JP2011126857A - Paroxetine hydrochloride-containing tablet for oral use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a paroxetine hydrochloride-containing tablet for oral use which is miniaturized, in which discoloration is inhibited, and which is excellent in content uniformity. <P>SOLUTION: The paroxetine hydrochloride-containing tablet for oral use is characterized in that when granulating a formulation containing paroxetine hydrochloride by a wet granulation method, water is used for a solvent to be used, and the mass per one tablet is lessened. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a paroxetine hydrochloride-containing oral tablet that is miniaturized and prevented from discoloration and excellent in content uniformity.

うつ病・うつ状態，パニック障害に効能，効果を有する薬物として世界中の多くの国で販売されている。Paroxetine has the following formula:

It is marketed in many countries around the world as a drug that is effective and effective in depression, depression, and panic disorder.

Currently, as a tablet containing paroxetine hydrochloride, a trade name Paxil ^RTM tablet (produced by GlaxoSmithKline Co., Ltd.) containing 10 mg or 20 mg of paroxetine per tablet is commercially available. A tablet containing 10 mg of paroxetine has a total amount of 178 mg, a diameter of 6.6 mm, a thickness of 3.6 mm, and a tablet containing 20 mg has a total amount of 357 mg, each having a diameter of 8.1 mm and a thickness of 4.8 mm. However, it is larger as a tablet than the content of active ingredients. For this reason, it is desirable to reduce the overall mass to make the tablets smaller and to be easily taken.

  In addition, formulations containing paroxetine hydrochloride are often found to turn pink.

Patent Document 1 discloses that tableting is performed using a prescription / production method that does not include water as a method for preventing discoloration. Specifically, dry direct compression of paroxetine hydrochloride or paroxetine hydrochloride is disclosed. After dry granulation, it is compressed into tablets. However, the dry direct tableting method generally has a drawback that segregation between the pharmacologically active ingredient and other excipients tends to occur, and the content of the pharmacologically active ingredient in the tablet tends to vary. In addition, paroxetine hydrochloride has the property of being hardly soluble in water, and in order to ensure appropriate solubility, it is necessary to devise measures such as reducing the particle size. In order to ensure fluidity, it is necessary to select one having a large particle size. Therefore, the difference in particle size and apparent specific gravity between paroxetine hydrochloride particles and excipient particles may be a factor, and there may be a problem that segregation between paroxetine hydrochloride particles and excipient tends to occur in the tableting process. .
On the other hand, the method of compressing paroxetine hydrochloride into tablets after dry granulation is considered to be a method that takes into account the above-mentioned uniformity of content, but in general, after dry granulation, crushing using a pulverizer is performed. A process and a sizing process using a sieve are required, and the process becomes complicated. In addition, there are drawbacks such as tablet hardness being lowered in the tableting process.
When reducing the mass per tablet and reducing the size of the tablet, this itself impairs the moldability such as tableting properties, tablet hardness, and the release of active ingredients from the obtained tablets. Therefore, any of the above methods is unsuitable as a manufacturing method for reducing the size of the tablet while maintaining the content uniformity.
In Patent Document 2, as a method for preventing discoloration, when a preparation containing paroxetine hydrochloride is produced by wet granulation, it is tableted using ethanol or a mixed solvent of ethanol and water as a solvent. It is disclosed.
However, the use of organic solvents in the work process has many problems such as adverse health effects on workers, environmental pollution, and residual in the preparation. Moreover, the mass of the uncoated tablet described in the Examples is 320 mg or 350 mg per tablet, and although there is no description regarding the size, it is difficult to say that it is a miniaturized tablet.

  Japanese Patent No. 3037757   JP 2007-186450 A

  An object of the present invention is to provide an oral tablet containing paroxetine hydrochloride that is miniaturized and prevented from discoloration and excellent in content uniformity.

In order to solve the above-mentioned problems, the present inventors diligently studied the problems inherent in the prior art. Surprisingly, in the wet granulation method, by using only water as a solvent, tablets 1 It was found that even when the mass per tablet was reduced, discoloration during manufacture and after formulation could be prevented, and tablets with good paroxetine hydrochloride content uniformity in the formulation could be obtained.
The tablet is smaller than the conventional product and improved in dosage, exhibits the same dissolution properties as the conventional product, and does not cause any problems in tablet moldability and tablet hardness.

That is, the present invention
(1) A paroxetine hydrochloride-containing oral tablet characterized by being produced by a wet granulation method using only water as a solvent,
(2) The paroxetine hydrochloride-containing oral tablet according to (1), wherein the wet granulation method is a stirring granulation method,
(3) The paroxetine hydrochloride-containing oral tablet according to (1) or (2), wherein the mass per uncoated tablet is 16 parts by mass or less per 1 part by mass of paroxetine,
(4) The paroxetine according to any one of (1) to (3), wherein the mass per uncoated tablet is 100 to 160 mg in the case of a 10 mg tablet, and 200 to 320 mg in the case of a 20 mg tablet Oral tablets containing hydrochloride,
(5) Paroxetine hydrochloride-containing oral administration according to (1) to (3), wherein the mass per uncoated tablet is 130 mg for a 10 mg tablet and 260 mg for a 20 mg tablet Tablets,
About.

  The oral tablet containing paroxetine hydrochloride of the present invention is miniaturized while having the same amount of paroxetine as the conventional preparation, has sufficient hardness as a practical tablet, and has excellent dissolution properties. Compared with paroxetine tablets, it is easy to take. Furthermore, since the oral tablet containing paroxetine hydrochloride of the present invention does not use an organic solvent in the production process, it also has the advantage that it does not cause problems such as adverse health effects on workers, environmental pollution, and residue in the preparation. .

The result of the dissolution test of Test Example 4 is shown.

Hereinafter, the present invention will be further described in detail.
In the oral tablet containing paroxetine hydrochloride of the present invention (hereinafter also referred to as the paroxetine tablet of the present invention or the tablet of the present invention), the active ingredient paroxetine ((-)-(3S, 4R) -4- (4-fluorphenyl). ) -3-[(3,4-methylenedioxy) phenoxymethyl] piperidine) uses paroxetine which is usually used in medicine.
Paroxetine used in the present invention is a pharmaceutically acceptable salt, that is, an acid addition salt, and paroxetine hydrochloride is particularly preferable. In addition, although paroxetine hydrochloride is known in the form of an anhydride or hemihydrate, it is preferable to use paroxetine hydrochloride in the form of hemihydrate in the present invention.

The wet granulation method in the present invention is a method in which only water is used as a solvent and a powder obtained by mixing paroxetine hydrochloride and other pharmaceutical additives is granulated by a batch addition or spraying operation. , Kneading granulation method, extrusion granulation method, stirring granulation method, fluidized bed granulation method. In the tablet of the present invention, the stirring granulation method is particularly preferable.
The paroxetine tablet of the present invention is 1 as an uncoated tablet in terms of the balance between moldability such as tableting property, tablet hardness, release of active ingredients from the obtained tablet, and tablet size. The mass per tablet is 10 to 16 parts by mass with respect to 1 part by mass of paroxetine. Specifically, in the case of a tablet having a content of 10 mg, it is preferably 100 to 160 mg, particularly preferably 130 mg, and in the case of a 20 mg tablet, it is preferably 200 mg to 320 mg, particularly preferably 260 mg.

In the tablet of the present invention, the pharmaceutical additive mixed with paroxetine hydrochloride is not particularly limited, and can be formulated according to the purpose, for example, excipient, disintegrant, binder, lubricant. Agents, coloring agents, sweeteners, surfactants and the like.
Examples of excipients include lactose, D-mannitol, starches such as corn starch, celluloses such as crystalline cellulose, and calcium hydrogen phosphate. In the tablet of the present invention, calcium hydrogen phosphate is preferably used as an excipient, and the range of 85 to 92.5% is preferable based on the mass per uncoated tablet.
Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, low-substituted hydroxypropylcellulose, and crospovidone. In the tablet of the present invention, it is preferable to use sodium carboxymethyl starch as a disintegrant, and the range of 0.5 to 2.5% is preferable based on the mass per uncoated tablet.
Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, and the like. These binders can be mixed with paroxetine hydrochloride and placed in the granulator, or dissolved in water and added, but not necessary.
After the granulation powder obtained by the wet granulation method is mixed with a lubricant, it can be made into a tablet form using a tableting machine.
As a lubricant. Examples include magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester.
Moreover, it can be in the form of a powder or fine granule without being mixed with a lubricant, and can also be made into a capsule by filling a hard capsule. In the tablet of the present invention, magnesium stearate is preferably used as a lubricant, and the range of 0.5 to 1.5% is preferable based on the mass per uncoated tablet.
The tablet may be in the form of an uncoated tablet as it is, or may be formed into a film-coated tablet by coating an appropriate film layer on the tablet surface. Usually, the paroxetine tablet of the present invention is preferably a film-coated tablet. The coating protects the tablet from light discoloration and decomposition of the drug substance, conceals the taste of the drug, and prevents paroxetine from being decomposed by gastric acid before reaching the absorption site of the small intestine.
Film coating usually uses a coating pan used for tablet coating, and specifically, a coated tablet can be produced using a high coater (trade name), a doria coater (trade name), or the like.
Although the component used for a coating layer is not specifically limited, It is preferable to consist of a composition containing the water-soluble high molecular compound which can form a film.
Examples of the water-soluble polymer compound include polyvinyl pyrrolidone, polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, hydroxyethyl cellulose, and hypromellose, among which hypromellose is preferable. In order to prevent discoloration due to light and the like, decomposition of the drug substance, and the like, an opacifying agent and a coloring agent may be included in the coating agent, and it is preferable to include these in the present invention. The content ratio of the film forming component to the total coating component (solid component) is preferably in the range of 50 to 80%.

In film coating, in addition to the film-forming agent, other components may be added as necessary for the purpose of imparting flexibility to the film or performing shading or coloring to prevent discoloration due to light or the like. You may add in a film coating agent. Examples of the other components include plasticizers such as polyethylene glycol (for example, polyethylene glycol 6000), triethyl citrate, diethyl phthalate, propylene glycol, glycerin, dibutyl phthalate, opacifying agents (for example, titanium oxide), colorants ( For example, iron sesquioxide, tar dye) and the like can be mentioned. Any of them may be used within a range that achieves the purpose according to the purpose. The composition ratio of the plasticizer, the opacifying agent and the colorant to the total amount of the coating component is not particularly limited. For example, the opacifying agent is in the range of 10 to 30% with respect to the total amount of the coating component (solid component), and the colorant is 0.01 A range of ˜0.05% is preferred.
The amount of the coating component (solid component) used in the coating agent of the paroxetine tablet of the present invention is in the range of about 2 to 5%, preferably in the range of 3 to 4%, based on the total amount of the plain tablet.

The method for producing the paroxetine tablet of the present invention will be specifically described below.
The paroxetine tablet of the present invention is prepared by wet granulating a tableting powder containing paroxetine, an excipient, a disintegrant and the like using a granulator, preferably a stirring granulator using only water as a solvent, and adjusting the size as necessary. In addition, it is mixed with a lubricant to obtain a tableted powder, and then tableted to obtain an uncoated tablet. If necessary, the uncoated tablet can be coated to form a coated tablet.
The tableting powder used for the production of the paroxetine tablet of the present invention is prepared by mixing paroxetine, excipients and disintegrants and other pharmaceutical additives (for example, binders, etc.) as necessary by conventional methods. It can be obtained by granulating with a granulator and, if necessary, preparing into a tableting powder. As the granulation method, agitation granulation is preferable because the number of working steps is relatively small and the conditions can be easily set, and a granulated product having excellent fluidity and compression moldability can be obtained in a short process.
For example, after uniformly mixing paroxetine, calcium hydrogen phosphate as an excipient, and other additives (excluding lubricants) as necessary, use a granulator etc. with water alone as the solvent. The granule can be obtained by granulating and drying. As the granulator at this time, it is preferable to use an agitation granulator because granulation is performed by a wet granulation method in which heavy calcium hydrogen phosphate is a main content component and only water is added as appropriate. The above drying may be performed by a granulator or a shelf dryer, and the drying time varies depending on conditions such as the drying temperature. is there. As a measure of drying, it is preferable to dry until the water content of granules obtained by granulation becomes 0.4 to 1.0%.
Granules obtained by stirring granulation are usually preferably sized, and granulated products or sized granules obtained by stirring granulation are preferably used as sodium carboxymethyl starch as a disintegrant and A powder for tableting is prepared by adding magnesium stearate as a lubricant and mixing uniformly.

  The paroxetine tablet (plain tablet) of the present invention is produced by tableting the tableting powder obtained in this manner by a conventional method. The tableting conditions in the tableting process are not particularly limited as long as the target tablets can be obtained. Usually, the tableting pressure of uncoated tablets is about 9 to 15 KN.

The tablet (plain tablet) of the present invention obtained above can be used as the tablet of the present invention by appropriately coating the tablet (for example, film coating) as necessary.
The film coating can be performed by a conventional method. For example, the coating components (preferably water-soluble polymers, opacifying agents such as titanium oxide and plasticizers such as polyethylene glycol) and water and / or ordinary organic solvents such as alcohol (methyl alcohol, ethyl alcohol, isopropyl alcohol) Etc.), ketones (eg, acetone, ethyl methyl ketone, etc.), chlorinated hydrocarbons (eg, methylene chloride, dichloroethane, etc.), etc. (preferably water or a mixture of water and a C2-C4 alcohol such as ethyl alcohol, more preferably Is coated with the liquid for coating liquid (coating liquid) on the paroxetine uncoated tablet of the present invention using an appropriate coating apparatus, and then dried to obtain the film-coated tablet of the present invention. be able to. At this time, the coated tablet can be dried by a conventional method.
The obtained coated tablets may be polished (glazed) as desired. For polishing, a polishing wax such as carnauba wax may be added by a conventional method to polish the film-coated tablet.
Through the above steps, a coated paroxetine tablet of the present invention can be obtained.

  As for the paroxetine tablet of this invention obtained by making it above, the mass per tablet as an uncoated tablet is 10-16 mass parts with respect to 1 mass part of paroxetine. Therefore, when producing tablets with a conventional paroxetine content of 10 mg mass / tablet, the mass per uncoated tablet can be about 100 to 160 mg, preferably about 130 mg, and the paroxetine content When manufacturing tablets with a mass of 20 mg / tablet, the mass per uncoated tablet can be 200 mg to 320 mg, preferably about 260 mg, so that the conventional paroxetine tablets can be further downsized. it can. For example, in the case of a tablet of 10 mg mass / tablet, when the thickness of the uncoated tablet is about 2.5 to 3.0 mm, preferably about 2.7 mm, the uncoated tablet diameter is 5.5 to 6.5 mm. In the case of a tablet with 20 mg mass / tablet, when the thickness of the uncoated tablet is about 3.5 to 4.5 mm, preferably about 4.0 mm, The tablet diameter can be about 7.0-8.0 mm, preferably about 7.5 mm. Even if the uncoated tablets are coated at about 5 to 10 mg / tablet, the thickness and diameter of the coated tablets obtained are increased by about 0.1 mm compared to the uncoated tablets. Compared to this, the size can be reduced.

  Table 1 below shows preferred composition examples of the paroxetine tablet of the present invention. The content ratio is the content ratio (mass) with respect to the whole uncoated tablet. A preferred tablet of the present invention contains the following components within the following composition range, and the total is adjusted to 100%.

  In addition, when the tablet of this invention is a film coating tablet, the usage-amount of the coating component total amount with respect to an uncoated tablet is about 1 to 10%, Preferably it is about 2 to 5%.

The paroxetine tablet of the present invention obtained as described above is smaller than conventional products and has improved dosing properties.
In addition, discoloration during manufacture and after formulation is prevented, and when stored in an open state at 40 ° C. and 75% relative humidity, it is a conventional product that is thought to have been produced by the conventional dry direct compression method. Compared to, there is no difference in the discoloration of the tablets, and it retains the same storage stability.
In addition to these, the paroxetine tablet of the present invention is a preparation with good uniformity of paroxetine content in the preparation, has little variation in paroxetine hydrochloride content, exhibits dissolution properties equivalent to conventional tablets, and forms tablets There is no problem in the properties and tablet hardness. For example, the hardness of the obtained tablet is 3.0 to 6.0 kgf, preferably 4.0 to 5.0 kgf, and the hardness of the coated tablet is 5.0 to 11.0 kgf, preferably It is the range of 7.0-10.0 kgf. Both uncoated tablets and coated tablets have favorable hardness. Further, the tableting property of the tablet is good, there is little variation in weight, and the quality is excellent.

  Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto.

Examples 1 and 2
Paroxetine-containing tablets were obtained by the following formulation and production method.
8.75 parts of paroxetine hydrochloride hemihydrate and 88.75 parts of calcium hydrogenphosphate hydrate (trade name FF-100) were uniformly mixed, and then kneaded with water as appropriate. It granulated with the granulator (the product made from Paulek, VG-01). After granulation, drying was performed at 60 ° C. for 4 hours in a shelf dryer, and then sieved with a 30-mesh sieve for sizing. By adding 1.5 parts of sodium carboxymethyl starch (manufactured by ROQUETTE) and 1.0 part of magnesium stearate (manufactured by Ohira Chemical Industry Co., Ltd.) to 97.5 parts of the resulting granulated product, and mixing, Got.
Using a rotary tableting machine (manufactured by RIVA SA), the tableting powder was tableted with 10 mg of paroxetine, with a tablet diameter of 6.5 mm and a tablet hardness of 4.0 to 4.5 kgf, 20 mg. Tablets with tablet hardness of 4.5 to 5.0 kgf were formed in a shape with a heel diameter of 7.5 mm and 8.0 mm, and uncoated tablets of each tablet were produced. The obtained round tablet has a tablet diameter of 6.5 mm and a tablet thickness of 2.7 mm for a 10 mg tablet, and the composition in one tablet is as shown in Table 2. For a 20 mg tablet, the tablet diameter is 7 mm. 0.5 mm and the tablet thickness were 3.8 mm, or the tablet diameter was 8.0 mm and the tablet thickness was 3.5 mm.

Examples 3 and 4
Manufacture of coated tablets 13.75 parts of polyethylene glycol 6000 (trade name: Macrogol RTM6000, manufactured by NOF Corporation) and 72.49 parts of hypromellose (manufactured by Shin-Etsu Chemical Co., Ltd.) were added to heated purified water, and dissolved with stirring. Purified water in which 13.75 parts of titanium oxide and 0.017 parts of iron sesquioxide were dispersed was added and mixed uniformly to prepare a film coating solution.
The uncoated tablets obtained in Examples 1 and 2 were put into a film coating apparatus (manufactured by Freund Sangyo) and coated with the above film coating solution. An appropriate amount of carnauba wax is added to the obtained film-coated tablet for polishing, and a film-coated tablet containing 10 mg of circular paroxetine having a tablet diameter of 6.6 mm, a tablet thickness of 2.8 mm, and a mass of 135 mg, or a tablet diameter of Circular paroxetine 20 mg-containing film-coated tablets each having a thickness of 7.6 mm, a tablet thickness of 3.9 mm, or a tablet diameter of 8.1 mm, a tablet thickness of 3.6 mm, and a mass of 268 mg were obtained.
The coating composition per tablet was as shown in Table 4 [10 mg tablet] and Table 5 [20 mg tablet].

The uncoated tablet containing 10 mg of paroxetine according to the present invention was used in Example 1, the 20 mg uncoated tablet was used in Example 2, the film-coated tablet containing 10 mg of paroxetine was used as Example 3, and the 20 mg tablet was used as Example 4. In addition, as commercial paroxetine preparations, trade name Paxil ^RTM tablets 10 mg and 20 mg, Comparative Example 3 and Comparative Example 4, respectively, and tablets with these film coatings peeled off as Comparative Example 1 and Comparative Example 2, respectively, The test was conducted.

Test example 1
Comparison of size and total amount Using the paroxetine-containing film-coated tablets obtained in Examples 3 and 4, the size and total amount were compared with those of Comparative Examples 3 and 4. The results are shown in Table 6.

Test example 2
Measurement of color difference The uncoated tablets and film-coated tablets of Examples 1 and 3 and Comparative Examples 1 and 3 were exposed to light with an optical tester in an unwrapped state, and the color tone of the tablet surface at a cumulative illuminance of 1,200,000 Lux · hr. The change was measured with a color difference meter (model name CR-300: manufactured by Minolta). In addition, the film-coated tablets of Example 1 and Comparative Example 1 were stored in an incubator at 40 ° C. and 75% relative humidity for 1 month without packaging, and the color tone change on the tablet surface was measured in the same manner. The results are shown in Table 7.
The ΔE value of Example 3 was the same as or smaller than that of Comparative Example 3, and the discoloration was small.
From this, tablets granulated using only water have the same tablet discoloration prevention effect as the conventional tablets considered to have been produced by the dry direct compression method, which is the conventional technique shown in Comparative Example 3. It was confirmed that

Test example 3
Content uniformity test One tablet was sampled, 10 mL or 20 mL of diluted hydrochloric acid was added and disrupted by ultrasonic treatment, 2 mL or 4 mL of the internal standard solution was accurately added, and methanol was added to 50 mL or 100 mL. This solution was centrifuged, 5 mL of the supernatant was taken, and methanol was added to make 10 mL, which was used as a sample solution. Separately, about 57 mg of paroxetine hydrochloride hydrate for quantification was accurately weighed and dissolved in methanol, 10 mL of the internal standard solution was accurately added, and methanol was added to make 100 mL. 2 mL of this solution was taken, 1 mL of diluted hydrochloric acid was added, and methanol was added to 10 mL to obtain a standard solution. A mobile phase was prepared by adding acetic acid (100) to a 0.05 mol / L ammonium acetate buffer / methanol / triethylamine mixed solution (60: 40: 1) adjusted to pH 5.5, and the internal standard solution was paraoxygen. A mobile phase solution of methyl benzoate was obtained. Tests were performed using the internal standard method of liquid chromatography, and the ratio of the peak area of paroxetine to the peak area of the internal standard was determined. The results are shown in Table 8.
The tablets of Examples 3 and 4 (each n = 5) had better or equal content uniformity compared to the tablets of Comparative Examples 3 and 4 (each n = 3). In Example 4, a tablet having a diameter of 8.1 mm was used.

Test example 4
Dissolution test One tablet was taken, and 900 mL of 0.1 mL / L hydrochloric acid test solution was used, and the dissolution test was performed at 50 rotations per minute by the paddle method.
Sampling at each time, filtering with a membrane filter, adding 1 mL of internal standard solution to 1 mL of this filtrate, adding 1 mL of mobile phase to make a sample solution, and testing by the internal standard method of liquid chromatography It was. A mobile phase was prepared by adding acetic acid (100) to a 0.05 mol / L ammonium acetate buffer / methanol / triethylamine mixed solution (60: 40: 1) adjusted to pH 5.5, and the internal standard solution was paraoxygen. The peak area ratio of paroxetine with respect to the peak area of the internal standard was determined using a mobile phase solution of methyl benzoate. The results are shown in Table 9.
The tablet of Example 4 showed almost the same dissolution behavior as Comparative Example 4. In Example 4, a tablet having a diameter of 7.6 mm was used. Thereby, even when the mass of the tablet per tablet was reduced, it was confirmed that it has the same dissolution property as that of the conventional tablet.

Test Example 5
Stability / Purity Test The film-coated tablets of Example 4 and Comparative Example 4 were unwrapped in a 40 ° C. and 75% relative humidity incubator for 1 month, in a 60 ° C. incubator for 4 weeks, 60 ° C. and 75% relative humidity. Was stored in an incubator for 4 weeks, and a purity test was performed on tablets under various conditions.
The tablet was powdered, and the amount corresponding to 10 mg of paroxetine hydrochloride hydrate was taken according to the indicated amount, and 10 mL of a water / tetrahydrofuran mixture (9: 1) was added and shaken. This solution was centrifuged, and the supernatant was used as a sample solution. 1 mL of this solution was accurately weighed, and a water / tetrahydrofuran mixture (9: 1) was added to make exactly 100 mL to obtain a standard solution. Water / tetrahydrofuran / trifluoroacetic acid mixture (180: 20: 1) as mobile phase A, acetonitrile / tetrahydrofuran / trifluoroacetic acid mixture (180: 20: 1) as mobile phase B, mobile phase A and mobile phase B A mobile phase with a concentration gradient controlled by changing the mixing ratio was fed and tested by liquid chromatography. The peak areas of each of the sample solution and the standard solution were measured by an automatic integration method. The results are shown in Table 10.
The purity of Example 4 was superior to that of Comparative Example 4 in any stability test under each condition. In Example 4, a tablet having a diameter of 8.1 mm was used. From this, the film-coated tablet of Example 4 granulated using only water is almost the same as the conventional tablet considered to be produced by the dry direct tableting method which is the conventional technique shown in Comparative Example 4. It was confirmed to have the stability of

  According to the present invention, while containing paroxetine in the same amount as the conventional preparation, it is miniaturized, has sufficient hardness as a practical tablet, has excellent dissolution properties, and is administered in comparison with conventional paroxetine tablets. It is possible to provide a tablet having the feature of being easily processed. Furthermore, since the oral tablet containing paroxetine hydrochloride of the present invention does not use an organic solvent in the production process, it also has the characteristics that it does not cause problems such as adverse health effects on workers, environmental pollution, and residue in the preparation. .

Claims (5)

  A paroxetine hydrochloride-containing oral tablet characterized by being produced by a wet granulation method using only water as a solvent.   The oral tablet containing paroxetine hydrochloride according to claim 1, wherein the wet granulation method is a stirring granulation method.   The paroxetine hydrochloride-containing oral tablet according to claim 1 or 2, wherein the mass per uncoated tablet is 16 parts by mass or less with respect to 1 part by mass of paroxetine.   The paroxetine hydrochloride-containing oral use according to claim 1, wherein the mass per uncoated tablet is 100 to 160 mg for a 10 mg tablet and 200 to 320 mg for a 20 mg tablet. tablet.   The paroxetine hydrochloride-containing oral tablet according to claim 1, wherein the mass per uncoated tablet is 130 mg for a 10 mg tablet and 260 mg for a 20 mg tablet.

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