CN110227067B - Pramipexole dihydrochloride sustained-release tablet and preparation method thereof - Google Patents
Pramipexole dihydrochloride sustained-release tablet and preparation method thereof Download PDFInfo
- Publication number
- CN110227067B CN110227067B CN201910497313.5A CN201910497313A CN110227067B CN 110227067 B CN110227067 B CN 110227067B CN 201910497313 A CN201910497313 A CN 201910497313A CN 110227067 B CN110227067 B CN 110227067B
- Authority
- CN
- China
- Prior art keywords
- percent
- pramipexole
- sustained
- microcrystalline cellulose
- release
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Abstract
The pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%, 0.12% -0.45% of pramipexole hydrochloride, 50% -60% of filler, 25% -35% of sustained-release matrix, 8% -12% of adhesive, 0.3% -3% of glidant, 0.1% -1.0% of lubricant, the sustained-release matrix is Eudragit RD, hydroxypropyl methylcellulose K100M or a combination thereof, and the preferred combination is the combination of Eudragit RD and hydroxypropyl methylcellulose K100M; the ratio of glidant to lubricant is glidant: the lubricant is 0.5-10, preferably 0.6-8.
Description
Technical Field
The invention relates to a preparation process of pramipexole dihydrochloride sustained-release tablets, belonging to the field of medicinal preparations.
Background
Parkinson's Disease (PD) is a chronic progressive disease whose main pathological feature is degeneration of dopaminergic neurons of the substantia nigra striatum, leading to a decrease in dopaminergic neurons of the dopaminergic nerve endings and the striatum, with clinical symptoms manifested as paralysis agitans, rigidity or dyskinesia.
Pramipexole (Pramipexole), also known as melappa, is a dopamine D2 receptor agonist, is an antihistamine drug, and is mainly used for clinically treating parkinson's disease and syndromes thereof. The usual pharmaceutical form of the drug is pramipexole dihydrochloride monohydrate (formula C)10H17N3S·2HCl·H2O), is a highly soluble compound with a water solubility greater than 20mg/ml and a solubility in buffer media between pH 2 and 7.4 generally above 10 mg/ml. PramipexoleThe dihydrochloride monohydrate has extremely low hygroscopicity and high crystallinity, and its crystal modification does not change in a ground state. Pramipexole dihydrochloride monohydrate is very stable in the solid state, but is photosensitive in the solution state.
In 1997 pramipexole immediate release tablets (IR) were approved in USA for marketing, but due to the problem of unstable storage of the tablets, there was only about 95% of the average labeled amount of active ingredient in the tablets after 18 months of storage, which affected the efficacy of the drug and increased the cost and safety of manufacturing and patient administration.
Pramipexole dihydrochloride sustained release tablets Mirapex ER developed by Boehringer Ingelheim pharmaceutical ltd was approved by the FDA in the united states in 2010 and was taken once daily for treatment of signs and symptoms of early and advanced parkinson patients.
Mirapex ER original manufacturer patent (CN101005831) adopts a powder direct pressing process, and auxiliary materials comprise: hydroxypropyl methylcellulose, corn starch, carbomer homopolymer, colloidal silicon dioxide and magnesium stearate are prepared by grinding active ingredients and partial auxiliary materials together, and mixing with other auxiliary materials, wherein the pramipexole has small specification, such as 0.375mg, 0.75mg, 1.5mg, 2.25mg, 3mg, 3.75mg and 4.5mg, so that the content difference among tablets is large, and the content uniformity is difficult to ensure.
In addition, the release of the commercial preparation Mirapex ER is greatly influenced by ionic strength, and the release is higher in vitro in media with pH1.2, pH4.5 and pH6.8, while the release is lower in water, and the release is only about 20% in 24 h. Due to the complex variation of ionic strength in the human gastrointestinal tract, the release of the commercial formulation Mirapex ER in vivo is difficult to control.
Chinese patent CN201210351475.6 discloses a pramipexole dihydrochloride sustained release tablet, which mainly comprises pramipexole dihydrochloride, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose and magnesium stearate, and the preparation process thereof adopts a granulator to granulate and then dry the tablets.
Chinese patent CN201310186202.5 discloses a pramipexole dihydrochloride sustained-release preparation, which mainly comprises pramipexole dihydrochloride, hydroxypropyl methylcellulose, starch, hydroxypropyl cellulose, micro-ingredients and magnesium stearate, and the preparation process adopts direct powder tabletting and also has the problem of low uniformity.
Disclosure of Invention
In order to solve the technical problems, the inventor provides a preparation method of a pramipexole sustained-release tablet preparation, a powder direct compression method is used, the flowability of the material is improved by optimizing the ratio of a flow aid and a lubricant, the obtained granules have good flowability and compressibility, the content uniformity of the prepared product is good, the content difference is small, the drug release rate of the drug from the preparation is delayed by setting the combination ratio of sustained-release matrixes, and the in-vitro release is not influenced by the pH change.
The invention provides a pramipexole sustained-release tablet, which is prepared from the following components in percentage by weight:
| components | Mass percentage content (%) |
| Pramipexole dihydrochloride | 0.12-0.45 |
| Filler | 50-60 |
| Sustained release matrices | 25-35 |
| Adhesive agent | 8-12 |
| Glidants | 0.3-3 |
| Lubricant agent | 0.1-1.0 |
Wherein the slow release matrix is Eudragit RD, hypromellose K100M or their combination, preferably Eudragit RD and hypromellose K100M;
the ratio of glidant to lubricant is glidant: the lubricant is 0.5-10, preferably 0.6-8.
In the technical scheme of the invention, the slow release matrix is a combination of Eudragit RD and hypromellose K100M; and the mass ratio of the Eudragit RD to the hypromellose K100M is 1.3-3: 1.
In the technical scheme of the invention, the filler is selected from one or more of microcrystalline cellulose, lactose, anhydrous calcium hydrogen phosphate and corn starch; preferably, the microcrystalline cellulose is microcrystalline cellulose 102, microcrystalline cellulose 112, or a combination thereof; more preferably microcrystalline cellulose in combination with anhydrous dibasic calcium phosphate.
In the technical scheme of the invention, the adhesive is selected from hypromellose K4M, povidone K29/32 or a combination thereof.
In the technical scheme of the invention, the glidant is selected from sodium stearyl fumarate, talcum powder, superfine silica gel powder or a combination thereof.
In the technical scheme of the invention, the lubricant is selected from magnesium stearate, glyceryl behenate or a combination thereof.
In the technical scheme of the invention, the pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%: 0.12 to 0.18 percent of pramipexole dihydrochloride, 3 to 36 percent of microcrystalline cellulose 1023, 22 to 24 percent of anhydrous calcium hydrophosphate, 17 to 19 percent of Eudragit RD, 10 to 14 percent of hydroxypropyl methylcellulose K100M 10, 4 to 11 percent of hydroxypropyl methylcellulose K4M 9, 0.3 to 0.5 percent of sodium stearyl fumarate and 0.2 to 0.4 percent of magnesium stearate.
In the technical scheme of the invention, the pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%: 0.12 to 0.18 percent of pramipexole dihydrochloride, 11233 to 36 percent of microcrystalline cellulose, 22 to 24 percent of anhydrous calcium hydrophosphate, 20 to 22 percent of Eudragit RD, 6 to 8 percent of hydroxypropyl methylcellulose K100M 6, 0 to 12 percent of povidone K29/3210 percent, 0.4 to 0.6 percent of sodium stearyl fumarate and 0.7 to 0.9 percent of glyceryl behenate.
In the technical scheme of the invention, the pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%: 0.3 to 0.5 percent of pramipexole dihydrochloride, 3 to 36 percent of microcrystalline cellulose 1023, 23 to 25 percent of anhydrous calcium hydrophosphate, 20 to 22 percent of Eudragit RD, 6 to 9 percent of hydroxypropyl methylcellulose K100M 6, 4 to 11 percent of hydroxypropyl methylcellulose K4M 9, 0.8 to 1.2 percent of talcum powder and 0.4 to 0.6 percent of magnesium stearate.
In the technical scheme of the invention, the pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%: 0.15 to 0.35 percent of pramipexole dihydrochloride, 10235 to 38 percent of microcrystalline cellulose, 17 to 19 percent of anhydrous calcium hydrophosphate, 16 to 20 percent of Eudragit RD, 12 to 15 percent of hydroxypropyl methylcellulose K100M 12, 0 to 12 percent of povidone K29/3210, 1 to 3 percent of sodium stearyl fumarate and 0.1 to 0.5 percent of magnesium stearate.
In the technical scheme of the invention, the pramipexole sustained-release tablet is obtained by a powder direct compression method.
In the technical scheme of the invention, the direct powder compression method comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving;
step 2: uniformly mixing the pramipexole dihydrochloride obtained in the step 1, a flow aid, a slow-release material and a filling agent accounting for 15-35% of the total amount of the filling agent;
and step 3: adding the adhesive and the filler accounting for 15-35% of the total amount of the filler after the step 2 is finished, and uniformly mixing;
and 4, step 4: adding the rest filling agent after the step 3 is finished, and uniformly mixing;
and 5: adding a lubricant and mixing after the step 4 is finished to prepare an intermediate;
step 6: tabletting to obtain the final product.
In the prior art, a powder direct pressing process is adopted, so that the content difference among tablets is large, the content uniformity is difficult to ensure, the product release is fast, and the in-vivo release is difficult to control. The technology solves the problem of low uniformity of the sustained-release preparation in the prior art by adjusting and optimizing the proportion of the glidant and the lubricant and setting the combination proportion of the sustained-release matrix, delays the release rate of the medicament from the preparation form, reduces the absorption rate of the medicament by an organism, can keep a relatively stable blood concentration of the medicament in the body, continuously plays the medicament effect, reduces the administration frequency, stabilizes the treatment effect and is beneficial to improving the compliance of patients.
Advantageous effects
The sustained-release preparation can simultaneously realize the purposes of high uniformity and delayed release, and avoids the decomposition of the medicine by adopting a direct tabletting method.
Detailed Description
The reagents used in the examples are listed below:
mirapex ER commercial Boehringer Ingelheim (Boringer Invitrogen)
Pramipexole dihydrochloride: self-made
Lactose, microcrystalline cellulose 102, microcrystalline cellulose 112: FMC
Anhydrous calcium hydrogen phosphate, carbomer: BASF
Hypromellose K100M, hypromellose K4M: chemistry of Dow
Eudragit RD: winning wound
Sodium stearyl fumarate, glyceryl behenate: JRS
Magnesium stearate: shandong chat
For a further understanding of the present invention, reference will now be made in detail to the following examples.
Example 1: preparation of pramipexole dihydrochloride sustained-release tablets
Prescription: specification of 0.375mg, prescription amount of 2000 tablets
The preparation process comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% microcrystalline cellulose 102 and sodium stearyl fumarate for 5 min; sequentially adding Eudragit RD and hypromellose K100M, and mixing for 5 min;
and step 3: after the step 2 is finished, adding hydroxypropyl methylcellulose K4M and the rest 70% of microcrystalline cellulose, and mixing for 10 min;
and 4, step 4: adding anhydrous calcium hydrophosphate after the step 3 is finished, and mixing for 5 min;
and 5: adding magnesium stearate after the step 4 is finished, and mixing for 3min to obtain an intermediate;
step 6: tabletting
Example 2: preparation of pramipexole dihydrochloride sustained-release tablets
Prescription: specification of 0.375mg, prescription amount of 2000 tablets
The process comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% microcrystalline cellulose 112 and sodium hard fumarate for 5 min; sequentially adding Eudragit RD and hypromellose K100M, and mixing for 5 min;
and step 3: after the step 2 is finished, adding povidone K29/30 and the rest 70% of microcrystalline cellulose 112, and mixing for 10 min;
and 4, step 4: adding anhydrous calcium hydrophosphate after the step 3 is finished, and mixing for 5 min;
and 5: adding glyceryl behenate after the step 4 is finished, and mixing for 3min to obtain an intermediate;
step 6: tabletting
Example 3: preparation of pramipexole dihydrochloride sustained-release tablets
Prescription: specification 1.5mg, prescription amount 2000 tablets
The process comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% microcrystalline cellulose 102 and sodium stearyl fumarate for 5 min; sequentially adding Eudragit RD and hypromellose K100M, and mixing for 5 min;
and step 3: after the step 2 is finished, adding hydroxypropyl methylcellulose K4M and the rest 70% of microcrystalline cellulose 102, and mixing for 10 min;
and 4, step 4: adding anhydrous calcium hydrophosphate after the step 3 is finished, and mixing for 5 min;
and 5: adding magnesium stearate after the step 4 is finished, and mixing for 3min to obtain an intermediate;
step 6: tabletting
Example 4: preparation of pramipexole dihydrochloride sustained-release tablets
Prescription: specification of 0.75mg, prescription amount of 2000 tablets
The process comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% microcrystalline cellulose 102 and sodium stearyl fumarate for 5 min; sequentially adding Eudragit RD and hypromellose K100M, and mixing for 5 min;
and step 3: after the step 2 is finished, adding povidone K29/32 and the rest 70% of microcrystalline cellulose 102, and mixing for 10 min;
and 4, step 4: adding anhydrous calcium hydrophosphate after the step 3 is finished, and mixing for 5 min;
and 5: adding magnesium stearate after the step 4 is finished, and mixing for 3min to obtain an intermediate;
step 6: tabletting
Comparative example 5: prepared according to the original prescription composition
Prescription: specification of 0.375mg, prescription amount of 2000 tablets
Step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% microcrystalline cellulose 102 and superfine silica gel powder for 5 min; adding carbomer, and mixing for 5 min;
and step 3: adding the rest 70% of microcrystalline cellulose 102 after the step 2 is finished, and mixing for 10 min;
and 4, step 4: adding corn starch after the step 3 is finished, and mixing for 5 min;
and 5: adding magnesium stearate after the step 4 is finished, and mixing for 3min to obtain an intermediate;
step 6: tabletting
Comparative examples 6 to 14: prepared according to the compositions of formulas 6-14 in Table 1
The process comprises the following steps:
step 1: taking pramipexole dihydrochloride, and sieving the pramipexole dihydrochloride by a 80-mesh sieve
Step 2: mixing pramipexole dihydrochloride obtained in the step 1 with 30% of filling agent and flow aid for 5 min; sequentially adding the sustained-release matrix after completion, and mixing for 5 min;
and step 3: adding the adhesive and the rest 70% of the filler after the step 2 is finished, and mixing for 10 min;
and 4, step 4: adding a lubricant after the step 4 is finished, and mixing for 3min to obtain an intermediate;
and 5: and (6) tabletting.
As can be seen from the results in Table 2, the content uniformity values A +1.80S of examples 1, 2, 3 and 4 are all less than 2.5, and the results are significantly less than those of 404649 batches and 603801 batches commercially available products, which indicates that better content uniformity can be obtained by the inventive process compared to the original manufacturer, while the content uniformity value A +1.80S of comparative example 5 is significantly greater than those of examples 1, 2, 3 and 4, which indicates that the use of different excipients has a significant effect on the content uniformity.
Example 7: in vitro release assay
900ml of phosphate buffer solution with the pH value of 6.8 is taken as a release medium, and the samples are taken at the rotating speed of 50 r/min for 2h, 4h, 6h, 8h, 12h and 24h respectively. The results of the release (%) of the different prescribed drugs at different time points are shown in the following table:
the above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (10)
1. The pramipexole sustained-release tablet is prepared from the following components, wherein the sum of the components is 100%:
wherein the sustained-release matrix is a combination of Eudragit RD and hypromellose K100M, and the mass ratio of Eudragit RD to hypromellose K100M in the sustained-release matrix is 1.3-3: 1;
the ratio of glidant to lubricant is glidant: 0.5-10% of lubricant;
the pramipexole sustained-release tablet is obtained by a powder direct compression method.
2. The pramipexole sustained release tablet of claim 1, wherein the ratio of the glidant to the lubricant is: 0.6-8% of lubricant.
3. Pramipexole extended release tablets according to claim 1 or 2, wherein the filler is selected from one or more of microcrystalline cellulose, lactose, anhydrous dibasic calcium phosphate, corn starch.
4. The pramipexole extended release tablet of claim 3, wherein the microcrystalline cellulose is microcrystalline cellulose 102, microcrystalline cellulose 112, or a combination thereof.
5. Pramipexole extended release tablets according to claim 3, wherein the filler is selected from the group consisting of microcrystalline cellulose and anhydrous dibasic calcium phosphate.
6. Pramipexole extended release tablets according to claim 1 or 2, wherein the binder is selected from hypromellose K4M, povidone K29/32 or a combination thereof.
7. Pramipexole sustained release tablets according to claim 1 or 2, wherein the glidant is selected from sodium stearyl fumarate, talc, aerosil or a combination thereof.
8. Pramipexole extended release tablets according to claim 1 or 2, wherein the lubricant is selected from magnesium stearate, glyceryl behenate or a combination thereof.
9. The pramipexole sustained release tablet according to claim 1, which is prepared from the following components, wherein the sum of the components is 100%: 0.12 to 0.18 percent of pramipexole dihydrochloride, 3 to 36 percent of microcrystalline cellulose 10233 to 36 percent, 22 to 24 percent of anhydrous calcium hydrophosphate, 17 to 19 percent of Eudragit RD, 10 to 14 percent of hydroxypropyl methylcellulose K100M 10, 4 to 11 percent of hydroxypropyl methylcellulose K4M 9, 0.3 to 0.5 percent of sodium stearyl fumarate and 0.2 to 0.4 percent of magnesium stearate; alternatively, the first and second electrodes may be,
the pramipexole sustained-release tablet is prepared from the following components, and the sum of the components is 100%: 0.12 to 0.18 percent of pramipexole dihydrochloride, 11233 to 36 percent of microcrystalline cellulose, 22 to 24 percent of anhydrous calcium hydrophosphate, 20 to 22 percent of Eudragit RD, 6 to 8 percent of hydroxypropyl methylcellulose K100M 6, 0 to 12 percent of povidone K29/3210 percent, 0.4 to 0.6 percent of sodium stearyl fumarate and 0.7 to 0.9 percent of glyceryl behenate; alternatively, the first and second electrodes may be,
the pramipexole sustained-release tablet is prepared from the following components, and the sum of the components is 100%: 0.3 to 0.5 percent of pramipexole dihydrochloride, 3 to 36 percent of microcrystalline cellulose 10233 to 36 percent, 23 to 25 percent of anhydrous calcium hydrophosphate, 20 to 22 percent of Eudragit RD, 6 to 9 percent of hydroxypropyl methylcellulose K100M 6, 4 to 11 percent of hydroxypropyl methylcellulose K4M 9, 0.8 to 1.2 percent of talcum powder and 0.4 to 0.6 percent of magnesium stearate; alternatively, the first and second electrodes may be,
the pramipexole sustained-release tablet is prepared from the following components, and the sum of the components is 100%: 0.15 to 0.35 percent of pramipexole dihydrochloride, 10235 to 38 percent of microcrystalline cellulose, 17 to 19 percent of anhydrous calcium hydrophosphate, 16 to 20 percent of Eudragit RD, 12 to 15 percent of hydroxypropyl methylcellulose K100M 12, 0 to 12 percent of povidone K29/3210 percent, 1 to 3 percent of sodium stearyl fumarate and 0.1 to 0.5 percent of magnesium stearate.
10. The method for preparing pramipexole sustained release tablets according to any one of claims 1 to 9, which is prepared by a powder direct compression method, comprising the steps of:
step 1: taking pramipexole dihydrochloride, and sieving;
step 2: uniformly mixing the pramipexole dihydrochloride obtained in the step 1, a flow aid, a slow-release material and a filling agent accounting for 15-35% of the total amount of the filling agent;
and step 3: adding an adhesive and a filler accounting for 15-35% of the total amount of the filler after the step 2 is finished, and uniformly mixing;
and 4, step 4: adding the rest filling agent after the step 3 is finished, and uniformly mixing;
and 5: adding a lubricant and mixing after the step 4 is finished to prepare an intermediate;
step 6: tabletting to obtain the final product.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910497313.5A CN110227067B (en) | 2019-06-10 | 2019-06-10 | Pramipexole dihydrochloride sustained-release tablet and preparation method thereof |
| PCT/CN2019/101616 WO2020248361A1 (en) | 2019-06-10 | 2019-08-20 | Pramipexole dihydrochloride sustained release tablet and preparation method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910497313.5A CN110227067B (en) | 2019-06-10 | 2019-06-10 | Pramipexole dihydrochloride sustained-release tablet and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110227067A CN110227067A (en) | 2019-09-13 |
| CN110227067B true CN110227067B (en) | 2021-03-02 |
Family
ID=67858683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910497313.5A Active CN110227067B (en) | 2019-06-10 | 2019-06-10 | Pramipexole dihydrochloride sustained-release tablet and preparation method thereof |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN110227067B (en) |
| WO (1) | WO2020248361A1 (en) |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006046256A1 (en) * | 2004-10-27 | 2006-05-04 | Alembic Limited | Extended release formulation of pramipexole dihydrochloride |
| WO2013034173A1 (en) * | 2011-09-06 | 2013-03-14 | Synthon Bv | Pramipexole extended release tablets |
| CN104146979A (en) * | 2013-05-14 | 2014-11-19 | 上海星泰医药科技有限公司 | Pramipexole dihydrochloride sustained release tablet and preparation method thereof |
| CN103520128B (en) * | 2013-10-12 | 2018-08-21 | 石家庄杏林锐步医药科技股份有限公司 | A kind of sustained-release tablet of Pramipexole, preparation method and its usage |
| CN105456216B (en) * | 2014-08-18 | 2019-11-05 | 江苏神龙药业股份有限公司 | Pramipexole hydrochloride slow release tablet composition and preparation method thereof |
| CN106983728B (en) * | 2016-01-21 | 2021-03-02 | 北京北大维信生物科技有限公司 | Pramipexole sustained release tablet and preparation method thereof |
| CN107951853B (en) * | 2016-10-17 | 2022-04-08 | 海思科制药(眉山)有限公司 | Pramipexole dihydrochloride sustained-release pharmaceutical composition and preparation method thereof |
| CN108159007B (en) * | 2017-12-29 | 2021-04-16 | 成都百裕制药股份有限公司 | Pramipexole dihydrochloride sustained-release preparation and preparation method thereof |
-
2019
- 2019-06-10 CN CN201910497313.5A patent/CN110227067B/en active Active
- 2019-08-20 WO PCT/CN2019/101616 patent/WO2020248361A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| CN110227067A (en) | 2019-09-13 |
| WO2020248361A1 (en) | 2020-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106943355B (en) | Pharmaceutical composition | |
| US10441585B2 (en) | Formulations containing nalbuphine and uses thereof | |
| JP4656672B2 (en) | Method for producing intraoral rapidly disintegrating tablet containing imidafenacin as active ingredient | |
| WO2009096560A1 (en) | Orally rapidly disintegrating tablet comprising imidafenacin | |
| WO2004054574A1 (en) | Solid drug for oral use | |
| TWI606848B (en) | Combination drug comprising gemigliptin and metformin, and method for the preparation thereof | |
| JP7084955B2 (en) | Ceritinib preparation | |
| EP2867199B1 (en) | Stable compositions of fesoterodine | |
| WO2005120463A1 (en) | Rapidly disintegrating tablets of risperidone | |
| TWI784575B (en) | A compound pharmaceutical composition and preparation method thereof | |
| WO2006123213A1 (en) | Modified release formulations of gliclazide | |
| TW200808358A (en) | Galenical formulations of organic compounds | |
| RU2613192C1 (en) | Tablets of clozapine with sustained release | |
| JP2005537295A (en) | Method for producing bicifazine | |
| CN110227067B (en) | Pramipexole dihydrochloride sustained-release tablet and preparation method thereof | |
| TW202227071A (en) | Controlled release pharmaceutical compositions in a monolithic matrix tablet form comprising rebamipide and processes for preparing the same | |
| KR102409102B1 (en) | pharmaceutical composition | |
| CN113908153A (en) | Buvalracetam pharmaceutical composition, preparation method and application thereof | |
| EP1490034B1 (en) | Novel pharmaceutical compositions for antihistaminic-decongestant combination and method of making such compositions | |
| US10548848B2 (en) | Alogliptin formulation | |
| WO2022036506A1 (en) | Composition and use of sglt-2 inhibitor and angiotensin receptor blockers | |
| WO2005016315A1 (en) | Pharmaceutical compositions of nateglinide and a high amount of a water-soluble filler | |
| US20070249694A1 (en) | Metaxalone formulations and methods for the preparation thereof | |
| JP6731136B2 (en) | Pharmaceutical formulation | |
| KR20160141045A (en) | Pharmaceutical composition containing of Bosentan |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |