6 to 66.7 percent of levodopa, 18 percent of carbidopa, 7.5 percent of slow release material, 6 percent of dry adhesive, 0.3 to 0.4 percent of colorant and 1.5 percent of lubricant.
The invention also provides a preparation method of the carbidopa-levodopa sustained release tablet, which comprises the following steps:
weighing the components according to a design ratio, sieving, and adding the sieved levodopa, carbidopa, slow release materials, dry adhesives, coloring agents and part of lubricants into a granulator for premixing to obtain a premix; wherein the adding amount of the partial lubricant is 50-67% of the total mass of the lubricant;
step two, dry granulation, granule finishing and sieving are sequentially carried out on the premix to obtain granules;
and step three, uniformly mixing the granules and the balance of the lubricant, and tabletting to obtain the carbidopa-levodopa sustained release tablet.
Compared with the prior art, the preparation method of the carbidopa-levodopa sustained release tablet provided by the invention has the advantages that levodopa and carbidopa are taken as active ingredients, sustained release materials, dry adhesives, colorants and lubricants are used as auxiliary materials, and the proportion of the main drug and the auxiliary materials is controlled, so that the particle size uniformity is improved, the bulk density is increased, the flowability is good, the compressibility is good, the stability of the product is improved, the bioavailability of the drug in vivo is improved, and the original ground product is well replaced; meanwhile, a dry granulation process is adopted in the preparation process, so that the prepared granules have good fluidity, the requirement of producing tabletting is met, the problem of sticking and punching during tabletting is solved, the materials can be kept dry, the problem that carbidopa is easy to degrade in a humid environment and further the drug effect is influenced is avoided, coating treatment is not needed, the operation is simple, the cost is low, and the industrial large-scale production is easy.
Optionally, in the first step, the number of the sieved meshes is 20.
Optionally, in the first step, in the premixing process, the stirring rotation speed is 100rpm to 150rpm, and the premixing time is 5min to 10min.
Optionally, in the second step, in the dry granulation process, the feeding speed is 25.0rpm to 45.0rpm, the rotation speed of the compression roller is 7.0rpm to 13.0rpm, the oil pressure of the compression roller is 40bar to 50bar, the gap between the compression rollers is 0.5mm to 1.5mm, the crushing rotation speed is 80rpm to 160rpm, and the whole grain rotation speed is 80rpm to 150rpm. The optimized granulating process parameters are beneficial to improving the uniformity of the components of the medicine granules and ensuring the consistency of the product quality, and the prepared granules are fine and uniform and have good fluidity.
Optionally, in the step two, the whole grain is crushed by passing through a sieve with an aperture of 1.5mm, and then passes through a sieve with an aperture of 1.0mm to complete the grain.
Optionally, in the second step, the sieving is to sequentially pass through 20-mesh and 80-mesh sieves, and collect 20-80-mesh particles.
Optionally, in the third step, in the mixing step, the mixing rotation speed is 10rpm to 15rpm, and the mixing time is 5min to 10min.
Optionally, in the third step, the hardness of the compressed tablet is 70N-110N. The optimized hardness of the tablet is beneficial to improving the consistency of the dissolution rate of the carbidopa-levodopa sustained release tablet and the original preparation.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
This example provides a carbidopa-levodopa sustained release tablet, and the dosage (3000 tablets) of the prescription is shown in the following table:
the preparation method of the carbidopa-levodopa sustained release tablet comprises the following steps:
weighing the components according to a design ratio, sequentially sieving levodopa, carbidopa, polylactic acid-glycolic acid copolymer, hydroxypropyl cellulose, red ferric oxide, lemon yellow aluminum lake and magnesium stearate through a 20-mesh sieve, adding into a multifunctional granulator, and premixing for 8min at a rotating speed of 120rpm to obtain a premix; wherein the addition amount of the magnesium stearate is 9g;
step two, performing dry granulation on the premix, crushing the prepared dry extruded sheet by a 1.5mm screen, finishing the crushed block or particles by a 1.0mm screen, sieving the finished particles by 20-mesh and 80-mesh rotary vibration sieve meshes, repeatedly performing dry granulation on fine powder smaller than 80-mesh until the fine powder is not enough to perform granulation, and collecting 20-80-mesh particles; wherein the feeding speed in the granulating process is 30.0rpm, the rotating speed of a compression roller is 10rpm, the oil pressure of the compression roller is controlled to be 45bar, the gap between the compression rollers is 1.0mm, the crushing rotating speed is 120rpm, and the whole grain rotating speed is 110rpm;
and step three, adding the granules into a multifunctional granulator, adding the rest magnesium stearate, mixing for 8min at the rotating speed of 12rpm, adding the mixture into a hopper of a high-speed rotary tablet press, starting tabletting, and controlling the hardness of the tablets to be 90N to obtain the carbidopa-levodopa sustained release tablet.
Example 2
This example provides a carbidopa-levodopa sustained release tablet, and the dosage (3000 tablets) of the prescription is shown in the following table:
the preparation method of the carbidopa-levodopa sustained release tablet comprises the following steps:
weighing the components according to a design ratio, sequentially sieving levodopa, carbidopa, polylactic acid-glycolic acid copolymer, hydroxypropyl cellulose, red ferric oxide, lemon yellow aluminum lake and magnesium stearate through a 20-mesh sieve, adding into a multifunctional granulator, and premixing for 5min at a rotating speed of 100rpm to obtain a premix; wherein the addition amount of magnesium stearate is 9g;
step two, performing dry granulation on the premix, crushing the prepared dry extruded sheet by a 1.5mm screen, finishing the crushed block or particles by a 1.0mm screen, sieving the finished particles by 20-mesh and 80-mesh rotary vibration sieve meshes, repeatedly performing dry granulation on fine powder smaller than 80-mesh until the fine powder is not enough to perform granulation, and collecting 20-80-mesh particles; wherein the feeding speed in the granulating process is 25.0rpm, the rotation speed of the compression roller is 7.0rpm, the oil pressure of the compression roller is controlled to be 40bar, the gap between the compression rollers is 0.5mm, the crushing rotation speed is 80rpm, and the whole granulating rotation speed is 80rpm;
and step three, adding the granules into a multifunctional granulator, adding the rest lubricant, mixing for 5min at the rotating speed of 10rpm, adding the mixture into a hopper of a high-speed rotary tablet press, starting tabletting, and controlling the hardness of the tablets to be 70N to obtain the carbidopa-levodopa sustained release tablet.
Example 3
This example provides a carbidopa-levodopa sustained release tablet, and the dosage (3000 tablets) of the prescription is shown in the following table:
the preparation method of the carbidopa-levodopa sustained release tablet comprises the following steps:
weighing the components according to a design ratio, sequentially sieving levodopa, carbidopa, polylactic acid-glycolic acid copolymer, hydroxypropyl cellulose, red ferric oxide, lemon yellow aluminum lake and magnesium stearate through a 20-mesh sieve, adding into a multifunctional granulator, and premixing for 10min at a rotating speed of 150rpm to obtain a premix; wherein the addition amount of magnesium stearate is 9g;
step two, performing dry granulation on the premix, crushing the prepared dry extruded sheet by a 1.5mm screen, finishing the crushed block or particles by a 1.0mm screen, sieving the finished particles by 20-mesh and 80-mesh rotary vibration sieve meshes, repeatedly performing dry granulation on fine powder smaller than 80-mesh until the fine powder is not enough to perform granulation, and collecting 20-80-mesh particles; wherein the feeding speed in the granulating process is 45.0rpm, the rotation speed of a compression roller is 13.0rpm, the oil pressure of the compression roller is controlled to be 50bar, the gap between the compression rollers is 1.5mm, the crushing rotation speed is 160rpm, and the whole grain rotation speed is 150rpm;
and step three, adding the granules into a multifunctional granulator, adding the rest lubricant, mixing for 10min at the rotating speed of 15rpm, adding the mixture into a hopper of a high-speed rotary tablet press, starting tabletting, and controlling the hardness of the tablets to be 110N to obtain the carbidopa-levodopa sustained release tablet.
While preparing embodiments of the present invention, the inventors have also studied other different formulations, as follows:
comparative example 1
The comparative example provides a carbidopa-levodopa sustained-release tablet and a preparation method thereof, and the difference from example 1 is that polylactic acid-glycolic acid copolymer is replaced by equal amount of hypromellose.
Comparative example 2
The comparative example provides a carbidopa-levodopa sustained release tablet and a preparation method thereof, and the difference from example 1 is that the addition amount of the polylactic acid-glycolic acid copolymer is 90g.
In order to examine the in vitro dissolution effect of the carbidopa-levodopa sustained release tablets prepared in examples 1 to 3 and comparative examples 1 to 2 of the present invention, an in vitro dissolution test was performed in a hydrochloric acid medium.
The dissolution rate detection method comprises the following steps: according to the FDA dissolution method-paddle method, the rotation speed is 50r/min, 900mL of hydrochloric acid solution with the pH value of 1.0 is taken as a dissolution medium, and the HPLC method is used for detecting the cumulative dissolution of each tablet in 0.5h, 0.75h, 1h, 2h, 3h, 4h, 6h and 8h respectively. The dissolution test results of the samples are shown in tables 1-2.
TABLE 1 dissolution testing results for samples
TABLE 2 dissolution testing results for samples
Note: the original preparation is a carbidopa-levodopa sustained-release tablet (xining) produced by Moshadong pharmaceutical Limited company, and the batch number is as follows: t035300.
As can be seen from tables 1-2, the sustained-release effect of the carbidopa-levodopa sustained-release tablet prepared in embodiments 1-3 of the invention is stable, the consistency with the dissolution curve of the original grinding agent is good, and the original grinding product can be replaced; and the preparation production process is simple, and the industrial large-scale production is easy to realize.
Three batches of levodopa and dopa sustained release tablets were prepared according to the recipe and preparation method of example 1, respectively, and then subjected to in vitro dissolution profile testing according to the dissolution method described above, with the results shown in tables 3-4.
TABLE 3 dissolution results for three batches of the sample of example 1
Table 4 dissolution results for three samples of example 1
As can be seen from tables 3-4, the sustained release tablets of carbidopa and levodopa prepared by the invention have the advantages of stable process, small batch difference and good reproducibility.
In order to examine the stability of the carbidopa-levodopa sustained release tablet prepared in the embodiment of the invention, according to the requirements of the general rules of the four ministry of the national pharmacopoeia 2020 edition of the stability test guiding principles of raw material drugs and pharmaceutical preparations and the ICH Q1A Q B, the carbidopa-levodopa sustained release tablet prepared in the embodiment 1 and the original preparation are respectively subjected to accelerated test and long-term test investigation, samples are respectively taken at 0 month, 3 months and 6 months for dissolution test, related substances and content measurement, the change of key quality attributes is examined, and the test results are shown in tables 5-6.
Table 5 example 1 dissolution test results
Table 6 example 1 test results for related substances and amounts
As can be seen from tables 5-6, compared with the original preparation, the carbidopa-levodopa sustained release tablet prepared in the embodiment 1 of the invention has no obvious change in dissolution rate, related substances and content after 6-month accelerated test and long-term test, and the product quality is equal to or superior to that of the original preparation. The invention effectively reduces the increase of impurity content in the storage process by selecting the adjuvant and adjusting the proportion, and is beneficial to improving the curative effect and the medication safety of the carbidopa-levodopa sustained release tablet.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The carbidopa-levodopa sustained release tablet is characterized by comprising the following raw material components in percentage by mass: 65.6 to 67.7 percent of levodopa, 17.7 to 18.3 percent of carbidopa, 6.0 to 8.9 percent of slow release material, 5.9 to 6.1 percent of dry adhesive, 0.3 to 0.4 percent of colorant and 1.4 to 1.6 percent of lubricant;
the slow-release material is polylactic acid-glycolic acid copolymer, and the dry adhesive is hydroxypropyl cellulose.
2. The carbidopa-levodopa sustained release tablet of claim 1, wherein the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is 7-8:2-3.
3. The extended release carbidopa/levodopa tablet of claim 1, wherein the colorant is at least one of red iron oxide, lemon yellow aluminum lake, or quinoline yellow aluminum lake.
4. The sustained-release carbidopa/levodopa tablet of claim 1, wherein the lubricant is one of calcium stearate, sodium stearyl fumarate, or magnesium stearate.
5. The carbidopa-levodopa sustained release tablet according to any one of claims 1 to 4, comprising the following raw material components by mass: 66.6 to 66.7 percent of levodopa, 18 percent of carbidopa, 7.5 percent of slow release material, 6 percent of dry adhesive, 0.3 to 0.4 percent of colorant and 1.5 percent of lubricant.
6. A preparation method of the carbidopa-levodopa sustained release tablet according to any one of claims 1 to 5, characterized by comprising the following steps:
weighing the components according to a design ratio, sieving, and adding the sieved levodopa, carbidopa, slow release materials, dry adhesives, coloring agents and part of lubricants into a granulator for premixing to obtain a premix; wherein the adding amount of the partial lubricant is 50-67% of the total mass of the lubricant;
step two, dry granulating, granulating and sieving the premix in sequence to obtain granules;
and step three, uniformly mixing the granules and the balance of the lubricant, and tabletting to obtain the carbidopa-levodopa sustained release tablet.
7. The method for preparing carbidopa-levodopa sustained release tablets according to claim 6, characterized in that: in the first step, the sieving mesh number is 20 meshes.
8. The method for preparing a carbidopa-levodopa sustained release tablet as claimed in claim 6, wherein the method comprises the following steps: in the first step, in the premixing procedure, the stirring speed is 100 rpm-150 rpm, and the premixing time is 5 min-10 min.
9. The method for preparing carbidopa-levodopa sustained release tablets according to claim 6, characterized in that: in the dry granulation process, the feeding speed is 25.0-45.0 rpm, the rotation speed of a compression roller is 7.0-13.0 rpm, the oil pressure of the compression roller is 40-50 bar, the gap between the compression rollers is 0.5-1.5 mm, the crushing rotation speed is 80-160 rpm, and the whole grain rotation speed is 80-150 rpm; and/or
In the step two, the whole grain is firstly crushed by a screen with the aperture of 1.5mm, and then is granulated by a screen with the aperture of 1.0 mm; and/or
In the second step, the sieving is to sequentially pass through 20-mesh and 80-mesh sieves, and collect 20-80-mesh particles.
10. The method for preparing carbidopa-levodopa sustained release tablets according to claim 6, characterized in that: in the third step, in the mixing procedure, the mixing speed is 10rpm to 15rpm, and the mixing time is 5min to 10 min; and/or
In the third step, the hardness of the tabletted tablet is 70N-110N.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211492343.5A CN115737584A (en) | 2022-11-25 | 2022-11-25 | Carbamodidopa sustained release tablet and preparation method thereof |
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| CN202211492343.5A CN115737584A (en) | 2022-11-25 | 2022-11-25 | Carbamodidopa sustained release tablet and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4832957A (en) * | 1987-12-11 | 1989-05-23 | Merck & Co., Inc. | Controlled release combination of carbidopa/levodopa |
| US20130195973A1 (en) * | 2012-01-30 | 2013-08-01 | Ranbaxy Laboratories Limited | Extended release pharmaceutical dosage forms of carbidopa and levodopa and process of preparation thereof |
| CN112773781A (en) * | 2020-12-31 | 2021-05-11 | 浙江美华鼎昌医药科技有限公司 | Carlevodopa and dopa sustained-release tablet and preparation method thereof |
-
2022
- 2022-11-25 CN CN202211492343.5A patent/CN115737584A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4832957A (en) * | 1987-12-11 | 1989-05-23 | Merck & Co., Inc. | Controlled release combination of carbidopa/levodopa |
| US20130195973A1 (en) * | 2012-01-30 | 2013-08-01 | Ranbaxy Laboratories Limited | Extended release pharmaceutical dosage forms of carbidopa and levodopa and process of preparation thereof |
| CN112773781A (en) * | 2020-12-31 | 2021-05-11 | 浙江美华鼎昌医药科技有限公司 | Carlevodopa and dopa sustained-release tablet and preparation method thereof |
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| Title |
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| 刘隆臻等: "《2018全国卫生专业技术资格考试指定用书 药学（士）资格考试 拿分考点随身记》", 中国医药科技出版社 * |
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