KR20060075378A - Sustained-release formulation containing felodipine - Google Patents

Abstract

The present invention relates to a felodipine sustained release formulation containing felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose, and a high viscosity polymer for controlled release, wherein the felodipine sustained release formulation of the present invention is preferred for in vivo administration. In addition to having a drug release pattern, drug release is particularly favorable in the gastric environment.

Pelodipine, Diethylene Glycol Monoethyl Ether, Low Viscosity Hydroxypropylmethylcellulose, High Viscosity Polymer for Release Control

Description

Suede-release formulation containing felodipine

Figure 1a is a graph measuring the particle size distribution of felodipine before micronization.

Figure 1b is a graph measuring the particle size distribution of felodipine after micronization.

The present invention relates to a felodipine sustained release formulation containing felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose and a high viscosity polymer for controlled release.

Pelodipine is a drug for the treatment of circulatory diseases with calcium antagonism, which has a very low solubility in water of 0.2 mg / ml. Drugs with very low solubility in water are difficult to absorb due to the slow dissolution rate, and may cause a large absorption deviation among individuals. As a method for improving the solubility of poorly soluble drugs to overcome this problem, a surfactant or a solubilizing agent may be used. Various methods are known, such as addition, particle size control of raw materials, chemical structural modification of drugs, and preparation of complexes with water-soluble substances (Drug Delivery, Hallymwon, Korea).

However, all of the above methods are not necessarily effective in solubilizing poorly soluble drugs, and solubilization methods that can be put to practical use are limited depending on the physical properties of each drug, the absorption pattern of the drug, the absorption site, and the manufacturing difficulty. In particular, even if the same series of solubilizers are used for the solubilization of certain drugs, it is well known that there are more effective solubilizers depending on the physical properties of the drugs.

On the other hand, in the treatment of the circulatory system, gastrointestinal system and chemotherapy, it is well known that it is advantageous for the administered drug to maintain a constant concentration in the blood. In particular, in the case of the treatment of circulatory diseases such as hypertension drugs, sustained release preparations have been studied in order to maintain constant blood pressure and reduce side effects due to temporary overdose of blood pressure control drugs. In general, sustained release formulations achieve the goal of controlled release by controlling the dissolution of the drug and / or the diffusion of the dissolved drug. Most of the formulations have been subjected to sustained release by preparing a matrix type formulation using a high viscosity hydrophilic polymer or poorly soluble polymer or by coating the formulation with a diffusion control film.

Therefore, when a poorly soluble drug such as felodipine is prepared as a sustained release preparation, two purposes must be achieved: solubilization of the drug and provision of sustained release. In other words, the drug must be continuously released at a constant rate while maintaining high bioavailability. In particular, the proper combination of the above two purposes is important, but if only the solubilization of the drug is focused on the release of the drug is too fast to achieve the purpose of sustained release, if the emphasis on the sustained release of the bioavailability is low (Registered in Korea Patent number 1995, 002147).

In order to achieve the above object, US Patent No. 4,803,081 uses a nonionic surfactant such as cremophore to increase the solubility of felodipine and sustained release using a hydrophilic gel-forming polymer. As a result, precipitation of the main medicine may occur, and in the case of Korean Patent Publication No. 2002-020329, a solubilizing agent of polyethylene glycol is used to increase the solubility of felodipine and simultaneously use an acrylic polymer and a higher aliphatic alcohol as a sustained release base. The disadvantage is that the process is complicated. In the Republic of Korea Patent Publication No. 2003-006994, the drug was added to the heated cetyl alcohol and then added to the swellable polymer to prepare granules. This method is difficult to control the temperature of each process step, and requires a facility that can be heated for the production. The disadvantage is that.

In addition, orally administered drugs inevitably go through the gastric environment, it is important to have an appropriate release rate in the gastrointestinal environment as well as the small intestine in order to reduce the initial burst effect and to maintain the constant absorption pattern from administration to the next administration.

Therefore, the technical problem to be achieved by the present invention is to provide a pelodipine sustained release formulation having a desirable drug release pattern when administered in vivo, and exhibits good drug release not only in the intestine environment but also in the stomach environment.

In order to achieve the above technical problem, the present invention is a felodipine (felodipine), diethyleneglycol monoethylether (diethyleneglycol monoethylether), low viscosity hydroxypropylmethylcellulose (hydroxypropylmethylcellulose) containing a high viscosity release control polymers A sustained release formulation is provided.

According to the present invention, when ethylene glycol monoethyl ether is used among various nonionic surfactants, the felodipine sustained release formulation has a good release pattern even in the above environment, and has a low viscosity hydride which plays two roles of dissolution aid and release control. It is based on the surprising fact that by using oxypropylmethylcellulose, the felodipine formulation can be designed to exhibit the desired release pattern under various drug release test conditions. However, the various components constituting the pelodipine sustained-release preparation of the present invention does not exert the above-described effects alone, but to achieve the object of the present invention organically. Therefore, even if a low viscosity hydroxypropylmethylcellulose is used instead of other low viscosity polymers that play two roles of dissolution assisting and release control, the mutual organic relationship with diethylene glycol monoethyl ether disappears and the object of the present invention is achieved. Even if low viscosity hydroxypropylmethylcellulose is used and other nonionic surfactants are used, mutual organic relations disappear, and thus the present invention does not achieve the object.

Hereinafter, the felodipine sustained-release preparation of the present invention will be described in more detail.

The present invention provides a felodipine sustained-release preparation containing felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose and a polymer for controlling the release of high viscosity in order to achieve the above technical problem.

The felodipine sustained release formulation of the present invention contains diethylene glycol monoethyl ether as a solubilizer (nonionic surfactant) for increasing the solubility of poorly soluble drugs. Non-ionic surfactant Caprylocaproyl macrogolglycerides (commercially available Labrasol ^® ), PEG hydrogenated caster oil (e.g. polyoxyl) for solubilization of poorly soluble drugs Polyoxyl 40 Hydrogenated Castor Oil (commercially available brand name Cremophor ^® RH40) and Polyoxyl 35 Hydrogenated Castor Oil (commercially available brand name Cremophor ^® ELP)], polyethylene glycol-15-hydroxystearate ( Polyethylene glycol-15-hydroxystearate, commercially available trade name Solutol ^® HS15), various polysorbates (e.g. polyoxyethylene sorbitan monolaurate (Tween 20), polyoxyethylene sorbitan monopalmitate (Tween) 40), polyoxyethylene sorbitan monostearate (Tween 60) and polyoxyethylene sorbitan monooleate (Tween) 80)], various sorbitan esters (for example, sorbitan monolaurate (Span 20), sorbitan monopalmitate (Span 40), sorbitan monooleate (Span 80)) and the like Has been used. However, felodipine sustained release preparations prepared using most nonionic surfactants except diethylene glycol monoethyl ether have very low dissolution rates in pH 1.2 buffer under conditions similar to those of the above, thus obtaining the overall desired drug release pattern. Is difficult.

The preferred diethylene glycol monoethyl ether content of the felodipine sustained release preparation of the present invention is 0.2 to 2 parts by weight with respect to 1 part by weight of felodipine. If it contains less than 0.2 parts by weight, the solubilization degree of the desired felodipine is insufficient, and if it contains more than 2 parts by weight, it is difficult to control the sustained release, so that more high-viscosity polymers for controlling the release are used, which results in a larger size of the tablet. .

The felodipine sustained release formulation of the present invention contains low viscosity hydroxypropylmethylcellulose to delay release and promote solubilization of felodipine. The low viscosity hydroxypropylmethylcellulose contained in the felodipine sustained-release preparation of the present invention was used to simultaneously play a role of dissolution aid and release control, and low viscosity hydroxypropylmethylcellulose was used to prepare a 2% aqueous solution. It means hydroxypropyl methyl cellulose in which the viscosity of the solution at 20 ° C is 20 to 150 cps, preferably hydroxypropyl methyl cellulose is 70 to 130 cps.

The content of low viscosity hydroxypropylmethylcellulose is suitably 8 to 20 parts by weight, and more preferably 10 to 15 parts by weight based on 1 part by weight of felodipine. If it contains less than 8 parts by weight of the low viscosity hydroxypropyl methyl cellulose does not exhibit a desirable dissolution aid effect, if it contains more than 20 parts by weight does not exhibit a desirable drug release pattern.

The felodipine sustained-release preparation of the present invention may optionally further contain a polymer for preparing a binder solution. The polymer for preparing the binder liquid is used to impart proper viscosity to the binder liquid when the wet granulation method is used as a process for preparing a tablet. Typically, corn starch, hydroxypropylmethylcellulose, polyvinylpyrrolidone, vinylpyrrolidone-vinylacetate copolymer, and the like may be used, but in the felodipine sustained-release preparation of the present invention, the ease of preparation of granules for tableting ( In other words, the vinylpyrrolidone-vinylacetate is considered to be coarse with the other ingredients used to control the drug release pattern, and to make the granules too rigid and too fragile so as not to break during post-mixing and transfer. Copolymers are most preferred.

The preferred content of the vinylpyrrolidone-vinylacetate copolymer used when the wet granulation method is selected for tablet manufacture is 0.5 to 4 parts by weight based on 1 part by weight of felodipine in view of the hardness of the tablet and the ease of preparation of the tableting granules. Parts by weight.

Preferred vinylpyrrolidone-vinylacetate copolymers that can be used in the felodipine sustained release formulations of the present invention are those subject to free-radical polymerization of 6 parts of vinylpyrrolidone and 4 parts of vinyl acetate. Vinylpyrrolidone-vinylacetate copolymer. Vinylpyrrolidone-vinylacetate copolymers are also commonly referred to as copovidone (Copovidone or Copovidonum), and are listed in the European Pharmacopoeia and the like under the name copovidone. The vinylpyrrolidone-vinylacetate copolymer is known to have about three times lower moisture content than polyvinylpyrrolidone, a vinylpyrrolidone-based polymer that has been conventionally used. For most sustained-release preparations, the dissolution rate or burst effect occurs over time during storage, even though the dissolution pattern is preferred at the beginning of manufacture, since the dissolution pattern is changed by the hydrophilic polymer absorbing moisture in the air during storage. to be. From this point of view, the pelodipine sustained release formulation containing the vinylpyrrolidone-vinylacetate copolymer used in the present invention may have better storage stability than the pelodipine sustained release formulation prepared using conventional polyvinylpyrrolidone. .

In the present invention, the low viscosity hydroxypropylmethylcellulose and / or vinylpyrrolidone-vinylacetate copolymer is primarily mixed with felodipine and diethylene glycol monoethyl ether so that diethylene glycol monoethyl ether, a nonionic surfactant, Helping to position around felodipine helps to ensure sufficient solubilization even with small amounts of diethylene glycol monoethyl ether.

Pelodipine sustained-release preparation of the present invention contains a high viscosity polymer for controlled release that can swell upon contact with moisture to form a gel or slow the dissolution rate of the polymer itself. The high viscosity polymer is preferably a polymer having a viscosity of 2,000 to 10,000 cps at 20 ° C. when preparing a 2% aqueous solution, and more preferably a polymer having a viscosity of 3,000 to 7,000 cps.

The content of the high-viscosity polymer for controlling release is suitably 5 to 10 parts by weight, and more preferably 6 to 8 parts by weight based on 1 part by weight of felodipine. When less than 5 parts by weight of controlled release high viscosity polymer is contained, it is difficult to achieve the desired sustained release because the release of felodipine is not controlled, and when more than 10 parts by weight of controlled release high viscosity polymer is used, the release of drug becomes too slow. It is difficult to obtain the desired elution pattern.

Release viscosity high viscosity polymers that can be used in the present invention include methyl cellulose, ethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, Polyvinylpyrrolidone, polyvinylacetate, polyalkene oxide, polyalkeneglycol, polyethylene-polypropylene polymer, polyoxyethylene-polyoxypropylene polymer, diethylaminoacetate, aminoalkyl methacrylate copolymer, sodium alginate, chitosan Or gelatin, gum or mixtures thereof may be used. Preferred high viscosity polymers for release control of the present invention are high viscosity hydroxypropylmethylcellulose.

The felodipine sustained release preparation of the present invention is also important in the content ratio of felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose and high viscosity polymer for controlled release. When the content of certain components is too much or too little for a certain component, it is difficult to obtain a desirable dissolution pattern or the weight (size) of one tablet is too large to be inconvenient to take, but also to increase the manufacturing cost. The preferred composition ratio of the felodipine sustained-release preparation of the present invention is 0.2-2 parts by weight of diethylene glycol monoethyl ether, 8-20 parts by weight of low viscosity hydroxypropylmethylcellulose and high viscosity polymer 5 for release control based on 1 part by weight of felodipine. 10 parts by weight. In a preferred embodiment of the present invention, when the polymer for preparing the binder solution contains vinylpyrrolidone-vinylacetate copolymer, 0.5-4 parts by weight of vinylpyrrolidone-vinylacetate copolymer is contained per 1 part by weight of felodipine. It is desirable to be.

Pelodipine sustained-release preparation of the present invention can be prepared in the form of tablets, capsules, granules, fine granules and the like, but particularly preferably the formulation is a tablet. In addition, the felodipine sustained-release preparation of the present invention may further include commonly used additives such as excipients, lubricants, stabilizers, flavoring agents and the like.

On the other hand the present invention (S1) dissolving the pelodipine, diethylene glycol monoethyl ether and the polymer for preparing the binder solution in an organic solvent to prepare a binder solution; And (S2) mixing the binder solution with the remaining components of low viscosity hydroxypropylmethylcellulose, high viscosity polymer for controlling release, and excipients, to prepare tableting granules. . Preferred binder polymer is a vinylpyrrolidone-vinylacetate copolymer, the advantages of using a vinylpyrrolidone-vinylacetate copolymer is as described above. This wet granulation method can be used to convert the crystalline form to amorphous form, especially when the felodipine raw material is crystalline. As an organic solvent usable for the preparation of the felodipine sustained-release preparation of the present invention, methanol, ethanol, isopropanol, acetone, methylene chloride and mixtures thereof may be used.

The present invention also comprises the steps of micronizing (S1) felodipine raw material; (S2) first mixing the finely divided felodipine with diethylene glycol monoethyl ether; And (S3) secondly mixing the primary mixture of step (S2) with low viscosity hydroxypropylmethylcellulose and a high viscosity polymer for controlling release. As a method of micronization, a sieve method or a grinding method may be used, and the sieve is performed using a generally used sieve, and instead of the sieve, a size classification method such as air current classification is used. May be used. Grinding may be a conventional mill capable of micronizing particles such as a hammer mill, a ball mill, a fluid energy mill, and the like, but is not limited thereto. The term "micronized felodipine" as used in the present invention means pelodipine in which the particles having a diameter of 90 µm or less are 70% or more.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the scope of the present invention is not limited by the following examples, and it will be apparent to those skilled in the art that various modifications may be made within the scope of the present invention.

< Preparation of Examples 1-2 and Comparative Examples 1-8 according to the kind and quantity of surfactant >

In 133 ml of ethanol, a binder solution was prepared by dissolving the felodipine, surfactant, and vinylpyrrolidone-vinylacetate copolymer by the weight shown in Table 1 below, followed by lactose, microcrystalline cellulose, and low viscosity hydroxypropylmethylcellulose. And granulation, drying (60 ° C., about 4 hours), and sizing in association with high viscosity hydroxypropylmethylcellulose, followed by mixing with magnesium stearate and hard silicic acid to tablet weight of 220 mg.

Unit: g Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 Felodipine 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Lactose 70.9 70.9 70.9 70.9 70.9 70.9 70.9 74.9 74.9 70.9 Microcrystalline cellulose 26.2 28.7 28.7 28.7 28.7 28.7 28.7 24.7 24.7 28.7 Vinylpyrrolidone-Vinyl Acetate Copolymer 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 Low Viscosity Hydroxypropyl Cellulose 67.6 67.6 67.6 67.6 67.6 67.6 67.6 67.6 67.6 67.6 High Viscosity Hydroxypropyl Cellulose 33.8 33.8 33.8 33.8 33.8 33.8 33.8 33.8 33.8 33.8 Magnesium Stearate 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Light anhydrous silicic acid 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 (Below are all kinds of surfactants) Diethylene glycol monoethyl ether 4.5 2.1 - - - - - - - - Caprylocaproyl Macrogol Glyceride - - 2.1 - - - - - - - Polyoxyl 35 Hydrogenated Castor Oil - - - 2.1 - - - - - - Polyoxyl 40 Hydrogenated Caster Oil - - - - 2.1 - - - - - Polyethylene Glycol-15-hydroxystearate - - - - - 2.1 - - - - Polyoxyethylene sorbitan monooleate - - - - - - 2.1 11.0 - - Polyoxyethylene sorbitan monolaurate - - - - - - - - 11.0 - Sodium lauryl sulfate - - - - - - - 11.0 11.0 2.1

< Pelodipine in stomach environment Evaluation of Effect of Type and Amount of Surfactant on Elution >

The dissolution test was carried out using the pelodipine-containing tablets of Examples 1 to 2 and Comparative Examples 1 to 8 prepared above (commercially available pelodypine sustained tablets (Sprendil 5 mg sustained tablets, Yuhan Corporation, Korea) as a reference). . The eluate was used as a pH 1.2 buffer described above as an environmental eluent in Korea Pharmacopoeia, and was tested at a stirring speed of 50 rpm according to the second method of the Korean Pharmacopoeia Elution Test. The results are shown in Table 2.

Elution content%                                              Reference Example 1 Example 2 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 30 minutes 0.0 0.0 1.0 1.3 0.4 0.2 0.1 0.4 0.0 0.0 0.6 60 minutes 2.2 1.9 1.1 1.9 1.0 0.6 0.4 0.6 0.0 0.0 0.6 120 minutes 5.5 4.5 2.3 3.3 1.8 1.4 0.8 1.9 0.0 0.0 1.2 240 minutes 13.1 11.9 5.7 5.8 4.0 3.3 2.1 5.0 1.6 0.0 3.1 360 minutes 20.2 18.2 10.9 6.4 4.9 4.0 3.7 7.2 4.9 1.9 5.3 480 minutes 26.6 25.6 13.3 8.7 - - - 8.5 6.0 3.8 6.7 600 minutes 27.9 31.0 15.7 9.4 - - - 10.9 8.7 5.9 7.8 720 minutes 30.1 37.4 20.9 13.6 - - - 12.8 13.1 7.9 10.8  ("-" In Comparative Examples 2, 3 and 4 is not measured)

The results in Table 2 are numerical values representing the amount of drug eluted at each time based on the total content of felodipine in the formulation. As can be seen from the results of Table 2, the pelodipine elution in the gastric environment of the pelodipine sustained release preparations prepared with all other surfactants except for the nonionic surfactant diethylene glycol monoethyl ether of the present invention is relatively It can be seen that low. As can be seen from the results of Comparative Examples 6 and 7, simply increasing the amount of surfactant does not increase the dissolution of felodipine in the gastric environment.

Preparation of Example 3 Using Undifferentiated Pelodipine

Pelodipine was micronized through sieving using a 200 mesh sieve. The particle size of felodipine before and after micronization was measured using a particle size distributor (Shimadzu SALD-2001, Japan) and the results are shown in FIGS. 1A and 1B, respectively. 5.0 g of micronized felodipine was first mixed with 4.5 g of diethylene glycol monoethyl ether, and this mixture was mixed with 70.9 g of lactose, 26.2 g of microcrystalline cellulose, 77.6 g of low viscosity hydroxypropylmethylcellulose, and 33.8 g of high viscosity hydroxypropylmethylcellulose. secondary mixing with g. Thereafter, 1.0 g of magnesium stearate and 1.0 g of hard silicic anhydride were further added and mixed homogeneously, followed by tableting. The components and contents are shown in comparison with Table 3.

< Preparation of Comparative Examples 11-12 with Different Amounts of Hydroxypropylmethylcellulose >

Comparative Examples 11 and 12 were prepared using the same method as Example 1 with the ingredients and contents shown in Table 3 below.

Unit: mg Example 1 Example 3 Comparative Example 11 Comparative Example 12                                              Felodipine 5.0 5.0 5.0 5.0 Lactose 70.9 70.9 58.9 100.9 Microcrystalline cellulose 26.2 26.2 16.2 48.7 Vinylpyrrolidone-Vinyl Acetate Copolymer 10.0 0.0 10.0 10.0 Low Viscosity Hydroxypropyl Cellulose 67.6 77.6 67.6 17.6 High Viscosity Hydroxypropyl Cellulose 33.8 33.8 55.8 33.8 Magnesium Stearate 1.0 1.0 1.0 1.0 Light anhydrous silicic acid 1.0 1.0 1.0 1.0 Diethylene glycol monoethyl ether 4.5 4.5 4.5 4.5

<Of felodipine in the gastric environment of Examples 1 and 3 and Comparative Examples 11 and 12 Dissolution Assessment >

The dissolution test of the pelodipine-containing tablets of Example 1, Example 3, Comparative Example 11 and Comparative Example 12 prepared above under similar conditions to the above environment was carried out. The eluate was used as a pH 1.2 buffer described above as the environmental eluent of the Korean Pharmacopoeia, and was tested at a stirring speed of 50 rpm in accordance with the second method of the Korean Pharmacopoeia Elution Test.

As a result of the experiment, the dissolution rate at 360 minutes after the start of Example 1 was 18.2%, whereas the dissolution rate at the same time of Example 3 using undifferentiated felodipine was 13.7%, which is relatively insufficient compared to Example 1. It can be seen that the dissolution rate is good compared to Comparative Example 1-8. The dissolution rate of Comparative Example 11 in which a large amount of high-viscosity polymer for release control was added showed a dissolution rate of 5.1% at the same time, so that the drug release in the above environment was relatively decreased, and a low amount of low-viscosity hydroxypropylmethylcellulose was added. The dissolution rate of was so fast that it was difficult to obtain a desirable drug release pattern.

< Drug Release Results of Example 1 in Various Environmental Conditions >

Dissolution test was carried out under various conditions using the tablet of Example 1 prepared above. The eluent was used as a buffer solution having the pH shown in Table 4 below. The elution medium was tested at 900 ml and the stirring speed was 50 rpm according to the 2nd method of the Korean Pharmacopoeia Elution Test. The results are summarized in Table 4 below. It was.

Elution Content% pH 1.2 pH 4.0 pH 6.8 pH 6.5 + SLS 1% ¹⁾ 30 minutes 0.0 2.3 2.4 3.1 60 minutes 1.9 4.3 3.9 6.5 120 minutes 4.5 7.3 6.3 14.1 240 minutes 11.9 12.9 10.9 32.1 360 minutes 18.2 19.1 15.6 52.9 480 minutes 25.6 23.1 19.1 72.7 600 minutes 31.0 28.9 22.5 89.5 720 minutes 37.4 32.0 25.3 102.2  1)-Elution standard of the US Pharmacopeia for Pelodipine sustained-release preparations in pH 6.5 buffer containing 1% by weight sodium lauryl sulfate.

As shown in Table 4, it can be seen that the felodipine sustained-release preparation of the present invention shows a good drug release pattern at a pH of various conditions that may occur when administered in the body.

 The present invention provides a felodipine sustained release formulation containing felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose and a high viscosity polymer for controlled release. The felodipine sustained release preparation of the present invention not only has a desirable sustained release pattern of drug release when administered in vivo, but also has good drug release, especially in the gastric environment.

Claims (6)

Pelodipine sustained release formulation containing felodipine, diethylene glycol monoethyl ether, low viscosity hydroxypropylmethylcellulose and a high viscosity polymer for controlled release. The method according to claim 1, wherein 0.2 parts by weight of diethylene glycol monoethyl ether, 8-20 parts by weight of low viscosity hydroxypropylmethylcellulose, and 5-10 parts by weight of high-viscosity polymer for release control are used based on 1 part by weight of felodipine. Pelodipine sustained-release preparation containing a weight part. The method of claim 1, wherein the sustained-release preparation is a polymer for preparing a binder solution, felodipine sustained-release preparation, characterized in that it further comprises a vinylpyrrolidone-vinylacetate copolymer. According to claim 3, wherein the vinylpyrrolidone-vinylacetate copolymer is a felodipine sustained-release preparation, characterized in that 0.5 to 4 parts by weight based on 1 part by weight of felodipine. According to claim 1, wherein the felodipine is a felodipine sustained-release preparation characterized in that the finely divided felodipine so that the particles having a diameter of 90㎛ or less of the pelodipine particles to 70% or more. According to claim 1, wherein the high-viscosity polymer for controlling the release is felodipine sustained release formulation, characterized in that the high viscosity hydroxypropylmethylcellulose.

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