CN111514111A - Pharmaceutical composition containing mosapride citrate and preparation method thereof - Google Patents
Pharmaceutical composition containing mosapride citrate and preparation method thereof Download PDFInfo
- Publication number
- CN111514111A CN111514111A CN202010375279.7A CN202010375279A CN111514111A CN 111514111 A CN111514111 A CN 111514111A CN 202010375279 A CN202010375279 A CN 202010375279A CN 111514111 A CN111514111 A CN 111514111A
- Authority
- CN
- China
- Prior art keywords
- mosapride citrate
- low
- water
- mosapride
- soluble starch
- 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.)
- Pending
Links
Classifications
-
- 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
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a pharmaceutical composition containing mosapride citrate and a preparation method thereof. The pharmaceutical composition provided by the invention is prepared by suspending and dispersing mosapride citrate and low-substituted hydroxypropyl cellulose in a water-soluble starch solution, performing spray drying, mixing with pharmaceutically acceptable auxiliary materials, and tabletting. The prepared tablet has the advantages of good dissolution rate, high stability and the like.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a pharmaceutical composition containing mosapride citrate and a preparation method thereof.
Background
Mosapride citrate is a gut prokinetic agent and is a selective 5-hydroxytryptamine 4(5-HT4) receptor agonist. The action principle of the compound stimulates cholinergic interneurons of the gastrointestinal tract and 5-HT4 receptors of the internus musculus plexus to promote the release of acetylcholine, thereby enhancing the gastrointestinal motility.
Mosapride citrate tablet is a digestive tract prokinetic agent developed by Sumitomo pharmaceutical corporation, first sold in Japan in 1998 and sold under the trade name of
The dosage forms on the market comprise tablets and granules. In 2000, Mosapride citrate tablet and granule approved by Sumitomo corporation of Japan and imported into China, with trade name of
To date, mosapride citrate is mainly marketed in several countries of asia and south america, and has become one of the main drugs recommended by experts in chronic gastric diseases in china to treat gastrointestinal tract disorders accompanied by chronic gastric diseases. In 2006, the granular approval article number of Sumitomo cancelled and no longer appeared on the market in China, and only the tablet on the market in China currently has the specification of 5mg (calculated by anhydrous Mosapride citrate).
The domestic imitation drugs or new drug types comprise tablets, capsules, dispersible tablets, granules, orally disintegrating tablets, dripping pills, oral solutions and the like.
Mosapride citrate is white or off-white crystalline powder, its chemical name is 4-amino-5-chloro-2-ethoxy-N- { [4- (4-fluorobenzyl) -2-morpholinyl ] methyl } benzamide citric acid dihydrate, and its structural formula is as follows:
the molecular formula is as follows: c21H25ClFN3O3·C6H8O7·2H2O
Molecular weight: 650.05
Mosapride citrate is a BCS II drug, a low-solubility drug. Therefore, the fast and slow dissolution rate of the medicinal components in the preparation is only key to the influence of high and low bioavailability of the medicament in vivo. According to research, the existing tablet containing the 4-amino-5-chloro-2-ethoxy-N- { [4- (4-fluorobenzyl) -2-morpholinyl ] methyl } benzamide citric acid dihydrate composition on the market at home is low in dissolution prevalence (less than 60% in 45 min) in a buffer salt medium with pH 6.8. Meanwhile, related substances are remarkably increased in the process of investigating the stability of the preparation, and the stability of the preparation is poor.
CN101816639B discloses a tablet containing mosapride citrate and a preparation method thereof, the method comprises the steps of adding mosapride citrate into absolute ethyl alcohol, heating in water bath at 60-65 ℃ until the mosapride citrate is completely dissolved, adding a water-soluble carrier material, stirring to dissolve the water-soluble carrier material, transferring the solution into a rotary evaporator, evaporating the ethanol under reduced pressure at 60 ℃ to prepare a solid dispersion, and further processing the solid dispersion into the tablet, wherein the process is complex.
CN101273973B discloses a pharmaceutical composition containing mosapride citrate prepared by directly tabletting powder and a preparation method thereof. The tablets prepared by the patent technology can be quickly disintegrated, but for insoluble medicines, the medicines can not be dissolved in a dissolving medium after being quickly disintegrated.
CN104188927A discloses a mosapride citrate tablet and a preparation method thereof, the method comprises dissolving citric acid in ethanol, adding mosapride citrate raw material, stirring to dissolve, drying the solution to obtain a mixture; then mixing the mixture with pharmaceutically acceptable adjuvants, and tabletting. The patent technology adopts citric acid as a solubilizer, but the citric acid has low melting point, is easy to stick and wash in the tabletting process, and increases the difficulty of process preparation.
Disclosure of Invention
Aiming at the defects of the prior invention, the invention aims to provide a preparation composition which has simple, convenient and feasible process and meets the requirements on dissolution rate and stability.
Through a large amount of researches, the following results are found: when the mosapride citrate is fully contacted with the low-substituted hydroxypropyl cellulose, the solubility of the mosapride citrate in a buffer salt medium with the pH value of 6.8 can be obviously improved. And the mosapride citrate and the low-substituted hydroxypropyl cellulose are dispersed and suspended in a water-soluble starch solution for spray drying, and the obtained particles can obtain higher solubility level in a buffer salt medium with pH 6.8.
And further mixing the granules obtained by spray drying with pharmaceutically acceptable auxiliary materials, and tabletting to obtain the mosapride citrate tablet with high dissolution and stable related substances.
The invention is realized by the following technology:
a mosapride citrate tablet is prepared by the following method: dispersing low-substituted hydroxypropyl cellulose in water-soluble starch solution, adding mosapride citrate, stirring to fully disperse to obtain mosapride citrate, low-substituted hydroxypropyl cellulose and water-soluble starch suspension. Spray drying the suspension to obtain granule containing medicine. Then mixing the drug-containing granules with pharmaceutically acceptable auxiliary materials, and tabletting.
In some embodiments, in the above mosapride citrate tablet, the weight ratio of mosapride citrate to low-substituted hydroxypropylcellulose is 1: 0.5-6, preferably 1: 2-3.5.
In some embodiments, in the above mosapride citrate tablet, the weight ratio of the mosapride citrate to the water-soluble starch is 1: 0.2-3, preferably 1: 0.3-1.
Specifically, in some embodiments, the mosapride citrate tablet or a subset thereof, wherein the pharmaceutically acceptable excipient is any one or a combination of a filler, a disintegrant, and a lubricant; more specifically, the other pharmaceutically acceptable adjuvants comprise a filler, preferably lactose or corn starch, a disintegrating agent, preferably croscarmellose sodium, and a lubricant, preferably magnesium stearate.
In some embodiments, the present invention provides a mosapride citrate tablet, wherein the mosapride citrate has a particle size of D90＜60μm。
In some preferred embodiments of the present invention, the preparation of the mosapride citrate tablet comprises the following steps: dispersing low-substituted hydroxypropyl cellulose in water-soluble starch solution at 40-60 deg.C, adding mosapride citrate, stirring for more than 10min to disperse completely to obtain mosapride citrate, low-substituted hydroxypropyl cellulose and water-soluble starch suspension; spray drying the suspension to obtain granule containing medicine. More preferably, the medicine-containing particles are characterized in that the weight percentage of the material of the particles distributed on a 60-80 mesh screen is not less than 80%.
Compared with the prior art, the invention has simple preparation process, rapid drug dissolution and stable related substances of the tablet, and is suitable for industrial production.
Detailed Description
The following examples further illustrate the benefits of the present invention, and are intended to be illustrative only and not limiting as to the scope of the invention, and variations and modifications apparent to those of ordinary skill in the art in light of the teachings herein are also included within the scope of the invention.
The formulation composition for each example is as follows:
watch 1
Examples 1-4 were prepared in the following manner:
weighing the low-substituted hydroxypropyl cellulose with the prescription amount, fully stirring and dispersing the low-substituted hydroxypropyl cellulose into the water-soluble starch solution prepared according to the prescription amount, and continuously stirring and dispersing the mosapride citrate with the prescription amount into the suspension to obtain suspension of the three. And carrying out fluidized bed spray drying on the obtained suspension to prepare the granules containing the mosapride citrate. Mixing the granules with lactose, corn starch and croscarmellose sodium, adding magnesium stearate, mixing, and tabletting.
Comparative example 1 was prepared in the following manner:
the mosapride citrate, low-substituted hydroxypropyl cellulose, lactose and corn starch are premixed in a high-speed mixing wet granulator for 10min, and then water-soluble starch aqueous solution adhesive is used for pulp granulation. The soft material is wet-granulated with a 20-mesh sieve and then dried with a fluidized bed. Sieving the obtained granule with 16 mesh sieve, adding croscarmellose sodium, premixing for 5min, adding magnesium stearate, mixing for 3min, and tabletting.
Comparative example 2 was prepared in the following manner:
weighing the low-substituted hydroxypropyl cellulose with the prescription amount, fully stirring and dispersing the low-substituted hydroxypropyl cellulose in a hydroxypropyl cellulose solution prepared according to the prescription amount, and continuously stirring and dispersing the mosapride citrate with the prescription amount in the suspension to obtain suspension of the three. And carrying out fluidized bed spray drying on the obtained suspension to prepare the granules containing the mosapride citrate. Mixing the granules with lactose, corn starch and croscarmellose sodium, adding magnesium stearate, mixing, and tabletting. In the embodiment, the suspension of the obtained mosapride citrate, low-substituted hydroxypropyl cellulose and hydroxypropyl cellulose has poor dispersion state, a spray gun is easily blocked in the process, the fluctuation of the particle state is large after spray drying, and the granulation effect is poor.
The research of the invention finds that the high proportion of the low-substituted hydroxypropyl cellulose in the formula affects the feasibility of preparation operation and is not beneficial to the smooth implementation of the process. When the weight ratio of the mosapride citrate to the low-substituted hydroxypropyl cellulose in the formula is higher than 1:6, the dispersion state of the suspension of the mosapride citrate, the low-substituted hydroxypropyl cellulose and the water-soluble starch is poor, the operation feasibility is influenced to a certain extent, and the preparation requirement of the process can be still met. But the feasibility of the preparation operation is obviously reduced along with the increase of the dosage of the low-substituted hydroxypropyl cellulose, which is not beneficial to the preparation of the preparation. On the other hand, too high a proportion of water-soluble starch in the formulation also has an effect on the operational feasibility. When the weight ratio of the mosapride citrate to the water-soluble starch in the formula is higher than 1:3, the obtained mosapride citrate, low-substituted hydroxypropyl cellulose and water-soluble starch suspension is large in medicine-containing granules after spray drying, and hard in granule pieces, so that the preparation is not facilitated.
Verification examples
And (3) dissolution measurement: taking the tablet samples of the above examples, according to a dissolution determination method (second method of appendix XC of second part of 2010 edition of Chinese pharmacopoeia), taking 900ml of phosphate buffer (pH6.8) as a dissolution medium, rotating at 50 revolutions per minute, operating according to the method, and respectively sampling and determining the dissolution rate at 45 min.
The results of the measurements are given in the following table:
watch two
| 45min dissolution (%) | |
| Example 1 | 90.6％(88.5％、92.2％、89.6％、90.7％、90.6％、91.9％) |
| Example 2 | 98.3％(98.6％、99.4％、94.2％、100.1％、98.9％、98.6％) |
| Example 3 | 94.7％(95.1％、91.7％、96.2％、97.9％、93.9％、93.1％) |
| Example 4 | 90.4％(89.9％、88.5％、93.3％、86.8％、90.9％、92.8％) |
| Comparative example 1 | 61.3％(61.7％、59.9％、62.8％、58.6％、61.9％、62.7％) |
| Comparative example 2 | 72.3％(83.0％、85.5％、81.7％、79.8％、83.4％、80.1％) |
In the above results, in examples 1 to 4, when the tablet is prepared by using the technology of the present invention, the dissolution rate can reach more than 90% in 45min, and the dissolution rate is high. However, in comparative example 1 (prepared by a conventional process), the dissolution rate is only 61% at 45min, and the dissolution rate is very low. In comparative example 2, although mosapride citrate and low-substituted hydroxypropylcellulose are also adopted to be suspended in advance and then spray-dried to form granules, the dispersion solution is replaced by the hydroxypropylcellulose solution, and the preparation process finds that the dispersion state of the spray suspension is poor, the feasibility of the preparation process is poor, and the dissolution degree of the corresponding tablet is only 72 percent, which is inferior to that of examples 1 and 2, but is obviously higher than that of comparative example 1. The technology of the invention is shown as follows: the mosapride citrate and the low-substituted hydroxypropyl cellulose are jointly suspended in the water-soluble starch solution, and the spray drying process has stable preparation process and good feasibility, and can obviously improve the dissolution of the tablet.
The above-mentioned embodiments are merely exemplary embodiments for fully illustrating the present invention, and the scope of the present invention is not limited to the above-mentioned embodiments, but defined by the contents of the claims. All matters disclosed in the specification including the abstract and all methods and steps disclosed herein may be combined in any combination, except combinations where the features and/or steps are mutually exclusive. Each feature disclosed in this specification, including the abstract, can be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. Those skilled in the art should also make equivalents and modifications to the present invention without departing from the spirit and scope of the present invention. Such modifications are also within the scope of the present invention. Each reference cited in this application is incorporated herein in its entirety.
Claims (10)
1. The mosapride citrate tablet is characterized by being prepared by the following method: dispersing low-substituted hydroxypropyl cellulose in a water-soluble starch solution, adding mosapride citrate, and stirring to fully disperse to obtain mosapride citrate, low-substituted hydroxypropyl cellulose and water-soluble starch suspension; spray drying the suspension to obtain granule containing medicine, mixing the granule containing medicine with other pharmaceutically acceptable adjuvants, and tabletting.
2. The mosapride citrate tablet of claim 1, wherein the weight ratio of the mosapride citrate to the low-substituted hydroxypropylcellulose is 1: 0.5-6.
3. The mosapride citrate tablet according to claim 2, wherein the weight ratio of the mosapride citrate to the low-substituted hydroxypropylcellulose is preferably 1:2 to 3.5.
4. The mosapride citrate tablet according to claim 1, wherein the weight ratio of the mosapride citrate to the water-soluble starch in the mosapride citrate tablet is 1: 0.2-3.
5. The mosapride citrate tablet according to claim 4, wherein the weight ratio of the mosapride citrate to the water-soluble starch is preferably 1: 0.3-1.
6. The mosapride citrate tablet according to any one of claims 1-5, wherein the other pharmaceutically acceptable excipients are selected from any one or a combination of fillers, disintegrants, lubricants.
7. The mosapride citrate tablet according to any one of claims 1-5, wherein the other pharmaceutically acceptable excipients comprise a filler, preferably lactose or corn starch, a disintegrant, preferably croscarmellose sodium, and a lubricant, preferably magnesium stearate.
8. The mosapride citrate tablet of claim 1, wherein the mosapride citrate has a particle size of D90＜60μm。
9. The mosapride citrate tablet of claim 1, prepared by a process comprising: dispersing low-substituted hydroxypropyl cellulose in water-soluble starch solution at 40-60 deg.C, adding mosapride citrate, stirring for more than 10min to disperse completely to obtain mosapride citrate, low-substituted hydroxypropyl cellulose and water-soluble starch suspension; spray drying the suspension to obtain granule containing medicine.
10. The mosapride citrate tablet of claim 9, wherein the particles are distributed on a 60-80 mesh screen at a material weight ratio of not less than 80%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010375279.7A CN111514111A (en) | 2020-05-07 | 2020-05-07 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010375279.7A CN111514111A (en) | 2020-05-07 | 2020-05-07 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111514111A true CN111514111A (en) | 2020-08-11 |
Family
ID=71906923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010375279.7A Pending CN111514111A (en) | 2020-05-07 | 2020-05-07 | Pharmaceutical composition containing mosapride citrate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111514111A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN101816639A (en) * | 2010-01-15 | 2010-09-01 | 鲁南制药集团股份有限公司 | Tablets of mosapride citrate and preparation method thereof |
| CN104606139A (en) * | 2014-05-16 | 2015-05-13 | 沈阳药科大学 | Preparation and application of drug powder |
| CN105560249A (en) * | 2014-10-10 | 2016-05-11 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing mosapride citrate |
| CN107744509A (en) * | 2017-10-24 | 2018-03-02 | 浙江昂利康制药股份有限公司 | Mosapride Citrate Tablets agent and preparation method thereof |
-
2020
- 2020-05-07 CN CN202010375279.7A patent/CN111514111A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN101816639A (en) * | 2010-01-15 | 2010-09-01 | 鲁南制药集团股份有限公司 | Tablets of mosapride citrate and preparation method thereof |
| CN104606139A (en) * | 2014-05-16 | 2015-05-13 | 沈阳药科大学 | Preparation and application of drug powder |
| CN105560249A (en) * | 2014-10-10 | 2016-05-11 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing mosapride citrate |
| CN107744509A (en) * | 2017-10-24 | 2018-03-02 | 浙江昂利康制药股份有限公司 | Mosapride Citrate Tablets agent and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11413295B2 (en) | Oral preparation of obeticholic acid | |
| JP5401327B2 (en) | Tablets with improved dissolution | |
| RU2466717C2 (en) | Pharmaceutical solid preparation containing benzazepin and method for preparing it | |
| CN105287411A (en) | Perampanel dispersible tablet and preparation method thereof | |
| CN104644575B (en) | A kind of roflumilast dispersible tablet composition and preparation method thereof | |
| CN109875972B (en) | Olmesartan medoxomil and amlodipine pharmaceutical composition | |
| CN112315918B (en) | Ticagrelor pharmaceutical preparation | |
| CN117442577B (en) | Candesartan cilexetil microchip and preparation method and application thereof | |
| CN107334772B (en) | Antiretroviral pharmaceutical composition | |
| US20120010216A1 (en) | Pharmaceutical compositions containing vanoxerine | |
| CN103893138A (en) | Tablet containing linezolid crystal form III | |
| JP2020518611A (en) | Compositions with improved water solubility and bioavailability | |
| CN111888477B (en) | Bedaquinoline pharmaceutical preparation | |
| CN111514111A (en) | Pharmaceutical composition containing mosapride citrate and preparation method thereof | |
| CN107913254A (en) | A kind of ticagrelor dispersible tablet and preparation method thereof | |
| CN106265559B (en) | Olanzapine oral disnitegration tablet and preparation method thereof | |
| WO2022042646A1 (en) | Lurasidone hydrochloride composition and preparation method therefor | |
| CN104000821B (en) | Oral double-layer tablet containing telmisartan and amlodipine besylate and preparation method thereof | |
| CN108926541A (en) | Ziprasidone oral disintegrating tablet and preparation method thereof | |
| CN115105504A (en) | Brexpiprazole orally disintegrating tablet and preparation method thereof | |
| CN116370423A (en) | Ticagrelor orally disintegrating tablet and preparation method thereof | |
| WO2021185006A1 (en) | Lenvatinib pharmaceutical composition, preparation method therefor and application thereof | |
| CN106539807B (en) | Stable pharmaceutical composition and preparation method thereof | |
| CN104000788A (en) | Emtricitabine-containing tablet and preparation method thereof | |
| JP6558530B2 (en) | Aripiprazole pharmaceutical formulation |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200811 |
|
| RJ01 | Rejection of invention patent application after publication |