KR101076648B1 - Controlled-release Aceclofenac Containing Oral Drug Preparations and it's Manufacturing Process - Google Patents

Abstract

The present invention relates to a method of preparing double- and single-coated tablets containing aceclofenac and sustained release. Specifically, a granule is prepared by using a polymer compound and a fat-soluble surfactant in a region in which a sustained release is expected. It relates to a method for producing a sustained-release sustained-release tablet obtained by rapid release by containing aceclofenac powder, a disintegrating agent and a pH adjusting agent in the expected part.

An object of the present invention is to improve the release of aceclofenac drug by the controlled release of the ideal near-linear release, and also by adjusting the pH to promote the absorption in the stomach and contains aceclofenac with improved stability and at the same time immediate release and sustained release It is to prepare a double tablet and a single tablet having.

Aceclofenac sustained-release tablet according to the present invention consists of an immediate release layer comprising aceclofenac, a water-soluble additive, a pH adjusting agent, a disintegrant, a filler and a lubricant, and a sustained release layer including aceclofenac, a release controlling polymer, a fat-soluble surfactant, a filler and a lubricant. It is characterized in that the pH adjuster is sodium bicarbonate.

Aceclofenac, sustained-release tablet, dissolution rate, pH adjuster

Description

Controlled-release Aceclofenac Containing Oral Drug Preparations and it's Manufacturing Process

The present invention relates to a method of preparing double- and single-coated tablets containing aceclofenac and sustained release. Specifically, a granule is prepared by using a polymer compound and a fat-soluble surfactant in a region in which a sustained release is expected. It relates to a method for producing a sustained-release sustained-release tablet (속 放 및) and rapid release tablet (얻은 放 얻은) obtained by rapid release by containing aceclofenac powder, a disintegrating agent and a pH adjuster in the expectation. Controlled release of aceclofenac drug to improve the ideal release near the straight line, and also by adjusting the pH to promote absorption in the stomach and to improve the stability of double and single tablets containing aceclofenac and improved immediate release and sustained release To prepare.

Aceclofenac (2-[(2,6-dichlorophenyl) amino] phenylacetoxyacetic acid) is a known compound having the following structural formula, as well as chronic joint diseases of rheumatoid arthritis, osteoarthritis or ankylosing spondylitis, as well as toothache, postoperative Or phenylacetic acid-based anti-inflammatory analgesic showing excellent efficacy for pain after delivery. Compared to anti-inflammatory drugs such as naproxen and diclofenac, the drug is easier to penetrate drugs in inflammatory tissues such as joints and thus has an excellent therapeutic effect due to its excellent blocking effect of prostaglandin. On the other hand, since normal gastrointestinal blockade activity in the stomach mucosa is weak, it is suitable for long-term use due to alleviation of gastrointestinal disorders. In particular, it inhibits the production of interleukin-1, which destroys cartilage in joints, It promotes the production of glycans (Glycosaminoglycan) and has the advantage of preventing the exacerbation of rheumatoid arthritis and osteoarthritis.

Aceclofenac (2-[(2,6-dichlorphenyl) amino] -phenylacetoxyacetic acid) is well soluble in organic solvents and relatively insoluble in water. Aceclofenac is rapidly absorbed from the gastrointestinal tract upon oral administration and is distributed in high concentrations in the kidneys, bladder, liver, thyroid gland, and low concentrations in the eyes, brain, and adipose tissue. Aceclofenac has a time of onset of action within 30 minutes when administered orally, and the time to reach peak blood concentration is about 1.5-2.5 hours, and the duration is about 12 hours. Aceclofenac is the major metabolite of 46-75% of the administered drug as aceclofenac at oral administration at the peak blood concentration (Tmax), with extensive metabolism following T _max . It is also known to be an active drug, and it is known that 4-hydroxydiclofenac and indole derivatives are also observed as other metabolites. Aceclofenac is known to excrete about 66.8% in urine and about 18% in feces during oral administration and the rate of excretion (half life) is about 4 hours.

The clinical features of aceclofenac are 1) suitable for rheumatoid arthritis or osteoarthritis because it blocks the production of interleukin-1, which destroys articular cartilage and promotes the production of glycosaminoglycan, a component of articular cartilage. 2) The gastrointestinal mucosa has minimal effect on the production of normal prostaglandin in gastric mucosa, and 3) the high concentration of drug penetrates into inflammation-prone areas such as joints, which is a strong blocking effect of prostaglandin production.

Various formulation means have been developed to enhance the solubilization or dissolution rate of various poorly soluble drugs in order to improve the dissolution of the soluble drug and to enhance the bioavailability. For example, micronization method, micelle method, solid dispersion method, spray drying method, inclusion complex method, and solubilization method using water-soluble polymers or surfactants are used. However, there are many limitations in commercializing these means in terms of manufacturing method, commerciality and efficiency.

In addition, when a poorly soluble drug is formulated as a tablet, one of the pharmaceutical formulations, disintegration should be preferentially performed during oral administration, and a multi-step process in which a drug mixed with an excipient or the like is dissolved in a digestive or bodily fluid is required for absorption. . Moreover, when tablets are poorly soluble in a substance such as aceclofenac, dissolution rate and dissolution rate are generally not good, so the bioavailability is low and the expression of the drug cannot be properly expressed.

However, when formulated in soft capsules or liquid, the stability of the drug is reduced, but when prepared as a tablet has the advantage of increasing the stability of the drug.

Aceclofenac is currently being developed and marketed in the form of tablets and solubilized soft capsules, but due to the nature of patients with musculoskeletal pain, it has not been developed into a dosage form that can be taken once daily. Inconvenience in medication guidance and compliance with patients taking long-term aceclofenac preparations may result. The present invention improves the problems of aceclofenac twice daily dosage forms in view of the effects of taking and treating musculoskeletal pain patients. There is an advantage.

In addition, as a result of studying various compositions that can increase the dissolution characteristics and stability against pH change for the purification of aceclofenac, the dissolution rate of aceclofenac and the product of the product using the poorly soluble drugs aceclofenac, a fat-soluble surfactant, and a polymer for controlling the release of a surfactant It was found that the stability was excellent, and the present invention was completed.

It is an object of the present invention to formulate controlled release of aceclofenac once daily use. The preparation according to the present invention prepared by the method as described above is effective for 24 hours by releasing the effective concentration for analgesic, and then releasing the drug continuously for a long time in 200 mg once a day for the release of the effective drug. Can be sustained, and the effective drug concentration is kept constant, thereby increasing the therapeutic effect and simplifying pharmaceutical formulation therapy in patients with musculoskeletal pain, thereby improving patient convenience and dose compliance.

The present invention solves the properties of aceclofenac having a low dissolution rate during processing into a tablet, and provides a sustained-release tablet of aceclofenac and a double tablet having both rapid release and sustained release with excellent dissolution rate and stability to pH.

According to a preferred embodiment of the present invention, a rapid release layer comprising aceclofenac, aceclofenac sustained-release water-soluble additives, pH regulators, disintegrants, fillers and lubricants, and a sustained release comprising aceclofenac, a release controlling polymer, a fat-soluble surfactant, a filler and a lubricant Layer, and sodium hydrogen carbonate is used as a pH adjuster.

According to another embodiment of the present invention, the content of the release controlling polymer contained in the aceclofenac sustained-release tablet is 5% to 20% by weight relative to the total weight of the aceclofenac sustained-release tablet.

According to another embodiment of the present invention, the content of the pH adjusting agent contained in the aceclofenac sustained-release tablet is 0.25% to 1% by weight relative to the total weight of the aceclofenac sustained-release tablet.

According to another embodiment of the present invention, the water-soluble additive included in aceclofenac sustained-release tablet is poloxamer.

According to another embodiment of the present invention, the content of the water-soluble additive included in the aceclofenac sustained-release tablet is 0.75% to 3% by weight based on the total weight of the aceclofenac sustained-release tablet.

Aceclofenac sustained-release tablet according to the present invention is a 200mg once daily dose for the release of an effective drug, initially releasing an effective concentration for analgesia, and then continually releasing the drug for a long time, the drug can be sustained and effective Maintaining a constant drug concentration increases the therapeutic effect and has the advantage of simplifying the pharmaceutical formulation therapy of patients with musculoskeletal pain, thereby improving patient convenience and dose compliance.

According to a preferred embodiment of the present invention, the controlled release aceclofenac preparation of the present invention comprises the steps of firstly preparing aceclofenac with a suitable sustained release agent or by providing a controlled release to aceclofenac by mixing a fat-soluble surfactant and Immediate granules include aceclofenac alone or aceclofenac, a pH adjusting agent and a disintegrant, followed by mixing with other excipients to tablet into single or double tablets.

Aceclofenac sustained-release tablet according to the present invention has a dual structure of the immediate release layer and the sustained release layer to have rapid release at the beginning of oral administration, and has a sustained release property after the immediate release step of the active drug.

The immediate release layer of aceclofenac sustained-release tablet according to the present invention includes aceclofenac, a water-soluble additive, a pH adjuster, a disintegrant, a filler and a lubricant.

The immediate release layer of aceclofenac not only increases the initial analgesic effect by increasing the initial dissolution rate, but may also increase the stability of the drug by converting the pH to a weak alkali.

Aceclofenac drug is an acid labile drug with poor absorption from the stomach. In order to overcome this point, the present invention uses sodium carbonate as a pH regulator in the immediate release layer. The weight ratio of sodium carbonate, which is a pH adjusting agent, to the rapid-release portion for preparing aceclofenac sustained-release tablet that can be administered once daily is 0.25% to 1% by weight, preferably 0.5% to 1% by weight, based on the total weight of the aceclofenac sustained-release tablet. If the weight ratio of sodium carbonate is less than 0.25% by weight, the stabilization effect in acidity is lowered, and when 1% by weight is exceeded, the initial release rate is lowered.

Water-soluble additives included in the immediate release layer of aceclofenac sustained-release tablet according to the present invention NaH ₂ PO _4, KH ₂ PO _4, polyvinylpyrrolidone, polyethylene glycol, gelatin (gelatin), At least one mixture selected from the group consisting of gums, hydrocarbons, celluloses and derivatives thereof, polyethylene oxide and derivatives thereof, polyvinyl alcohol, poloxamers and polymethylacrylates and inorganics Can be. Preferably poloxamer may be used, but is not limited thereto.

The water-soluble additive is intended to increase the initial release rate of the drug by additionally improving the water absorption in the manufacture of oral preparations. Increase drug absorption in the stomach

The weight ratio of the water-soluble additive is 0.75% to 3% by weight based on the total weight of the aceclofenac sustained-release tablet, and preferably 1% to 2.5% by weight. If the weight ratio of the water-soluble additive is less than 0.75% by weight, the initial release rate is lowered, and if it exceeds 3% by weight, the release rate is excessively high.

Disintegrants contained in the immediate release layer of aceclofenac sustained-release tablets are used to absorb water to promote initial disintegration of the formulation, and to promote dissolution of aceclofenac, and examples of disintegrants that may be used in the formulation of the present invention are croscarmellose sodium. (Croscamellose Sodium), Sodium Starch Glycolate, Pregelatinized Starch (Starch 1500 or Premojel), microcrystalline cellulose, Crospovidone, cross-linked povidone ) And other commercially available polyvinylpyrrolidone (PVP, Povidone), low substituted hydroxypropylcellulose (Low substituted), alginic acid, Carboxymethylcellulose, calcium salt and sodium salt , Colloidal silica, colloidal silica, guar gum, magnesium alu The titanium silicate comprises a (Magnesium aluminum silicate), methyl cellulose (methylcellulose), powdered cellulose, starch (starch) and at least one mixture selected from the group consisting of sodium alginate (sodium alginate).

Preferably, the disintegrant includes at least one mixture selected from the group consisting of croscarmellose sodium, sodium starch glycolate, pregelatinized starch, microcrystalline cellulose, crospovidone and commercially available polyvinylpyrrolidone. It includes. More preferably, as the disintegrant, crospovidone, sodium starch glycolate, or microcrystalline cellulose may be used, and is most effective when a mixture of two or more disintegrants is used.

The immediate release layer of aceclofenac sustained-release tablet according to the present invention includes a filler. Fillers used include one or more mixtures selected from the group consisting of microcrystalline cellulose, hard silicic anhydride, pregelatinized starch and lactose.

The immediate release layer of the aceclofenac sustained-release tablet according to the present invention includes a lubricant.

Glidants are used to improve the moldability of oral formulations, such as magnesium stearate, silica oxide (SiO ₂ ), and colloidal silicon dioxide (trade name Aerosil as fumed silica). And one or more mixtures selected from the group consisting of talc.

The lubricant may be included 0.25% to 2.5% by weight of the total weight of the aceclofenac sustained-release tablet. When the lubricant is used in less than 0.28% by weight, there may be a problem in fluidity during tableting, and if it exceeds 2.5% by weight, there may be a problem in lowering hardness when tableting. In particular, as the lubricant, magnesium stearate or colloidal silicon dioxide may be preferably used.

The sustained release layer of aceclofenac sustained-release tablet according to the present invention includes aceclofenac, a release controlling polymer, a fat-soluble surfactant, a filler and a lubricant.

The sustained release layer is a controlled release formulation of aceclofenac once daily use. The preparation according to the present invention prepared by the method as described above, the drug can be sustained for 24 hours by continuously releasing the drug for a long time by 200mg once a day for the release of the effective drug, the effective drug concentration is kept constant It has the advantage of increasing the therapeutic effect and simplifying the pharmaceutical formulation therapy of patients with musculoskeletal pain to improve patient convenience and dosage compliance.

Aceclofenac is a poorly soluble drug, so it is difficult to mix with a release controlling polymer without an additive. In order to solve this problem, in the present invention, a fat-soluble surfactant was used in the sustained release layer to facilitate the mixing of the aceclofenac and the release controlling polymer, and the dissolution rate of a certain portion was controlled.

Any pharmaceutically acceptable polymer can be used as a release controlling polymer, and hydropropylmethyl cellulose, methyl cellulose, ethyl cellulose, hydropropyl cellulose, sodium carboxymethyl cellulose Cellulose derivative composed of sodium carboxymethylcellulose, propylene oxide and its derivatives, polyvinylpyrrolidone (molecular weight 90, trade name Povidone K-90), polyethylene glycol, polyvinyl alcohol ( Polyvinyl alcohols, polyvinylacetate, polyvinylacetate phthalate, polymethacrylate, polymethacrylate polymers (commercially Eudragit polyacrylic acid, polymethacrylate) Of It may be one or a mixture of two or more selected from the group consisting of a conductor (typically carbomer), glycerol monostearate and poloxamer, preferably hydroxypropylmethylcellulose, carbomer, hydroxypropylcellulose, methylcellulose One or a mixture of two or more selected from the group consisting of polyvinylpyrrolidone and polyvinyl alcohol can be used.

When a general release controlling polymer is used, not only the dissolution rate is constant but also most of the active ingredient is released at the beginning of the dose, which is not suitable for sustained-release tablets.

In order to solve this problem, in the present invention, hydroxypropyl methylcellulose was used as a release controlling polymer.

In the case of hydroxypropylmethylcellulose, products of various viscosities are known, and the dissolution rate of aceclofenac sustained-release tablets can be controlled by adjusting the viscosity.

In addition, the weight ratio of hydroxypropylmethylcellulose for preparing aceclofenac sustained-release tablet which can be administered once daily is 3% by weight to 30% by weight, preferably 5% by weight to 20% by weight. If the weight ratio of hydroxyphoromethylmethylcellulose is less than 5% by weight, the initial dissolution rate of aceclofenac becomes too high, and if it exceeds 20% by weight, the elution time becomes long.

Fat-soluble surfactants included in the sustained-release layer of aceclofenac sustained-release tablet according to the present invention include sodium lauryl sulfate and its derivatives, poloxamer and its derivatives, intermediate chain triglycerides (MCT), labrasol labrasol, transcutol, labrafil, labrafac, poloxamer, various polysorbates [e.g., polyoxyethylene sorbitan monolau Latex ('Tween 20'), polyoxyethylene sorbitan monopalmitate (hereinafter 'Tween 40'), polyoxyethylene sorbitan monostearate (hereinafter 'Tween 60') and polyoxyethylene sorbitan monooleate ('Tween 80')], Sorbitan Esters [for example, sorbitan monolaurate ('Span 20'), sorbitan monopalmitate ('Span 40'), sorb Non-mastic monostearate ('Span 60'), small Sorbitan trioleate (hereinafter 'Span 85') Sorbitan tristearate (hereafter 'Span 80') and sorbitan trilaurate (hereinafter 'Span 85') 65 ')], cremophor, PEG-60 hydrogenated castor oil, PEG-40 hydrogenated castor oil, sodium lauryl glutamate glutamate), disodium cocoamphodiacetate, colloidal silica, and at least one selected from the group consisting of at least one, and may be a mixture of two or more. Considering colloidal silicon dioxide is preferred, 1% to 3% by weight of the total weight of aceclofenac sustained-release tablet is included.

If the fat-soluble surfactant is out of the range of 1% by weight to 3% by weight, sticking and laminating may occur during tableting, which may cause problems in tablet molding.

The sustained-release layer of aceclofenac sustained-release tablet according to the present invention includes a filler and a lubricant, and is the same as the filler and the lubricant contained in the immediate release layer.

Controlled release oral formulations according to the invention may be formulated in the form of tablets, compressed masses, granules or capsules containing said granules. Formulation of the oral preparations into tablets may be formulated using a tableting machine commercially available to the extent that it is commonly available for purchase and use. Compression ingots may also be formulated by conventional press equipment, and granules may also be formulated. It may be formulated by a conventional granulator, and capsules containing such granules may also be formulated to be filled therein using commercially available blank capsules and the like, and all of these formulations may be easily performed by those skilled in the art. It is obvious that what can be understood to be known.

In the preparation of the controlled release oral preparation according to the present invention, in the preparation of the oral preparation, (1) a mixing step of mixing aceclofenac, which expects sustained release as an effective pharmacological ingredient, with a polymer base as a binder; (2) a granulation step of preparing wet sustained-release granules by adding a liquid solvent to the mixture obtained in the mixing step; (3) milling the ground granules; (4) It consists of a mixing step of mixing a water-soluble additive and a disintegrating agent of aceclofenac, which is expected to release quickly as an effective pharmacological ingredient.

The granules of (3) and (4) above may be molded into tablets, compressed ingots, or the like, or granulated, and filled into ordinary empty capsules to form a capsule or the like. As the liquid solvent in the granulation step (2), preferably, a liquid solvent selected from the group consisting of water, ethanol, isopropyl alcohol, glycerin, propylene glycol, polyethylene glycol or a mixture of two or more thereof may be used. The present invention is not limited to these. The use of the liquid solvent can facilitate molding into granules. In this case, when the solvent is water alone or a mixed solvent of water and ethanol, 5 to 40% is used based on the total weight of the mixture obtained in the mixing step of (1), more preferably 10 to 20% Can be used. When the amount of the liquid solvent is less than 5%, the binder solution may not be sufficiently distributed in the granules, there may be a tablet tablet hardness problem, on the contrary, when the amount exceeds 40%, the binder solution is excessively used to dry the granules. This may take a long time and may have the problem of delaying the dissolution of aceclofenac.

In addition, the molding step of the granules (3), (4) can be molded into tablets by tableting directly using a general tablet machine. In particular, according to the present invention, one single mixture can be molded into tablets or the like by simple tableting, and can also be formulated simply and easily using equipment such as a conventional mixer, grinder, and tableting machine using a double tableting machine. There is no need for additional equipment cost, and has the advantage of being easily formulated into a formulation with high productivity.

With the above granules, using the double tableting tablet machine to separate and release the immediate release layer and the sustained release layer may bring about more certain effects of the invention, but the invention is not limited thereto.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, these examples do not limit the scope of the present invention.

<Examples 1 to 4>

A rapid release granules were prepared by mixing aceclofenac, lactose, microcrystalline cellulose, sodium bicarbonate, poloxamer, crospovidone, and magnesium stearate as shown in Table 1 in the immediate release layer.

In the western layer, aceclofenac, lactose and microcrystalline cellulose were mixed evenly to increase the fluidity of the drug. As the polymer base, hydroxypropylmethylcellulose (hydroxypropylmethylcellulose, HPMC 100,000 cps) and povidone were put into a powder mixer, mixed uniformly, and then sprayed with ethanol to prepare wet granules. The component amounts of each component are shown in Table 1.

Typically 10 ml of ethanol was used to prepare 100 tablets. If necessary, a small amount of the polymer base in the formulation can be dissolved in a mixed solvent of water or alcohol and used to granulate the powder.

The granules thus prepared are sufficiently dried in an oven at 60 ° C., milled evenly, and further mixed with a lubricant, magnesium stearate for molding of the formulation by post-mixing, and a bilayer tablet containing rapid release and sustained release using a rotary tablet machine. It was prepared by tableting.

<Comparative Examples 1 to 4>

Comparative Examples 1 to 4 produce tablets only in the sustained release layer except for the immediate release layer. In the western layer, aceclofenac, lactose and microcrystalline cellulose were mixed evenly to increase the fluidity of the drug. As the polymer base, hydroxypropylmethylcellulose (hydroxypropylmethylcellulose, HPMC 100,000 cps) and povidone were put into a powder mixer, mixed uniformly, and then sprayed with ethanol to prepare wet granules. The component amounts of each component are shown in Table 2.

Typically 10 ml of ethanol was used to prepare 100 tablets. If necessary, a small amount of the polymer base in the formulation can be dissolved in a mixed solvent of water or alcohol and used to granulate the powder.

The granules thus prepared are sufficiently dried in an oven at 60 ° C., milled evenly, and further mixed with a lubricant, magnesium stearate for molding of the formulation by post-mixing, and then compressed into tablets containing only a sustained release layer using a rotary tablet machine. Prepared.

Dissolution Rate Test 1

A certain amount of aceclofenac sustained-release tablet prepared in Examples and Comparative Examples was tested for dissolution by the pharmacopeias dissolution test method. PH 6.8 phosphate buffer solution was used as the eluent. The elution was performed at paddle method, eluent at 900ml, stirring speed was 50rpm, and elution temperature was 37 ± 0.5 ℃. 5 ml of samples were taken at 15, 30, 60, 90, 120, 240, 360, 480, 600, and 720 minutes, and the same amount of eluate was added. Assay conditions, the solution obtained in the above dissolution test was filtered with a 0.45㎛ membrane filter to quantify aceclofenac using HPLC. The wavelength of 254nm mobile phase was 0.16% sodium dihydrogen phosphate adjusted to pH2.5 with 0.1% phosphoric acid. The solution: methanol = (34:66) was mixed and octadecylsilylated column was used. The results of the dissolution rate test are shown in Tables 3 and 4.

Dissolution Rate Test 2

The dissolution test according to pH was carried out using the acecrofenac sustained-release tablet prepared in Examples 1 to 4 In addition, as a comparative example, a general tablet sold on the market was tested in Comparative Example 5. As the eluate, aqueous solutions of pH 1.2 (artificial gas solution) and pH 6.8 (phosphate solution) described in the Korean Pharmacopoeia Dissolution Test Method were used, respectively. The elution method was a paddle method. Elution amount was 900ml, stirring speed was 50rpm, elution temperature was performed at 37 ± 0.5 ℃. The sample collection time was based on the time that tablets generally stayed in the stomach at the time of taking the tablets, and the dissolution test was performed by successively dissolving the specimens tested at pH 1.2 for 2 hours at pH 6.8. For sample collection, 5 ml of sample was taken and the same amount of eluent was added. Assay conditions, the solution obtained in the above dissolution test was filtered with a 0.45㎛ membrane filter to quantify aceclofenac using HPLC. The wavelength of 254 nm mobile phase was 0.16% sodium dihydrogen phosphate adjusted to pH2.5 with 0.1% phosphoric acid. The mixture was methanol: (34:66) mixture and octadecylated column was used. The experimental results are shown in Table 5.

1 is a view showing the results of dissolution rate experiment 1 of Examples 1 to 4 of the present invention,

2 is a diagram illustrating the results of dissolution rate experiment 1 of Comparative Examples 1 to 4 of the present invention.

Claims (5)

In aceclofenac sustained-release tablet consisting of an immediate release layer and a sustained release layer, The immediate release layer comprises aceclofenac, a water-soluble additive poloxamer, a pH adjusting agent sodium hydrogen carbonate, a disintegrant, a filler and a lubricant, The sustained release layer comprises aceclofenac, hydroxypropylmethylcellulose as a release controlling polymer, colloidal silicon dioxide as a lipid soluble surfactant, fillers and lubricants, Aceclofenac sustained-release tablet, characterized in that the content of the sodium hydrogen carbonate is 0.25% by weight to 1% by weight relative to the total weight of aceclofenac sustained-release tablet. The aceclofenac sustained-release tablet according to claim 1, wherein the release controlling polymer is 5% by weight to 20% by weight based on the total weight of the aceclofenac sustained-release tablet. delete delete The aceclofenac sustained-release tablet according to claim 1, wherein the water-soluble additive is 0.75% to 3% by weight based on the total weight of the aceclofenac sustained-release tablet.

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