CN110934853A - Mosapride citrate sustained-release pellet capsule and preparation method thereof - Google Patents
Mosapride citrate sustained-release pellet capsule and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a mosapride citrate sustained-release pellet capsule and a preparation process thereof, belonging to the field of pharmaceutical preparations, wherein the sustained-release pellet capsule consists of a drug-containing pellet core and a sustained-release coating layer, wherein the pellet core contains mosapride citrate, a filling agent, an adhesive, a disintegrating agent and a sustained-release framework material; the slow release coating layer contains Eudragit NE30D, polyvidone K30 and talcum powder. The mosapride citrate sustained-release pellet capsule prepared by the invention consists of a plurality of small unit pellets, is a framework type and membrane control type dual-combined sustained-release capsule, and has better sustained-release effect. The burst release danger possibly occurring in the common preparation is improved, the preparation process is simple, the technical difficulty is low, the difference between batches is small, the reproducibility of a release curve is good, and the preparation method is suitable for large-scale production.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and provides a mosapride citrate sustained-release pellet capsule and a preparation method thereof.
Background
Mosapride citrate, (+/-) 4-amino-5-chloro-2-ethoxy-N- { [4- (4-fluorobenzyl) -2-morpholinyl ] methyl } benzamide citrate dihydrate, is a 3 rd generation prokinetic drug, is a potent and selective 5-HT4 receptor agonist, stimulates acetylcholine release through a 5-HT4 receptor exciting the internus plexus, enhances gastric and duodenal motility, has no effect on the small intestine and colon, and does not affect gastric acid secretion.
Mosapride citrate is very soluble in glacial acetic acid, slightly soluble in ethanol, and practically insoluble in water or chloroform. The traditional Chinese medicine composition is a common preparation in tablets and capsules at present, and is mainly used for treating chronic gastritis, functional dyspepsia, diabetic gastroparesis caused by gastroesophageal reflux disease and gastric dysfunction of patients with partial gastrectomy.
According to pharmacokinetic research, the mosapride citrate tablet or capsule has a half-life period of 2h in vivo, needs to be taken 3 times a day, has large blood concentration fluctuation, and is prepared into a multi-unit sustained-release capsule.
The sustained-release preparation is a preparation which can slowly release the medicine in the body after being taken so that the medicine can maintain effective blood concentration for a long time. The sustained-release preparation can reduce the fluctuation of the blood concentration of the medicine in vivo, reduce the times of taking the medicine, reduce the adverse reaction and increase the compliance of patients. The multi-unit sustained-release preparation represented by the pellet has more advantages in the aspect of curative effect. According to different drug release mechanisms and structures, the sustained-release pellets comprise skeleton sustained-release pellets, film-controlled sustained-release pellets and skeleton and film-controlled combined sustained-release pellets. The multi-unit pellet sustained release preparation can overcome the performance difference generated by the gastrointestinal tract transfer time and irregular gastric emptying difference, can be dispersed into a plurality of small units in the gastrointestinal tract, has good drug release uniformity, improves the contact time between the drug and the gastrointestinal tract, improves the bioavailability and reduces the stimulation to the gastrointestinal tract mucous membrane.
The slow release pellets are filled into capsules, which belongs to a multi-unit slow release preparation, avoids the burst release effect of single-unit slow release preparation, reduces the toxicity and side effect of the medicine, and ensures the safety of clinical medication.
At present, sustained-release pellets are most commonly prepared into capsules, and the preparation process is simple and the technical difficulty is low. Therefore, the mosapride citrate is prepared into sustained-release pellets with certain release characteristics and then is filled into capsules.
The mosapride citrate is prepared into the multi-unit sustained-release pellet capsule, can continuously exert curative effect for a long time, has small adverse reaction and large market potential, and can obtain certain economic and social benefits.
Disclosure of Invention
In order to solve the defects of the prior art, the invention aims to provide a novel sustained-release drug delivery system, namely a mosapride citrate sustained-release pellet capsule and a preparation method thereof.
The sustained-release pellet capsule of the invention achieves sustained-release effect mainly through two modes of framework type and membrane control type. The burst release danger possibly occurring in the common dosage form is improved, the influence of a single pellet on the release behavior of the preparation is reduced, the phenomenon of overhigh local drug concentration is prevented, the fluctuation of the blood drug peak concentration in vivo is reduced, the effective blood drug concentration can be maintained for a long time, the contact between the drug and the gastrointestinal tract is improved, the absorption of the drug is facilitated, the bioavailability is improved, and the like.
Specifically, the invention is realized by the following steps:
a Mosapride citrate sustained-release pellet capsule comprises 80-95% of a drug-containing pellet core and 5.0-20% of a sustained-release coating layer, wherein the drug-containing pellet core is composed of Mosapride citrate, a filling agent, an adhesive, a disintegrating agent and a sustained-release framework material; the slow release coating layer consists of Eudragit NE30D, polyvidone K30, talcum powder and water.
Further, the slow release pellet capsule of mosapride citrate comprises the following components in percentage by mass:
pill core prescription:
the slow-release coating layer formula comprises:
furthermore, the prescription comprises the following components in percentage by mass:
pill core prescription:
the slow-release coating layer formula comprises:
the slow release matrix material of the invention comprises one or more of HPMC, Eudragit NE30D, Eudragit RL-PO and Eudragit RS-PO. The slow release matrix material is selected from a mixture of HPMC and Eudragit NE30D, and the weight ratio of HPMC to Eudragit is: NE30D in a ratio of 2-3:1-2, preferably HPMC: the proportion of Eudragit NE30D was 2.5: 1.5. By the preferred ratio, the rate of drug release is significantly increased.
Further, in the formula of the slow release coating layer, talcum powder is used as an anti-sticking agent, povidone K30 is used as a pore-forming agent, and Eudragit NE30D is used as a slow release coating material. The Eudragit NE30D has good plasticity and ductility, is easy to form a film, does not need to add a plasticizer, is an aqueous dispersion coating solution, is superior to a film formed by the conventional organic solvent coating solution, reduces energy consumption, saves production cost and is beneficial to safe production and environmental protection in the coating process.
The coating weight is 5-15% of the pellet core, preferably 15% of the pellet core.
The filler is selected from one or more of microcrystalline cellulose, silicified microcrystalline cellulose, starch, pre-crosslinked starch, lactose, sucrose, mannitol, sorbitol and dextrin, and preferably one or more of microcrystalline cellulose, lactose and pre-crosslinked starch.
The binder is selected from one or more of polyvinylpyrrolidone (PVP K30) aqueous solution, hypromellose (HPMC E5) or hydroxypropyl cellulose (HPC) aqueous solution. Preferably hypromellose.
The disintegrant comprises dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose (L-HPC), crosslinked polyethylene pyrrolidone and crosslinked sodium carboxymethyl cellulose. Preferably low-substituted hydroxypropyl cellulose and croscarmellose sodium, wherein the mass ratio of the two is 1: 1.
The invention also provides a preparation method of the sustained-release pellet capsule, which comprises the following steps:
(1) the mosapride citrate raw material is micronized.
(2) Uniformly mixing the mosapride citrate, the filler, the disintegrant, the slow-release framework material and the like, and adding the adhesive to prepare a soft material.
(3) Preparing pellets by using an extrusion spheronizer: setting the aperture of a screen mesh to be 0.8mm, the extrusion speed to be 15-30 rpm, the spheronization speed to be 1000-1500 pm, and the spheronization time to be 1-4 min, and screening micro-pills of 20-40 meshes to obtain the mosapride citrate drug-containing micro-pills;
(5) fluidized bed drying: setting the drying temperature to be 60 ℃, and drying for 20-25 minutes;
(6) coating: preparing a coating solution according to a formula of a slow-release coating layer by using a high-shear dispersion emulsifying machine, filtering by using a 60-mesh sieve, and coating slow-release coating by using a fluidized bed;
(7) the prepared sustained-release pellets are filled into hard capsules.
Furthermore, the preparation method comprises the following steps:
(1) the mosapride citrate raw material is micronized and has the particle size D90≤30μm。
(2) Uniformly mixing the mosapride citrate, the filler, the disintegrant, the sustained-release framework material and the like, and adding a proper amount of an ethanol solution of hydroxypropyl methylcellulose to prepare a soft material.
(3) Extruding and rounding to prepare the pellet. The aperture of the sieve mesh is 0.8mm, the extrusion speed is 15-30 rpm, the rolling speed is 1000-1500 pm, and the rolling time is 1-4 min. Sieving to obtain 20-40 mesh micro-pill to obtain mosapride citrate micro-pill.
(5) And (4) drying by a fluidized bed, setting the drying temperature to be 60 ℃, and drying for 20-25 minutes.
(6) Coating: preparing coating solution according to the formula of the slow-release coating layer by using a high-shear dispersion emulsifying machine, filtering by using a 60-mesh sieve, and coating the slow-release coating by using a fluidized bed. The temperature of the material is kept between 23 and 28 ℃, and the atomization pressure is generally between 0.1 and 0.2 MPa.
(7) The prepared sustained-release pellets are filled into hard capsules.
Compared with the prior art, the invention has the advantages that:
the mosapride citrate sustained-release pellet capsule prepared by the invention consists of a plurality of small unit pellets, is a framework type and membrane control type dual-combined sustained-release capsule, and has better sustained-release effect. Improves the burst release danger possibly occurring in the common preparation, reduces the fluctuation of the blood concentration in vivo, can continuously exert the curative effect for a long time, and improves the bioavailability. The sustained-release pellet capsule is convenient for patients to carry and take, and increases the compliance of patients in taking medicine. The preparation process is simple, the technical difficulty is low, the difference between batches is small, the reproducibility of a release curve is good, and the preparation method is suitable for large-scale production.
Description of the drawings:
FIG. 1: cumulative in vitro release of examples 1-4;
FIG. 2: cumulative in vitro release of examples 5-9;
FIG. 3: cumulative in vitro release of examples 10-14;
FIG. 4: cumulative in vitro release of examples 15-19;
FIG. 5: cumulative in vitro release of examples 2, 4, 20, 21;
in the figure, the abscissa represents time (h), and the ordinate represents cumulative dissolution (%);
FIG. 6: a flow chart of a preparation process of the mosapride citrate sustained-release capsule.
Detailed Description
Example 1: mosapride citrate sustained-release pellet capsule and preparation process thereof
The mosapride citrate raw material is micronized and has the particle size D90Less than or equal to 30 mu m. Weighing 10g of mosapride citrate, 46g of microcrystalline cellulose, 2g of low-substituted hydroxypropyl methylcellulose and 40g of HPMC (hydroxy propyl methyl cellulose), uniformly mixing, and adding1.0 percent of hydroxypropyl methylcellulose and 30 percent of ethanol solution are properly prepared into soft materials. And (4) extruding the soft material into a spheronizer to prepare the pellets. The aperture of the sieve mesh is set to be 0.8mm, the extrusion speed is 18rpm, the rounding speed is 1000pm, and the rounding time is 2 min. Sieving, and taking pellets of 20-40 meshes. And (4) drying by a fluidized bed, setting the drying temperature to be 60 ℃, and drying for 20-25 minutes. The fluidized bed is coated with a slow-release coating film, the temperature of the materials is kept at 23-28 ℃, the atomization pressure is generally 0.1-0.2MPa, the weight of the coating is increased by 10%, and the prepared pellets are filled into hard capsules.
Wherein the formula of the slow-release coating layer is as follows:
example 2: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
other auxiliary materials and the dosage and the preparation process are the same as those of the example 1.
Example 3: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
other auxiliary materials and the dosage and the preparation process are the same as those of the example 1.
Example 4: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
other auxiliary materials and the dosage and the preparation process are the same as those of the example 1.
Example 5: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
the slow release matrix material consists of HPMC and Eudragit NE30D in the weight ratio of 1 to 1, and other auxiliary materials, the use amount and the preparation process are the same as those in the embodiment 1.
Example 6: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
the slow release matrix material consists of HPMC and Eudragit NE30D in a weight ratio of 3:1, and other auxiliary materials, the use amount and the preparation process are the same as those in the embodiment 1.
Example 7: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
the slow release matrix material consists of HPMC and Eudragit NE30D in a weight ratio of 5:3, and other auxiliary materials, the use amount and the preparation process are the same as those in the embodiment 1.
Example 8: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
the slow release matrix material consists of HPMC and Eudragit NE30D in a weight ratio of 6:1, and other auxiliary materials, the use amount and the preparation process are the same as those in the embodiment 1.
Example 9: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
the slow release matrix material consists of HPMC and Eudragit NE30D in the weight ratio of 1 to 2, and other auxiliary materials, the use amount and the preparation process are the same as those in the embodiment 1.
Example 10: mosapride citrate sustained-release pellet capsule and preparation process thereof
The formula of the pill core is the same as that of the example 3, and the preparation process is the same as that of the example 1.
The slow-release coating layer formula comprises:
example 11: mosapride citrate sustained-release pellet capsule and preparation process thereof
The formula of the pill core is the same as that of the example 3, and the preparation process is the same as that of the example 1.
The slow-release coating layer formula comprises:
example 12: mosapride citrate sustained-release pellet capsule and preparation process thereof
The formula of the pill core is the same as that of the example 3, and the preparation process is the same as that of the example 1.
The slow-release coating layer formula comprises:
example 13: mosapride citrate sustained-release pellet capsule and preparation process thereof
The formula of the pill core is the same as that of the example 3, and the preparation process is the same as that of the example 1.
The slow-release coating layer formula comprises:
example 14: mosapride citrate sustained-release pellet capsule and preparation process thereof
The formula of the pill core is the same as that of the example 3, and the preparation process is the same as that of the example 1.
The slow-release coating layer formula comprises:
example 15: mosapride citrate sustained-release pellet capsule and preparation process thereof
The mosapride citrate raw material is micronized and has the particle size D90Less than or equal to 30 mu m. Weighing 10g of mosapride citrate, 47g of microcrystalline cellulose, 2g of low-substituted hydroxypropyl methylcellulose and 40g of HPMC, uniformly mixing, and adding a proper amount of 1.0% of hydroxypropyl methylcellulose and 30% of ethanol solution to prepare a soft material. And (4) extruding the soft material into a spheronizer to prepare the pellets. The aperture of the sieve mesh is set to be 0.8mm, the extrusion speed is 18rpm, the rounding speed is 1000pm, and the rounding time is 2 min. Sieving, and taking pellets of 20-40 meshes. And (4) drying by a fluidized bed, setting the drying temperature to be 60 ℃, and drying for 20-25 minutes. The fluidized bed is coated with a slow-release coating film, the temperature of the materials is kept at 23-28 ℃, the atomization pressure is generally 0.1-0.2MPa, the weight of the coating is increased by 3%, and the prepared pellets are filled into hard capsules.
Wherein the formula of the slow-release coating layer is as follows:
example 16: mosapride citrate sustained-release pellet capsule and preparation process thereof
The weight gain of the coating was 5%, and the pellets were filled into hard capsules, the other procedures being the same as in example 15.
Example 17: mosapride citrate sustained-release pellet capsule and preparation process thereof
The weight gain of the coating was 10%, and the pellets were filled into hard capsules, the other procedures being the same as in example 15.
Example 18: mosapride citrate sustained-release pellet capsule and preparation process thereof
The weight gain of the coating was 15%, and the pellets were filled into hard capsules, the other procedures being the same as in example 15.
Example 19: mosapride citrate sustained-release pellet capsule and preparation process thereof
The coating weight gain was 20%, and the pellets were filled into hard capsules, otherwise the same as in example 15.
Example 20: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
other auxiliary materials and the dosage and the preparation process are the same as those of the example 1.
Example 21: mosapride citrate sustained-release pellet capsule and preparation process thereof
Pill core prescription:
other auxiliary materials and the amount and the preparation process are the same as those of the example 1
Verification of the examples:
1. determination of the degree of Release
The release rate is determined by a dissolution and release rate measuring method (first method of 0931 in the four general rules of the chinese pharmacopoeia 2015 edition). Octadecylsilane chemically bonded silica is used as a filler for chromatographic conditions and system applicability tests; dissolving citrate solution (sodium citrate 8.82g, adding water 800ml for dissolving, adjusting pH to 4.0 with dilute hydrochloric acid, adding water to 1000ml) -acetonitrile (70:30) as mobile phase, detecting wavelength of 274nm, and theoretical plate number not less than 2000 calculated according to Mosapride peak. Taking 900ml of 0.1mol/L hydrochloric acid solution as a dissolution medium, operating at a rotating speed of 50 revolutions per minute, taking a proper amount of solution after setting out for 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours, centrifuging, and taking supernatant as a test solution; and timely supplementing the dissolution medium with the same temperature and volume; taking a proper amount of mosapride citrate as a reference substance, precisely weighing, adding acetonitrile-water to dissolve and quantitatively dilute into a solution of 0.28mg/ml, precisely weighing 1ml, putting into a 50ml measuring flask, diluting a dissolution medium to a scale, and shaking up to obtain a reference substance solution. Precisely measuring the sample solution and the reference solution by 50 μ l each, injecting into a liquid chromatograph, recording chromatogram, and calculating the cumulative release degree of each capsule by peak area according to external standard method.
TABLE 1 cumulative in vitro Release degree of examples 1-4
As can be seen from Table 1, the release effect of the examples 1-3 in the dosage range of the invention is better, the release can be smooth, the requirements of 80% of pharmacopoeia can be met, and the drug release phenomenon can be smooth. Too much matrix is used in example 4, which may hinder the release of the active agent.
TABLE 2 cumulative in vitro Release of examples 5-9
As can be seen from Table 2, the final dissolution effect through the cumulative release of the preferred matrix material examples 5-7 is better than the effect of using only one matrix material, and it can be further shown that the selection of the matrix material of the present invention is somewhat inventive.
TABLE 3 cumulative in vitro Release of examples 10-14
As can be seen from Table 3, the dissolution and the stability of drug release of the mosapride citrate can be obviously improved by the optimized coating material and proportion.
TABLE 4 cumulative in vitro Release of examples 15-19
As can be seen from Table 4, the drug release rate and the final dissolution rate are different for different coating weight percentages, and it can be seen from the table that the drug release and dissolution effects are the best when the coating content is 5-15%, the release is not uniform when the coating content is 3%, which brings a certain safety hazard to clinical medication, and the dissolution of mosapride citrate is affected when the coating content is 20%.
TABLE 5 cumulative in vitro Release of examples 1-4
As can be seen from Table 5, the combination of different disintegrants was selected to have a better effect than the single disintegrant, on the basis of achieving the same effect.
2. Reproducibility of the process
Three consecutive batches of sustained-release pellet capsules were prepared according to the recipe and process of example 7, and the process reproducibility and the uniformity of in vitro release were examined. According to the in vitro release result, the three batches of samples are uniformly and stably released in vitro, so that the slow release effect is achieved. Fitting the in vitro release of the mosapride citrate sustained-release pellet capsule, and taking a zero-order release model: Mt/M∞K t, first order release model: Mt/M∞＝1-e-kt, Higuchi release model: Mt/M∞＝k t1/2And (6) fitting. Mosapride citrate tablet sustained-release pelletThe external drug release is closer to the first-order drug release, and the release of the mosapride citrate is probably the result of the synergistic action of diffusion and skeleton erosion. Because the slow release mechanism of the slow release preparation is complex and comprises diffusion, erosion, dissolution, combination of diffusion and erosion dissolution and the like, the release process is difficult to accurately guess by using a fitting equation for simulation, and the process may involve the combined action of several models.
TABLE 5 in vitro cumulative Release assay results
TABLE 6 fitting of in vitro Release equation of Mosapride citrate tablet sustained-Release pellet Capsule
Claims (10)
1. A Mosapride citrate sustained-release pellet capsule is characterized in that the sustained-release pellet capsule consists of 80-95% of a drug-containing pellet core and 5.0-20% of a sustained-release coating layer, wherein the pellet core contains Mosapride citrate, a filling agent, an adhesive, a disintegrating agent and a sustained-release framework material; the sustained release coating layer comprises Eudragit NE30D, polyvidone K30, talcum powder and water.
2. The sustained-release pellet capsule according to claim 1, wherein the formulation comprises the following components in percentage by mass: pill core prescription:
the slow-release coating layer formula comprises:
3. the sustained-release pellet capsule according to claim 2, wherein the formulation comprises the following components in percentage by mass: pill core prescription:
the slow-release coating layer formula comprises:
4. the extended release pellet capsule of claim 1, wherein said extended release matrix material comprises one or more of HPMC, Eudragit NE30D, Eudragit RL-PO and Eudragit RS-PO.
5. The sustained-release pellet capsule according to claim 4, wherein the sustained-release matrix material is selected from a mixture of HPMC and Eudragit NE30D, and the weight ratio of HPMC: the proportion of Eudragit NE30D is 2-3:1-2, preferably HPMC: the proportion of Eudragit NE30D was 2.5: 1.5.
6. The extended release pellet capsule of claim 1, wherein the weight of the coating is 5-15% of the pellet core, preferably 10% of the pellet core.
7. The extended release pellet capsule of claim 1, wherein said filler is selected from one or more of microcrystalline cellulose, silicified microcrystalline cellulose, starch, pre-crosslinked starch, lactose, sucrose, mannitol, sorbitol, dextrin, preferably one or more of microcrystalline cellulose, lactose, pre-crosslinked starch.
8. The sustained-release pellet capsule according to claim 1, wherein the binder is one or more selected from polyvinylpyrrolidone, hydroxypropylmethylcellulose, or hydroxypropylcellulose.
9. The sustained-release pellet capsule according to claim 1, wherein the disintegrant is one or more selected from the group consisting of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, and croscarmellose sodium.
10. A method of preparing an extended release pellet capsule as claimed in any one of claims 1 to 9, comprising the steps of:
(1) the mosapride citrate raw material is micronized.
(2) Uniformly mixing the mosapride citrate, the filler, the disintegrant, the slow-release framework material and the like, and adding the adhesive to prepare a soft material.
(3) Preparing pellets by using an extrusion spheronizer: extruding at 15-30 rpm, rolling at 1000-1500 pm for 1-4 min, and sieving to obtain 20-40 mesh micro-pellets to obtain Mosapride citrate drug-containing micro-pellets;
(5) fluidized bed drying: setting the drying temperature to be 60 ℃, and drying for 20-25 minutes;
(6) coating: preparing a coating solution according to a formula of a slow-release coating layer by using a high-shear dispersion emulsifying machine, and performing slow-release coating by using a fluidized bed;
(7) the prepared sustained-release pellets are filled into hard capsules.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143886A (en) * | 2021-05-07 | 2021-07-23 | 苏州康恒研新药物技术有限公司 | Preparation method of vortioxetine hydrobromide pellet sustained-release preparation |
| CN113181140A (en) * | 2021-05-07 | 2021-07-30 | 苏州康恒研新药物技术有限公司 | Ticagrelor skeleton sustained-release pellet and preparation method thereof |
| CN114425046A (en) * | 2021-12-16 | 2022-05-03 | 南通联亚药业有限公司 | Diltiazem hydrochloride sustained-release capsule |
| CN114557980A (en) * | 2022-03-22 | 2022-05-31 | 郑州市中医院（郑州市红十字医院） | Calcitriol sustained-release pellet and preparation method thereof |
| CN115844856A (en) * | 2023-01-06 | 2023-03-28 | 北京中科利华医药研究院有限公司 | Bicyclol solid preparation and preparation method thereof |
| CN116725985A (en) * | 2023-06-02 | 2023-09-12 | 石家庄四药有限公司 | Micropill combined urapidil sustained-release capsule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071374A2 (en) * | 2003-02-11 | 2004-08-26 | Torrent Pharmaceuticals Limited | Once a day orally administered pharmaceutical compositions |
| CN101987091A (en) * | 2009-08-07 | 2011-03-23 | 北京天衡药物研究院 | Venlafaxine hydrochloride sustained-release pellet capsules |
| US20160030436A1 (en) * | 2013-03-15 | 2016-02-04 | Korea United Pharm. Inc. | Mosapride sustained-release formulation providing pharmacological and clinical effects with once-daily administration |
| CN109010319A (en) * | 2018-08-22 | 2018-12-18 | 重庆医药高等专科学校 | A kind of preparation method of mosapride citrate gastric floating slow-release pellet |
-
2019
- 2019-12-30 CN CN201911388110.9A patent/CN110934853B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071374A2 (en) * | 2003-02-11 | 2004-08-26 | Torrent Pharmaceuticals Limited | Once a day orally administered pharmaceutical compositions |
| CN101987091A (en) * | 2009-08-07 | 2011-03-23 | 北京天衡药物研究院 | Venlafaxine hydrochloride sustained-release pellet capsules |
| US20160030436A1 (en) * | 2013-03-15 | 2016-02-04 | Korea United Pharm. Inc. | Mosapride sustained-release formulation providing pharmacological and clinical effects with once-daily administration |
| CN109010319A (en) * | 2018-08-22 | 2018-12-18 | 重庆医药高等专科学校 | A kind of preparation method of mosapride citrate gastric floating slow-release pellet |
Non-Patent Citations (2)
| Title |
|---|
| 何艳 等: "缓控释微丸的研究概况", 《解放军药学学报》, vol. 28, no. 3, pages 267 - 270 * |
| 李欣 等: "挤出滚圆法制备枸橼酸莫沙必利骨架缓释微丸", 《解放军药学学报》, vol. 26, no. 1, pages 4 - 6 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113143886A (en) * | 2021-05-07 | 2021-07-23 | 苏州康恒研新药物技术有限公司 | Preparation method of vortioxetine hydrobromide pellet sustained-release preparation |
| CN113181140A (en) * | 2021-05-07 | 2021-07-30 | 苏州康恒研新药物技术有限公司 | Ticagrelor skeleton sustained-release pellet and preparation method thereof |
| CN114425046A (en) * | 2021-12-16 | 2022-05-03 | 南通联亚药业有限公司 | Diltiazem hydrochloride sustained-release capsule |
| CN114425046B (en) * | 2021-12-16 | 2023-10-20 | 南通联亚药业股份有限公司 | Diltiazem hydrochloride sustained-release capsule |
| CN114557980A (en) * | 2022-03-22 | 2022-05-31 | 郑州市中医院（郑州市红十字医院） | Calcitriol sustained-release pellet and preparation method thereof |
| CN115844856A (en) * | 2023-01-06 | 2023-03-28 | 北京中科利华医药研究院有限公司 | Bicyclol solid preparation and preparation method thereof |
| CN116725985A (en) * | 2023-06-02 | 2023-09-12 | 石家庄四药有限公司 | Micropill combined urapidil sustained-release capsule and preparation method thereof |
| CN116725985B (en) * | 2023-06-02 | 2024-03-05 | 石家庄四药有限公司 | Micropill combined urapidil sustained-release capsule and preparation method thereof |
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