KR20070009934A - Sustained-release tablet containing paroxetine hydrochloride and manufacturing method thereof - Google Patents

Abstract

A sustained-release tablet comprising paroxetine hydrochloride is provided to show low initial discharge rate of the paroxetine hydrochloride and be able to discharge the paroxetine hydrochloride at almost zero-order speed for about 12 hours. The sustained-release tablet comprises paroxetine hydrochloride, a high viscous polymer such as a high viscous hydroxypropylmethylcellulose, a mixture polymer consisting of polyvinyl acetate and povidone in a weight ratio of 8:2 and ethyl cellulose, a low viscous hydroxypropylmethylcellulose, and a pharmaceutically acceptable excipient such as a mixture of mannitol and lactose.

Description

Sustained-release tablet of paroxetine hydrochloride and its preparation method {sustained-release tablet containing paroxetine hydrochloride and manufacturing method}

1 is a graph showing the dissolution rate (%) of paroxetine hydrochloride sustained-release tablet over time.

The present invention relates to a sustained release tablet of paroxetine hydrochloride and a preparation method thereof.

Paroxetine hydrochloride is a selective serotonin reuptake inhibitor (SSRI) that is used to treat depression and / or anxiety disorders.

SSRI-based depression and / or anxiety disorders, such as paroxetine hydrochloride, are often discontinued due to adverse reactions in the early stages of treatment, such as nausea, drowsiness, and fatigue. Considering how to treat depression is very undesirable. As with psychiatric drugs, sudden discontinuation of medication may cause side effects such as dizziness, sensory disturbances, sleep disorders, anxiety, nausea, and sweating, so it is advisable to stop the medication slowly rather than temporarily discontinue the medication. Do.

Because of these problems, sustained-release formulations that release the drug in a consistent pattern after dosing and have a relatively long duration of action are preferred for the treatment of depression and / or anxiety disorders. Smithkline's Paroxetine controlled-release tablet.

However, Pacyl CR Tablet ™ is a sustained release bilayer tablet consisting of an active layer and a support-platform containing paroxetine hydrochloride, and its manufacturing method is complicated and requires a special machine (a tableting machine capable of producing a double layer) for mass production. have.

Therefore, the technical problem to be achieved by the present invention is to provide a slow release tablet of paroxetine hydrochloride that can be released close to the zero order rate for about 12 hours low initial release rate of paroxetine hydrochloride.

Another technical problem to be achieved by the present invention is to provide a method for preparing paroxetine sustained-release tablet hydrochloride that is simple, economical and does not require a special machine for mass production.

In order to achieve the above technical problem, the present invention provides a paroxetine sustained-release tablet characterized in that it comprises a paroxetine hydrochloride, a high viscosity polymer, a low viscosity hydroxypropylmethylcellulose and a pharmaceutically acceptable excipient.

More preferably, the present invention is hydrochloric acid, characterized in that the high viscosity polymer is any one or more selected from the group consisting of high viscosity hydroxypropylmethyl cellulose, polyvinylacetate and povidone 8: 2 (w / w) mixed polymer and ethyl cellulose Provides slow release of paroxetine.

More preferably, the present invention provides a sustained-release paroxetine hydrochloride, characterized in that the viscosity of the high viscosity hydroxypropylmethyl cellulose is 3,000 to 5,600 cP (2wt% aqueous solution, 20 ℃).

More preferably, the present invention provides a sustained-release tablet of paroxetine hydrochloride, characterized in that the high viscosity polymer is a mixture of high viscosity hydroxypropylmethylcellulose and polyvinylacetate and a mixture of 8: 2 (w / w) of povidone.

More preferably, the present invention provides a slow release tablet of paroxetine hydrochloride, wherein the low viscosity hydroxypropylmethylcellulose has a viscosity of 80 to 120 cP (2 wt% aqueous solution, 20 ° C.).

More preferably, the present invention provides sustained-release paroxetine hydrochloride, characterized in that the pharmaceutically acceptable excipient comprises a mixture of mannitol and lactose.

The present invention also provides 6 to 14% by weight of paroxetine hydrochloride relative to the total weight of the sustained-release tablet; 6 to 20 wt% high viscosity polymer; 20 to 40% by weight of low viscosity hydroxypropylmethylcellulose; And 30 to 60% by weight of a pharmaceutically acceptable excipient.

More preferably, the present invention is hydrochloric acid, characterized in that the high viscosity polymer is any one or more selected from the group consisting of high viscosity hydroxypropylmethyl cellulose, polyvinylacetate and povidone 8: 2 (w / w) mixed polymer and ethyl cellulose Provides slow release of paroxetine.

More preferably, the present invention is that the high-viscosity polymer is composed of 4 to 10% by weight of a mixed polymer of polyvinylacetate and povidone of 8-2 (w / w) and 2 to 10% by weight of high-viscosity hydroxypropylmethylcellulose Provided is a sustained release tablet of paroxetine hydrochloride.

More preferably, the present invention provides sustained-release paroxetine hydrochloride, characterized in that the pharmaceutically acceptable excipient is a mixture of mannitol and lactose.

The invention also comprises the steps of mixing (S1) paroxetine hydrochloride and mannitol; (S2) dissolving 8: 2 (w / w) mixed polymer or ethyl cellulose of polyvinylacetate and povidone in a lower alcohol to prepare a binder solution; (S3) preparing granules using the mixture of (S2) and the mixture of (S1); (S4) mixing and tableting the granules of step (S3), high viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl cellulose, and a pharmaceutically acceptable excipient; And (S5) enteric-coating the tablet prepared in step (S4). Provides a method for producing paroxetine hydrochloride sustained-release tablet comprising a.

More preferably, the present invention further comprises at least one selected from the group consisting of pharmaceutically acceptable excipients, 8: 2 (w / w) mixed polymer of polyvinylacetate and povidone and ethylcellulose in the step (S1). Provided is a method for preparing paroxetine hydrochloride sustained-release tablet, characterized in that the mixing.

Hereinafter, paroxetine hydrochloride sustained-release tablet of the present invention and a preparation method thereof will be described in more detail.

The present invention provides a paroxetine hydrochloride sustained-release tablet comprising a paroxetine hydrochloride, a high viscosity polymer, a low viscosity hydroxypropyl methyl cellulose and a pharmaceutically acceptable excipient, more preferably the high viscosity polymer is a high viscosity hydroxy Provided is a slow release tablet of paroxetine hydrochloride, characterized in that any one or more selected from the group consisting of 8: 2 (w / w) mixed polymer of propylmethylcellulose, polyvinylacetate and povidone, and ethylcellulose.

In the present invention, the viscosity of a polymer having a viscosity indicates a viscosity (cP) measured at 20 ° C. by preparing a 2% by weight aqueous solution with the polymer and refers to an average value measured and averaged three or more times in view of the characteristics of the polymer. The high viscosity hydroxypropyl methyl cellulose in the present invention preferably has a viscosity of 3,000 to 5,600 cP, and the low viscosity hydroxypropyl methyl cellulose in the present invention preferably has a viscosity of 80 to 120 cP.

In general, the release of the drug is controlled by adding a release-controlling polymer, and it is common to control the amount of the release-controlling polymer used to meet the desired release rate. However, the same formulation does not apply to all drugs, and different release patterns depend on the properties of the drug (eg solubility), excipients added with the drug (binders, fillers, lubricants, etc.), manufacturing methods, etc. It is well known to those skilled in the art to which the present invention pertains.

The present invention is based on the following surprising findings that occur when the drug is paroxetine hydrochloride.

First, in the case of sustained-release tablets of paroxetine hydrochloride prepared using only high-viscosity polymers (eg, high viscosity hydroxypropylmethylcellulose) or poorly soluble polymers (eg, ethyl cellulose), the drug release pattern has a parabolic shape, As the time progresses, the release pattern is gradually slowed down. Therefore, in order to control the release of paroxetine hydrochloride, only a high viscosity polymer or a poorly soluble polymer is used to prepare a sustained-release tablet which releases the drug at near zero order rate for about 12 hours. It is impossible. This is very undesirable considering the treatment of depression, which is desirable to lower the initial drug release rate in order to reduce initial adverse reactions such as nausea, drowsiness and fatigue.

Second, paroxetine hydrochloride sustained-release tablet prepared using only low viscosity polymer is difficult to control the release rate, so the release of paroxetine hydrochloride is too fast, the dissolution deviation is relatively very large. In addition, when the initial dissolution rate of paroxetine hydrochloride sustained-release tablet is preferably controlled using only low viscosity polymer, the latter dissolution rate may be lowered and the final dissolution rate may be decreased. In addition, when controlling the release of paroxetine hydrochloride using only low-viscosity polymers, the amount of low-viscosity polymers required is too large to increase the weight of one tablet and, as a result, the handleability and marketability of the formulation are poor.

Third, when a suitable mixture of high viscosity polymer and low viscosity hydroxypropyl methyl cellulose is used, it is easy to prepare a sustained-release tablet which releases paroxetine hydrochloride at a constant rate for about 12 hours.

The present invention also relates to the group of high viscosity hydroxypropylmethylcellulose, 8: 2 (w / w) mixed polymer of polyvinylacetate and povidone (eg Kollidon SR ™, BASF, Germany) and ethyl cellulose. It provides a sustained-release tablet of paroxetine hydrochloride characterized in that at least one selected from, more preferably, the present invention is a high viscosity polymer of high viscosity hydroxypropyl methyl cellulose and polyvinylacetate and povidone 8: 2 (w / w) mixed polymer It provides a sustained release tablet of paroxetine hydrochloride characterized in that the mixture. It was much easier to control the dissolution rate when mixed with high viscosity hydroxypropylmethylcellulose or polyvinylacetate and 8: 2 (w / w) mixed polymer of povidone alone. It was.

More preferably, the present invention also provides sustained release paroxetine hydrochloride, characterized in that the pharmaceutically acceptable excipient is a mixture of mannitol and lactose. Since paroxetine hydrochloride is unstable in water, the stability of the paroxetine sustained-release tablet can be ensured by using mannitol having little moisture resistance and a low moisture content as a filler. However, when only mannitol was used as a filler, sticking occurred frequently during tableting, and this problem could be overcome by using a mixture of mannitol and lactose as a filler. In addition, anhydrous lactose is more preferable than hydrous lactose in consideration of water instability of paroxetine hydrochloride, and lactose as used herein refers to hydrous lactose, anhydrous lactose, or a mixture thereof.

The present invention also provides 6 to 14% by weight of paroxetine hydrochloride relative to the total weight of the sustained-release tablet; 6 to 20 wt% high viscosity polymer; 20 to 40% by weight of low viscosity hydroxypropylmethylcellulose; And 30 to 60% by weight of a pharmaceutically acceptable excipient.

More preferably, the high viscosity polymer is hydrochloric acid, characterized in that any one or more selected from the group consisting of 8: 2 (w / w) mixed polymer of polyvinylacetate and povidone, high viscosity hydroxypropylmethyl cellulose and ethyl cellulose. To provide a sustained-release paroxetine tablet, more preferably, the present invention is a high viscosity polymer of 8 to 2 (w / w) mixed polymer of polyvinylacetate and povidone with respect to the total weight of the sustained-release tablet 4 to 10% by weight and high viscosity hydroxypropylmethylcellulose 2 to It provides a sustained-release tablet of paroxetine hydrochloride, characterized in that consisting of 10% by weight.

More preferably, the present invention provides sustained-release paroxetine hydrochloride, characterized in that the pharmaceutically acceptable excipient is a mixture of mannitol and lactose.

Even in tablets with the same components, the release rate varies depending on the content of the drug. In the case of slow-release tablets, the content of one component is different because the content of one component changes as a result. Has a great effect on the release rate of the drug.

Preferred drug release patterns depend on the treatment of depression and / or anxiety disorders, although the content ratios do not limit the basic idea of the present invention, when the components and content (ratios) of the present invention, paroxetine hydrochloride sustained-release tablets are initially treated with paroxetine hydrochloride. Low release rate and drug release pattern close to zero order rate for about 12 hours, suggesting the most desirable release pattern according to current therapy.

The invention also comprises the steps of mixing (S1) paroxetine hydrochloride and mannitol; (S2) dissolving 8: 2 (w / w) mixed polymer or ethyl cellulose of polyvinylacetate and povidone in a lower alcohol to prepare a binder solution; (S3) preparing granules using the mixture of (S2) and the mixture of (S1); (S4) mixing and tableting the granules of step (S3), high viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl cellulose, and a pharmaceutically acceptable excipient; And (S5) enteric-coating the tablet prepared in step (S4). Provides a method for producing paroxetine hydrochloride sustained-release tablet comprising a.

More preferably, the present invention further comprises any one or more selected from the group consisting of 8: 2 (w / w) mixed polymer of pharmaceutically acceptable excipient, polyvinylacetate and povidone, and ethylcellulose in the step (S1). Provided are a method for producing paroxetine hydrochloride sustained-release tablet, characterized in that mixing.

Since paroxetine hydrochloride is slightly acidic and contains a very small amount in one tablet, there is a high possibility of content deviation during the manufacturing process of tableting. This content deviation was largely solved by preparing paroxetine hydrochloride and mannitol in granules together. In addition to the paroxetine and mannitol hydrochloride, for the ease of granulation, pharmaceutically acceptable fillers such as lactose and / or some of the release controlling polymers which are postmixed after granulation may be included in the granules. The release control polymer acts as a binder during granulation production and increases the binding force of the granules to facilitate subsequent processes such as transporting and tableting, as well as maintaining uniform binding of paroxetine hydrochloride with other components. It is thought to play a role in controlling the dissolution rate and dissolution deviation.

In addition, since paroxetine hydrochloride is unstable in water, it is preferable to use a lower alcohol as a solvent for producing granules, more preferably ethanol, isopropyl alcohol or a mixture thereof.

Sustained release tablets of the present invention may be enteric coated to be released in the small intestine rather than being released in the stomach. In this case, the release of paroxetine hydrochloride is delayed by the time when the enteric coating membrane is dissolved or destroyed.

Hereinafter, the present invention will be described in more detail with reference to Examples. The following examples are presented to illustrate the invention by way of example and should not be construed as limiting the scope of the invention.

<Manufacture of Examples 1-3 and Comparative Examples 1-7>

Sustained-release tablets containing paroxetine hydrochloride were prepared with the ingredients and contents shown in Table 1 below.

Example 1, Example 2, and Comparative Example 1 were prepared as follows. All of components 1, 6 and 7 and about 2.2 g of component 2 were mixed. Then, after preparing the granules using the binder solution and the mixture prepared by dissolving the remaining two components in 7.5 ml of ethanol, and dried at 40 ℃ until the loss on drying (about 2.5%), 30 mesh sieve It was established as (sieve). Thereafter, the mixture was mixed well with the remaining ingredients and tableted with a tableting machine (KI-1300, Kisan Machinery, Korea) so that the weight of one tablet was about 150 mg.

Example 3 was prepared as follows. Ingredients 1, 6 and 7 were mixed. Then, granules were prepared using the binder solution prepared by dissolving the second component in 13 ml of ethanol and the mixture, and dried at 40 ° C. until the loss on drying was about 2.5%. sieve). Thereafter, the mixture was mixed well with the remaining ingredients and tableted with a tableting machine (KI-1300, Kisan Machinery, Korea) so that the weight of one tablet was about 150 mg.

Comparative Example 2 was prepared as follows. Ingredients 1, 6 and 7 were mixed. Then, granules were prepared using the binder solution prepared by dissolving the second component in 7.5 ml of ethanol and the mixture, and dried at 40 ° C. until the loss on drying was about 2.5%. sieve). Thereafter, the mixture was mixed well with the remaining ingredients and tableted with a tableting machine (KI-1300, Kisan Machinery, Korea) so that the weight of one tablet was about 150 mg.

Comparative Example 3 and Comparative Example 5 were prepared as follows. After mixing No. 1, No. 6 and No. 7, the granules were prepared using the above mixture and 0.9 g of No. 3 in 8 ml of ethanol, and the loss on drying was about 2.5. It was dried at 40 ° C. until it became% and was established in a 30 mesh sieve. Thereafter, the mixture was mixed well with the remaining ingredients and tableted with a tableting machine (KI-1300, Kisan Machinery, Korea) so that the weight of one tablet was about 150 mg.

Comparative Example 4, Comparative Example 6 and Comparative Example 7 were prepared as follows. After mixing Nos. 1, 6 and 7, 0.7 g of No. 2 was dissolved in 7.5 ml of ethanol and granules were prepared using the above mixture, and the loss on drying was about 2.5%. It dried at 40 degreeC until it became, and it settled into 30 mesh sieves. Thereafter, the mixture was mixed well with the remaining ingredients and tableted with a tableting machine (KI-1300, Kisan Machinery, Korea) so that the weight of one tablet was about 150 mg.

number Ingredient (unit: g) Example Comparative example One 2 3 One 2 3 4 5 6 7 One Paroxetine hydrochloride 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4.3 2 Kollidon SR ™ 3.2 3.5 - 3.2 0.9 - 6.0 - 7.5 10.5 2 Ethyl cellulose - - 1.8 - - - - - - - 2 TEC - - 0.2 - - - - - - - 3 HPMC 100 13.5 13.5 18.0 15.0 15.0 18.0 - 15.0 - - 4 HPMC 4,000 2.7 3.0 - - - - - - - - 5 Kollidon K-90F ™ - - - - - - 4.5 - 3.0 - 6 Mannitol 9.0 9.0 9 9.0 9.0 9.0 9.0 9.0 9.0 9.0 7 Lactose 11.7 11.1 11.3 12.9 15.4 12.4 18.3 13.3 18.2 18.2 8 Mg-stearate 0.7 0.7 0.5 0.7 0.5 0.5 3.0 0.5 3.0 3.0 9 Stearic acid - - - - - - 3.0 - - Kollidon SR ™: 8: 2 (w / w) mixed polymer of polyvinylacetate and povidone TEC: triethyl citrate (plasticizer) HPMC 100: hydroxypropylmethylcellulose 100 cP HPMC 4,000: hydroxypropylmethylcellulose 4,000 cP Kollidon K-90F ™: povidone (polyvinylpyrrolidone), BASF, Germany Mg-stearate: magnesium stearate (lubricant)

<Elution evaluation of Examples 1-3 and Comparative Examples 1-7>

The samples prepared in Examples 1 to 3 and Comparative Examples 1 to 7 were subjected to the dissolution test according to the paddle method (100 rpm, 900 ml) of the Korean Pharmacopoeia dissolution test. As the eluting medium, the second pharmacopeia dissolution test solution (pH 6.8 buffer) was used, and Pacsil CR tablet ™ (Glaxo Smith Clime, Korea) was used as a control. All six samples were tested and their average values are shown in Table 2 and FIG. 1, and the amount of paroxetine hydrochloride eluted with the elution medium relative to the initial content contained in one tablet was expressed as a percentage (%).

Hour (hr) Dissolution rate (%) Control Example Comparative example One 2 3 One 2 3 4 5 6 7 0.5 0.5 4.8 3.5 4.8 5.7 9.7 10.1 11.3 5.1 6.2 17.9 One 3.2 12.3 8.1 9.6 13.9 18.3 19.2 18.3 7.0 11.6 25.9 1.5 8.5 18.8 15.1 16.2 22.9 27.3 28.8 26.9 11.8 19.1 31.1 2 14.0 25.7 20.8 21.8 32.6 34.6 37.2 37.8 16.7 25.4 37.3 3 27.5 37.2 31.6 33.2 52.1 51.0 53.1 52.2 27.0 36.3 45.0 4 41.3 48.8 44.0 44.2 70.8 68.5 67.1 57.7 38.2 44.1 48.8 5 53.3 58.4 54.9 51.0 86.7 81.9 79.5 59.9 45.4 48.6 53.1 6 62.7 67.7 62.3 59.4 97.2 88.6 87.8 61.3 52.3 50.4 56.6 8 76.1 81.2 75.2 72.8 99.2 94.4 94.0 61.9 56.2 53.5 59.4 10 84.5 88.9 85.0 85.8 98.8 100.3 101.0 62.5 58.6 53.8 62.7

As shown in Table 2, it can be seen that the slow release tablet of paroxetine hydrochloride of the present invention similarly to the control releases the drug in a pattern similar to the zero order rate over about 12 hours. As can be seen from the elution results of Comparative Examples 4, 6, and 7, when only the high viscosity polymer is used, the elution rate decreases rapidly with time, and the elution rate at 10 hours is very low. In particular, as can be seen in Comparative Example 7, in the case of using only a high viscosity polymer in the sustained-release tablet containing paroxetine hydrochloride, although the initial dissolution rate is fast, the latter dissolution rate is very low. As can be seen from the results of Comparative Examples 1, 2 and 3, when only the low viscosity hydroxypropyl methyl cellulose, which is a low viscosity release controlling polymer, was used, drug release could not be controlled to a desired degree. Although a significant increase in the content of low-viscosity hydroxypropylmethylcellulose was able to control the release to some extent, the size of one tablet was so large that the handleability and marketability of the formulation were very poor. Comparative Example 5 is a result showing that the drug release pattern is not preferable even when the paroxetine sustained-release tablet is prepared using low viscosity hydroxypropylmethylcellulose and poorly soluble materials (eg, stearic acid) which are often used as components for controlling release. Indirectly indicates that the preparation of paroxetine hydrochloride sustained-release tablet is not easy.

Considering these results and the slow release tablet of paroxetine hydrochloride of the present invention, the preparation of the slow release tablet of paroxetine hydrochloride and the preparation method thereof according to the present invention are very useful.

The present invention provides a sustained release tablet of paroxetine hydrochloride which has a low initial release rate of paroxetine hydrochloride and is capable of releasing near zero order rate for about 12 hours, and the present invention also provides a method for preparing a slow release tablet of paroxetine hydrochloride with low content deviation. do.

Claims (12)

A paroxetine sustained-release tablet comprising hydrochloric acid paroxetine, a high viscosity polymer, a low viscosity hydroxypropylmethylcellulose, and a pharmaceutically acceptable excipient. According to claim 1, wherein the high viscosity polymer is paroxetine hydrochloride, characterized in that any one or more selected from the group consisting of high viscosity hydroxypropyl methyl cellulose, polyvinylacetate and povidone 8: 2 (w / w) mixed polymer and ethyl cellulose Sustained release. The sustained-release tablet of paroxetine hydrochloride according to claim 2, wherein the high viscosity hydroxypropylmethylcellulose has a viscosity of 3,000 to 5,600 cP. 3. The sustained-release tablet of paroxetine hydrochloride according to claim 2, wherein the high viscosity polymer is a mixture of high viscosity hydroxypropylmethylcellulose and 8: 2 (w / w) mixed polymer of polyvinylacetate and povidone. According to claim 1, wherein the low viscosity hydroxypropyl methyl cellulose paroxetine hydrochloride sustained-release tablet, characterized in that the viscosity of 80 to 120 cP. The sustained-release tablet of paroxetine hydrochloride according to claim 1, wherein the pharmaceutically acceptable excipient contains a mixture of mannitol and lactose. 6-14% by weight of paroxetine hydrochloride relative to the total weight of the sustained-release tablet; 6 to 20 wt% high viscosity polymer; 20 to 40% by weight of low viscosity hydroxypropylmethylcellulose; And 30 to 60% by weight of a pharmaceutically acceptable excipient. 8. The paroxetine hydrochloride according to claim 7, wherein the high viscosity polymer is at least one selected from the group consisting of high viscosity hydroxypropylmethyl cellulose, polyvinylacetate and povidone 8: 2 (w / w) mixed polymer, and ethyl cellulose. Sustained release. According to claim 7, wherein the high viscosity polymer is composed of 4 to 10% by weight of a mixed polymer of polyvinylacetate and povidone of 8 to 2 (w / w) and 2 to 10% by weight of high viscosity hydroxypropylmethylcellulose relative to the total weight of the sustained-release tablet Paroxetine hydrochloride sustained-release tablet using. 8. The sustained release tablet of paroxetine hydrochloride according to claim 7, wherein the pharmaceutically acceptable excipient is a mixture of mannitol and lactose. (S1) mixing paroxetine hydrochloride and mannitol; (S2) dissolving 8: 2 (w / w) mixed polymer or ethyl cellulose of polyvinylacetate and povidone in a lower alcohol to prepare a binder solution; (S3) preparing granules using the mixture of (S2) and the mixture of (S1); (S4) mixing and tableting the granules of step (S3), high viscosity hydroxypropyl cellulose, low viscosity hydroxypropyl cellulose, and a pharmaceutically acceptable excipient; And (S5) enteric coating the tablet prepared in step (S4); A method for producing paroxetine hydrochloride sustained-release tablet comprising a. The method of claim 11, wherein in step (S1) further mixed with any one or more selected from the group consisting of pharmaceutically acceptable excipients, polyvinylacetate and povidone 8: 2 (w / w) mixed polymer and ethyl cellulose A method for producing paroxetine hydrochloride sustained-release tablet, characterized in that.

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