A kind of itopride hydrochloride pharmaceutical composition

Abstract

The present invention relates to an itopride hydrochloride pharmaceutical composition, belonging to the technical field of pharmaceutical preparations. The technical solution of the present invention is: an itopride hydrochloride pharmaceutical composition, each tablet containing 50 mg of itopride hydrochloride, 25-45 mg of polyoxyl 40 stearate, 20-30 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate. The present invention provides an itopride hydrochloride pharmaceutical composition having a good mouthfeel, rapid dispersion, and a dissolution profile similar to that of the original formulation, and a preparation method.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and in particular relates to an itopride hydrochloride pharmaceutical composition. Background Art

[0002] Itopride hydrochloride has dopamine D2 receptor antagonist activity and acetylcholinesterase inhibitory activity, which synergistically exert gastrointestinal prokinetic effects. It is mainly used clinically for indigestion symptoms caused by slowed gastrointestinal motility (such as functional dyspepsia, chronic gastritis, etc.).

[0003] The original trade name of itopride hydrochloride tablets is Weilisu, with a specification of 50mg. The manufacturer is Abbott Japan Co., Ltd., Katsuyama Plant. Currently, the main dosage forms available in China include tablets, capsules and granules.

[0004] Research has revealed that the original itopride hydrochloride tablets are dissolving tablets, while ZL20151065606.2 proposes a 24-hour sustained-release tablet. Both can only be taken with warm water and cannot be dissolved in warm water, making them unsuitable for people with dysphagia or other ailments. ZL201210086799.1 mentions an itopride hydrochloride dispersible tablet, but the API in these tablets has not undergone any taste-masking treatment. Dissolving these tablets in warm water results in an extremely bitter taste, resulting in a poor user experience. Furthermore, the dissolution profile of these tablets is faster than that of the original formulation. Summary of the Invention

[0005] The purpose of the present invention is to provide an itopride hydrochloride pharmaceutical composition which has a good taste, can be quickly dispersed and has a dissolution curve similar to that of the original formulation and a preparation method thereof.

[0006] The invention adopts modern pharmaceutical preparation technology, prepares micropills from itopride hydrochloride, low-substituted hydroxypropyl cellulose, alginate and polyoxyl 40 stearate, and then mixes and tablets with microcrystalline cellulose, mannitol, cross-linked polyvinylpyrrolidone and magnesium stearate after drying.

[0007] The applicant found that after itopride hydrochloride was prepared into micropellets with low-substituted hydroxypropyl cellulose, alginate, and polyoxyl 40 stearate, the rapid dissolution of itopride hydrochloride in water was avoided; after the dried micropellets were mixed with microcrystalline cellulose, mannitol, cross-linked polyvinylpyrrolidone, and magnesium stearate and tableted, the rapid disintegration of the tablets in water was ensured.

[0008] The technical solution of the present invention is: an itopride hydrochloride pharmaceutical composition, characterized in that each tablet contains 50 mg of itopride hydrochloride, 25-45 mg of polyoxyl 40 stearate, 20-30 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate.

[0009] Preferably, the itopride hydrochloride pharmaceutical composition of the present invention is characterized in that each tablet contains 50 mg of itopride hydrochloride, 35 mg of polyoxyl 40 stearate, 25 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate.

[0010] The preparation method of the composition of the present invention comprises the following steps:

[0011] Step 1: Weigh the prescribed amount of polyoxyl 40 stearate, add 40-50℃ water to dissolve and set aside;

[0012] Step 2: Weigh the prescribed amount of itopride hydrochloride, low-substituted hydroxypropyl cellulose, and alginate, put them into a wet granulator and mix them thoroughly;

[0013] Step 3: Add the polyoxyl 40 stearate solution to the mixed material in the second step to prepare a soft material;

[0014] Step 4: Prepare pellets using an extrusion spheronizer with a 0.2 mm aperture screen;

[0015] Step 5: After the extruded pellets are dried in a fluidized bed, the undersize fraction is removed using a 0.1 mm pore size sieve.

[0016] Step 6: Mix the sieved pellets with microcrystalline cellulose, mannitol, crospovidone and magnesium stearate for tableting.

[0017] The beneficial effects of the present invention are:

[0018] Through pharmaceutical means, a new itopride hydrochloride pharmaceutical composition and preparation method were innovated, which effectively covered up the disadvantage of itopride hydrochloride's poor taste when it comes into contact with water, while ensuring the rapid disintegration of the tablets and the dissolution curve is similar to that of the reference preparation, thereby improving the compliance of patients with dysphagia. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below through specific embodiments, but this should not be construed as limiting the scope of the present invention to the following examples. Various substitutions or modifications made according to common technical knowledge and customary means in the art without departing from the above-mentioned method concept of the present invention are intended to be included within the scope of the present invention.

[0020] Example 1:

[0021]

[0022] Prepare 1000 tablets according to the preparation method described in the technical solution. Example

[0023]

[0024] Prepare 1000 tablets according to the preparation method described in the technical solution.

[0025] Example 3:

[0026]

[0027] Prepare 1000 tablets according to the preparation method described in the technical solution.

[0028] Comparative Example 1:

[0029]

[0030] Prepare 1000 tablets according to the following preparation method:

[0031] Step 1: Weigh the prescribed amount of itopride hydrochloride, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, and mannitol and mix them evenly in a wet granulator;

[0032] Step 2: Add appropriate amount of purified water to the above mixture for wet granulation;

[0033] Step 3: Transfer the wet material to a fluidized bed for drying and granulate using a 0.5 mm pore size sieve;

[0034] Step 4: Transfer the granulated material to the main mixing barrel, add cross-linked polyvinylpyrrolidone and mix for 10 minutes, then add magnesium stearate and mix for 5 minutes, and press into tablets.

[0035] Comparative Example 2:

[0036]

[0037] Prepare 1000 tablets according to the preparation method described in the technical solution.

[0038] Comparative Example 3:

[0039]

[0040] Prepare 1000 tablets according to the preparation method described in the technical solution.

[0041] Test Example 1 Taste Test:

[0042] The samples of Examples 1-3 and Comparative Examples 1-2 were dispersed in 37°C warm water, and 10 people tasted and scored them one by one, with 10 points being the best and 1 point being the worst. The specific results are as follows:

[0043]

[0044] It can be seen from the scores in the above table that the use of alginate and polyoxyl 40 stearate for micropellet granulation can well mask the bitter taste of the itopride hydrochloride raw material, while the taste of Comparative Example 1 is extremely poor because the raw material is directly dissolved in water.

[0045] Test Example 2 Disintegration Time Investigation:

[0046] Referring to the relevant provisions of the 2020 edition of the Chinese Pharmacopoeia, Part IV 0921 Disintegration Time Inspection Method, the disintegration time of Examples 1-3 and Comparative Examples 1-3 was investigated, and the specific results are as follows:

[0047]

[0048] From the disintegration time data in the above table, it can be seen that Examples 1-3 and Comparative Examples 1-3 can all disintegrate quickly.

[0049] Referring to the relevant provisions of Part IV 0931 Dissolution and Release Determination Method of the 2020 edition of the Chinese Pharmacopoeia, pH 1.2 was used as the dissolution medium, the volume was 900 mL, the paddle method was used, and the rotation speed was 50 rpm per minute. The dissolution amounts of the products of Examples 1-3 and Comparative Examples 1-3 were measured at 5 min, 10 min, 15 min, and 20 min, respectively. The dissolution similarity factor f2 with the original formulation was calculated. The specific results are as follows:

[0050]

[0051] Note: When f2≥50, the dissolution curves are judged to be similar.

[0052] As can be seen from the dissolution curve data in the above table, the dissolution amount of Comparative Example 1, which was not granulated with micropellets, was greater than 85% in 10 minutes, which was significantly faster than the original formulation. When the amount of alginate and polyoxyl 40 stearate was within the patent protection range, the dissolution curves of Examples 1-3 were similar to those of the original formulation. Conversely, the dissolution curves of Comparative Examples 2-3 were not similar to those of the original formulation.

Claims

1. A pharmaceutical composition of itopride hydrochloride, characterized in that Each tablet contains 50 mg of itopride hydrochloride, 25-45 mg of polyoxyl 40 stearate, 20-30 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate. Itopride hydrochloride, low-substituted hydroxypropyl cellulose, alginate, and polyoxyl 40 stearate are made into micropills, which are then dried and compressed into tablets with the remaining excipients.

2. The itopride hydrochloride pharmaceutical composition according to claim 1, characterized in that Each tablet contains 50 mg of itopride hydrochloride, 35 mg of polyoxyl 40 stearate, 25 mg of alginate, 10 mg of low-substituted hydroxypropyl cellulose, 20 mg of microcrystalline cellulose, 30 mg of mannitol, 6 mg of cross-linked polyvinylpyrrolidone, and 1 mg of magnesium stearate.

3. The method for preparing the itopride hydrochloride pharmaceutical composition according to claim 1, wherein: The following steps are involved: Step 1: Weigh the prescribed amount of polyoxyl 40 stearate, add 40-50℃ water to dissolve and set aside; Step 2: Weigh the prescribed amount of itopride hydrochloride, low-substituted hydroxypropyl cellulose, and alginate, put them into a wet granulator and mix them thoroughly; Step 3: Add the polyoxyl 40 stearate solution to the mixed material in the second step to prepare a soft material; Step 4: Prepare pellets using an extrusion spheronizer with a 0.2 mm aperture screen; Step 5: After the extruded pellets are dried in a fluidized bed, the undersize fraction is removed using a 0.1 mm pore size sieve. Step 6: Mix the sieved pellets with microcrystalline cellulose, mannitol, crospovidone and magnesium stearate for tableting.

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