KR20080010729A - Pharmaceutical composition containing vardenafil hydrochloride masked bitter and pharmaceutically acceptable salt - Google Patents

Abstract

The present invention relates to a pharmaceutical composition containing a pharmacologically active vardenafil hydrochloride and a pharmaceutically acceptable salt, with a bitter taste masked.

Description

Pharmaceutical composition containing a bitter taste masked vardenafil hydrochloride and a pharmaceutically acceptable salt.

The present invention relates to a pharmaceutical composition containing a pharmacologically active vardenafil hydrochloride and a pharmaceutically acceptable salt, with a bitter taste masked.

Vardenafil is 2- {2-ethoxy-5-[(4-ethyl-1-piperazinyl) sulfonyl] phenyl} -5-methyl-7-propylimidazo [5,1-f] [1, 2,4] triazine-4 (3H) -one, generally a cyclic guanosine-3′5′-monophosphate phosphodiesterase (cGMP PDE) inhibitor, particularly the genitourinary system, particularly erectile It is used as a therapeutic to treat dysfunction. In Korean Patent Publication No. 2004-0032865, the substance is used for the treatment of heart failure, psoriasis, female infertility, and the like. In Korea Patent No. 10-0430355, the substance is used for the treatment and erection of cardiovascular and cerebrovascular diseases. Use as a therapeutic agent for failure is disclosed.

International Publication No. WO04 / 006894 discloses a coating tablet containing vardenafil hydrochloride. The prior art is a solid tablet form to be taken with a large amount of water is a problem that is difficult to take the elderly or patients with weak swallowing ability.

U. S. Patent No. 6,740, 306 discloses a composition for non-administering a cGMP PDE inhibitor. The prior art has a disadvantage in that the compliance of the patient is lowered due to the rejection of nasal administration. The liquid formulation may be selected as a method for improving the compliance of the patients, but in the case of the liquid, it is difficult to take and carry the correct medicine dose, and there are problems such as stability of the drug in an aqueous solution.

The development of oral dissolving tablets to solve the above problems has been actively made recently. Oral dissolving tablets disintegrate quickly even by a small amount of saliva in the oral cavity, so that they can be taken without water, and the effect of improving patient compliance is excellent and solid. Since it is in the form of a tablet, the precise dosage of the drug and the drug stability in the formulation is excellent, there are advantages that can be easily carried. However, vardenafil is a drug that has a very bitter taste even at low concentrations, and has a limitation in that it is developed as a dosage form disintegrated in the oral cavity without water due to this property. That is, even if fasteners are prepared by adding sweeteners such as aspartame, acesulfame, and sucralose, which are common methods of masking bitterness (more than 100 times sweeter than sugar), due to the strong sweetness of the sweeteners, The bitter taste is felt to be shielded, but as the drug melts in the oral cavity, its own bitter taste is expressed, so effective shielding is not achieved.

Various methods for masking the bitter taste of drugs are known, and Korean Patent Publication Nos. 2001-0014398 and 2004-0012696 disclose methods for masking bitter taste by adding cyclodextrin to a bitter drug. However, in order to partially reduce the bitter taste of the drug by applying the prior art, it is virtually impossible to develop oral fast disintegrating tablets without water because very large amounts of excipients must be used.

Korean Patent Publication No. 2002-0074822 discloses a method for masking bitter taste by preparing a solid dispersion of a bitter drug and dextrin. However, the prior art has a disadvantage in that the manufacturing process is complicated and the development of Sokbung tablet is difficult due to the large amount of excipients used.

Korean Patent Publication Nos. 1991-0004180, 2001-0023384, and 2002-0002321 disclose methods for masking unpleasant tastes by coating drug particles of bitter taste with cellulose, lipids, or polymers. However, the prior art may have an unpleasant taste of the drug due to the partial cracking of the coating portion generated during tableting, the manufacturing process is complicated, and the drug release and absorption rate is difficult to control.

International Patent Application Publication No. WO06 / 055142 discloses a method for preparing microparticles by coating drug particles such as vardenafil with a mixture of a polymer insoluble in water and a porous forming material soluble in gastric juice, and applying the same to oral disintegrating tablets. However, the bitter taste of the vardenafil itself is completely shielded by partial cracking of the shielding membrane generated during tableting of the oral disintegration in the oral disintegration of Sokbung tablets due to the effect of insoluble microparticles in the prior art water, and also during tableting. It may not be possible.

Intraoral application of vardenafil hydrochloride or pharmaceutically acceptable salts to enhance patient compliance should be preceded by drug-specific bitterness masking. To date, there has been no experimental demonstration of taste taste through the composition of vardenafil or hydrochloric acid vardenafil, and the application of techniques such as coating or encapsulating drug particles with an insoluble substance, which is a conventional technique disclosed for masking bitter taste, is applied. Because of the difficulty of effective bitterness shielding, there was no real oral fast disintegrating tablet.

Therefore, even after the drug is completely dissolved, there is a need for a method that can mask the bitter taste.

The present inventors aim to provide a composition that can mask the bitter taste even after the drug is completely dissolved in water in order to change the taste characteristics of vardenafil. It is also an object of the present invention to provide oral quick disintegrating tablet without the water of vardenafil through bitterness shielding.

The present invention relates to a pharmaceutical composition containing a pharmacologically active vardenafil hydrochloride and a pharmaceutically acceptable salt, with a bitter taste masked.

In the present invention, in order to mask the bitter taste generated when dissolving the pharmacologically active vardenafil in the oral cavity, a composition of the vardenafil and pharmaceutically acceptable excipients was prepared. The compositions were prepared using a variety of pharmaceutically acceptable methods and evaluated the bitterness masking effect of the drug expressed as the composition dissolved when the compositions were applied orally. Surprisingly, it has been found that the compositions of vardenafil and alkaline substances in these compositions provide excellent masking of the inherent bitter taste.

The pharmacologically active substance used in the present invention can be used as an antidepressant, migraine, antiseptic, antihypertensive, analgesic, diuretic, antiulcer, antithrombotic, chemotherapeutic, diabetic, etc. Preferably, it can be applied to the treatment for erectile dysfunction.

The erectile dysfunction treatment agent that can be used pharmacologically is vardenafil, sildenafil, tadanafil, apomorphine and the like; Antidepressants are paroxetine, fluoxetine, setraline and the like; Migraine treatments are sumatriptan, ergotamine, and the like; Anti-nausea agents are meclazine, ondansetron, granistron, lamosetron, trocetolone and the like; Antihypertensive agents are propranolol, amlodipine, felodipine, nifedipine, captopril, ramipril, athenol, diltiazem, and the like; Analgesics are acetaminophen, aspirin and the like; Diuretics are furosemide, spironolactone and the like; Anti-ulcer agents are cimetidine, ranitidine, pamotidine, omeprazole, lansoprazole and the like; Antithrombotic agents are sulfinpyrazone, dipyridamole, ticlopidine and the like; Chemotherapeutic agents are cefacller, bacampicillin, sulfamemethazole, rifampicin and the like; Antidiabetic agents are acarbose, glyclazide, glyphided and the like.

The present invention relates to a pharmaceutical composition characterized by masking bitterness by preparing granules or mixtures containing the pharmacologically active vardenafil hydrochloride and a pharmaceutically acceptable salt and an alkaline substance.

Alkaline materials that can be used for the bitterness masking can be classified into inorganic materials and organic materials, and inorganic alkali materials include sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, magnesium carbonate, sodium citrate, sodium stannate, and phosphoric acid. Sodium hydrogen, sodium phosphate, potassium phosphate, magnesium trisilicate, aluminum compounds and the like; Alkanol amines such as L-arginine, lysine, histidine and monoethanolamine, triethanolamine, etc. which are monomolecular forms among organic alkaline substances can be used; Among the organic alkali materials, chitosan, polyarginine copolymer, polylysine copolymer, and alkaline methacrylate copolymer of Eudragit series may be used. It is preferable to use sodium bicarbonate, L-arginine and Eudragit EPO among the alkaline substances. In addition, excipients used for the atomization can be used alone or in combination of one or more.

In the present invention, when the vardenafil hydrochloride or the pharmaceutically acceptable salt is contacted with an alkaline substance with or without water or an organic solvent, a change in complete or partial bitter taste occurs and the aesthetics of the vardenafil occurs. Do not escape.

In the present invention, the alkaline substance in the monomolecular form is used in an amount of 0.1 to 5 equivalents based on 1 equivalent of vardenafil hydrochloride or a pharmaceutically acceptable salt, and in an alkaline polymer form, 0.1 to 5 weights based on 1 weight of vardenafil.

In the present invention, the pharmaceutical composition of vardenafil and an alkaline substance is used in a homogeneous combination with or without a solvent. As the usable solvent, water or an organic solvent may be used as a single solvent or a mixed solvent, and water may be preferably used. As a method of removing the solvent used, a conventional method which is used in a pharmaceutical form may be used. In addition, a solid pharmaceutical composition may be prepared by using a single or combined preparation method with or without a solvent.

The bitter taste masking pharmaceutical composition may be used 0.1 to 50% by weight of the total weight of the tablet, preferably 0.5 to 30% by weight may be used, in addition to the pharmaceutically acceptable excipient may be further included.

Therefore, the present invention is a pharmaceutical composition characterized in that oral disintegrating tablet with a bitter taste containing at least one of the pharmacologically active vardenafil hydrochloride and a pharmaceutically acceptable salt and an alkaline substance and a pharmaceutically acceptable excipient, respectively. It is about.

The pharmaceutically acceptable excipients include disintegrants, binders, diluents, sweetening agents, organic acids, lubricants, flavors, and preservatives. At least one selected from preservatives, coloring agents, surfactants, and the like may be used, and an excipient having a combination of the above functions may be used. Excipients that have fast disintegrating properties when applied to tablets because they have all the properties of a binder and a disintegrant or a drip and a disintegrant, such as StarLac, Pharmaburst or Pharmagum 1 or more types can be used among them. And at least one selected from sodium croscamelloose, sodium starch glycolic acid, cross-linked polyvinylpyrrolidone, gelatinized starch, low-substituted hydroxypropyl cellulose, sorbitol, mannitol, erythritol, and the like as a disintegrant; As the binder, one or more selected from polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, dicalcium phosphate, sodium alginate and the like can be used; As the diluent, one or more selected from lactose, dextrose, microcrystalline cellulose, starch and the like can be used; Flavors include orange flavor powder, grape flavor powder, apple flavor powder, lemon flavor powder, strawberry flavor powder, cherry flavor powder, pineapple flavor powder, banana flavor powder, tutti fruit flavor powder, blueberry flavor powder, peppermint powder, cocoa powder, At least one selected from milk flavor powder and the like can be used; As the sweetening agent, at least one selected from dextrose, xylitol, aspartame, acesulfame, ammonium glycyrrhinate, saccharin, sucralose, citric acid and the like can be used; As the lubricant, one or more selected from magnesium stearate, talc, light silicic anhydride, sucrose fatty acid ester and the like can be used; As the pigment, one or more selected from water-soluble and tar dyes can be used; Preservatives may be used one or more selected from benzoic acid, methyl paraben, ethyl paraben, propyl paraben and the like, but is not limited thereto.

As the dosage form of the pharmaceutical formulation composition of the present invention, it may be used as an oral solid preparation such as tablet, granule or powder. Preferably, oral quick disintegrating tablets may be selected from tablets for oral administration.

The prepared formulation composition may be administered from 5 mg up to 20 mg per day for the treatment of erectile dysfunction as the content of vardenafil.

Hereinafter, the configuration and operation of the present invention will be described in detail with reference to the following examples, but the present invention is not limited thereto.

Example  1-5

For Example 1-5, equivalent amounts of 1, 1.5, 2, 2.25, and 2.5 equivalents of sodium bicarbonate to 1 equivalent of vardenafil hydrochloride and sodium bicarbonate in the composition of Table 1 are given in a standard mesh of 30 mesh. It was sieved through and mixed uniformly and placed in a container for kneading. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder.

  Compositions of Examples 1-5 Furtherance Volume (mg) Example 1 Example 2 Example 3 Example 4 Example 5 Vardenafil Hydrochloride 100 100 100 100 100 Sodium bicarbonate 14.5 21.8 29.0 32.6 36.3

Example  6-10

For Example 6-10, the equivalent amount corresponding to 1, 1.5, 2, 2.25, and 2.5 equivalents of L-arginine with respect to 1 equivalent of vardenafil hydrochloride and L-arginine hydrochloride vardenafil hydrochloride in the composition of Table 2 for a standard mesh of 30 mesh Sieve and mixed uniformly to put in an associated container. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder.

  Compositions of Examples 6-10 Furtherance Volume (mg) Example 6 Example 7 Example 8 Example 9 Example 10 Vardenafil Hydrochloride 100 100 100 100 100 L-arginine 30.1 45.1 60.1 67.6 75.2

Example  11-14

For the example 11-14, the amount of vadenafil hydrochloride, L-arginine, and sodium bicarbonate in the composition of Table 3 is 1,1.5 equivalents of L-arginine and sodium bicarbonate, respectively, based on 1 equivalent of vardenafil hydrochloride, 30 mesh It was sieved through a standard network of and mixed uniformly and placed in a fed container. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder.

  Compositions of Examples 11-14 Furtherance Volume (mg) Example 11 Example 12 Example 13 Example 14 Vardenafil Hydrochloride 100 100 100 100 L-arginine 30.08 45.12 30.08 45.12 Sodium bicarbonate 14.51 14.51 21.77 21.77

Example  15-16

Vardenafil hydrochloride and L-arginine were sieved with an equivalent amount of 1 and 2 equivalents of L-arginine to 1 equivalent of vardenafil hydrochloride with a standard mesh of 60 mesh and uniformly mixed to obtain a white or pale white powder.

   Compositions of Examples 15-16 Furtherance Volume (mg) Example 15 Example 16 Vardenafil Hydrochloride 100 100 L-arginine 30.1 60.1

Example  17-18

For Examples 17-18, the amount corresponding to the weight of Eudragit ipio 1, 2 with respect to 1 weight of vardenafil hydrochloride and Eudragit EPO in the composition of the following Table 5 with respect to 1 weight of vardenafil hydrochloride is 30 mesh It was sieved through a standard network and mixed uniformly and placed in a fed container. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder.

  Compositions of Examples 17-18 Furtherance Volume (mg) Example 17 Example 18 Vardenafil Hydrochloride 100 100 Eudragit EPO 100 200

Example  19-26

For Examples 19-26, 1, 5 hydroxypropylbetacyclodextrin was contained per 1 weight of the composition of Examples 2, 3, 7 and 8 in the compositions of Table 6 below. It was uniformly milled for 15 minutes and sieved through a 50 mesh standard net to obtain a white or pale yellow powder.

  Compositions of Examples 19-26 Furtherance Volume (mg) Example 19 Example 20 Example 21 Example 22 Example 23 Example 24 Example 25 Example 26 Hydroxypropyl beta cyclodextrin 100 500 100 500 100 500 100 500 Composition of Example 2 100 - - - - - - - - 100 - - - - - - Composition of Example 3 - - 100 - - - - - - - - 100 - - - - Composition of Example 7 - - - - 100 - - - - - - - - 100 - - Composition of Example 8 - - - - - - 100 - - - - - - - - 100

Example  27-30

For Examples 27 to 28, the composition of Example 18, mannitol, Pharmaburst B2, crosslinked polyvinylpyrrolidone, sucralose, orange flavor powder, and citric acid equivalent in The mixture was sieved through a standard mesh of 30 mesh, added to the corresponding amount of magnesium stearate, mixed again, and the tablets were compression molded in a conventional manner. For Examples 29 to 30, the composition of Example 3, mannitol, Pharmaburst ratio 2, crosslinked polyvinylpyrrolidone, sucralose, grape flavor powder, citric acid equivalent amount were mixed and sieved through a 30 mesh standard network. A corresponding amount of magnesium stearate was added thereto, mixed again, and the tablets were compression molded in a conventional manner. Through this, oral or swallowed without water and very quickly disintegrated in the oral preparations do not have a bitter taste.

  Pharmaceutical Compositions of Examples 27-30 Furtherance Amount of pharmaceutical composition per tablet (mg) Example 27 Example 28 Example 29 Example 30 Composition of Example 18 (20 mg as vardenafil) 71.12 71.12 - - Composition of Example 3 (20 mg as vardenafil) - - 30.58 30.58 Mannitol 279.35 - 239.89 - Pharmaburst B2 - 279.35 - 239.89 Crosslinked polyvinylpyrrolidone 11.93 11.93 11.93 11.93 Magnesium stearate 5.7 5.7 5.7 5.7 Orange Flavor Powder 7.6 7.6 - - Grape flavor powder - - 7.6 7.6 Sucralose 2 2 2 2 Citric acid 2.3 2.3 2.3 2.3

  * Pharma Burst B2: SPI Pharma's fast disintegrating excipient

Example  31-34

For Examples 31 to 32, 30 mesh of the composition of Example 9, Pharmaburst B1, crosslinked polyvinylpyrrolidone, sucralose, flavor powder, corresponding to It was sieved through a standard network, added to the corresponding amount of magnesium stearate, mixed again, and the tablets were compression molded in a conventional manner. For Examples 33 to 34, the composition of Example 9, StarLac, crosslinked polyvinylpyrrolidone, sucralose, and a corresponding amount of fragrance powder were mixed and sieved through a standard mesh of 30 mesh and magnesium stearate Rate equivalents were added and mixed again and the tablets compressed by conventional methods. Through this, the oral quick disintegrating tablet was prepared without being bitter even if eaten or swallowed without disintegration in the mouth very quickly.

  Pharmaceutical Compositions of Examples 31-34 Furtherance Amount of pharmaceutical composition per tablet (mg) Example 31 Example 32 Example 33 Example 34 Composition of Example 9 (20 mg as vardenafil) 39.73 39.73 39.73 39.73 Pharmaburst B1 313.04 313.04 - - StarLac - - 232.93 233.63 Crosslinked polyvinylpyrrolidone 11.93 11.93 16.4 16.4 Magnesium stearate 5.7 5.7 5.69 5.69 Cherry Flavor Powder 7.6 - - - Lemon Flavor Powder - 7.6 - - Peppermint Powder - - 3.25 3.25 Sucralose 2 2 2 1.3

* Pharma Burst B1: Rapid disintegrating excipient of SPI Pharma Co., Ltd.

* Starac: The fast disintegrating excipient of the Roquette company

Comparative example  1-3

For Comparative Example 1-3, 1 equivalent of sodium hydrochloride, acesulfame, and aspartame 2 equivalents of 1 equivalent of vardenafil hydrochloride in the composition of Table 9 was sieved through a standard mesh of 30 mesh and uniformly mixed. In a container. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder form.

  Compositions of Comparative Examples 1-3 Furtherance Volume (mg) Comparative Example 1 Comparative Example 2 Comparative Example 3 Vardenafil Hydrochloride 100 100 100 Sodium hydrochloride 20.18 - - Acesulfame - 101.64 - Aspartame - - 69.50

Comparative example  4-6

For Comparative Example 4-6, hydroxypropylbetacyclodextrin (HP--CD), ILP 64 (IRP 64), and ILP 69 (IRP 69), respectively, were added to 1 weight of vardenafil hydrochloride in the composition of Table 10 below. The corresponding amount corresponding to the weight was sieved through a standard mesh of 30 mesh and uniformly mixed and placed in an associated container. 200 uL of water was added dropwise and uniformly combined for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white or yellowish white powder.

  Composition of Comparative Example 4-6 Furtherance Volume (mg) Comparative Example 4 Comparative Example 5 Comparative Example 6 Vardenafil Hydrochloride 100 100 100 Hydroxypropylbetacyclodextrin 200 - - IRP 64 - 200 - ILP 69 - - 200

Comparative example  7-8

For Comparative Example 7-8, the amount of vardenafil hydrochloride and gluconic acid hydrochloride equivalent to 1, 2 equivalents of gluconic acid with respect to 1 equivalent of vardenafil hydrochloride was sieved through a standard mesh of 30 mesh and uniformly It was mixed and placed in a container for association. 200 uL of water was slowly added dropwise thereto for 10 minutes, which was dried at 45 ° C. for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white powder.

  Composition of Comparative Example 7-8 Furtherance Volume (mg) Comparative Example 7 Comparative Example 8 Vardenafil Hydrochloride 100 100 Gluconic Acid 33.87 67.74

Comparative example  9-10

For Comparative Example 9-10, vardenafil hydrochloride and carrageenan hydrochloride in the composition of Table 12 were sieved with a standard mesh of 30 mesh, corresponding to 1, 2 weight of carrageenan relative to 1 weight of vardenafil hydrochloride and uniform. Mixed into a container for association. This was combined for 10 minutes while slowly adding 200 uL of water, which was dried at 45 ° C for 6 hours. The dried product was ground and passed through a standard mesh of 50 mesh to obtain a white or yellowish white powder.

  Composition of Comparative Example 9-10 Furtherance Volume (mg) Comparative Example 9 Comparative Example 10 Vardenafil Hydrochloride 100 100 Carrageenan 100 200

Experimental Example  1: comparison of taste

The pre-prepared compositions were taken 20 mg each as vardenafil without the use of any excipients, water or other solvents, allowing each 10 subjects to taste for 3 minutes in the mouth of the subjects. Vardenafil is very bitter even with a small amount of raw material when it is tasted due to the nature of the material itself, and it makes the bitter taste hard to tolerate with time.

  Taste of Vardenafil Composition Furtherance Taste just after intraoral application Taste after 1 minute Comparative Example 1 Very bitter taste Very bitter taste Comparative Example 2 bitter Very bitter taste Comparative Example 3 bitter Very bitter taste Comparative Example 4 Very bitter taste Very bitter taste Comparative Example 5 Very bitter taste Very bitter taste Comparative Example 6 Very bitter taste Very bitter taste Comparative Example 8 Very bitter taste Very bitter taste Comparative Example 10 Very bitter taste Very bitter taste Example 3 Weak bitter taste bitter Example 8 Senseless Very mild bitter taste Example 9 Senseless Senseless Example 12 Weak bitter taste bitter Example 14 Weak bitter taste Weak bitter taste Example 16 Weak bitter taste Weak bitter taste Example 18 Senseless Senseless Example 22 Senseless Very mild bitter taste Example 24 Senseless Senseless

As a result of the experiment, as shown in Table 13, all other types of excipients except L-arginine, sodium hydrogen carbonate, and Eudragit ipio when preparing a combined or mixed composition using only one vardenafil and one excipient, all have the bitter taste of vardenafil. There was no shielding at all and the subjects expressed strong rejection. However, when using two or more types of excipients that mask the bitterness of vardenafil and other excipients, it was confirmed that the bitterness is shielded. The composition prepared by the examples of the present invention surprisingly tasted the unique bitterness attributable to vardenafil and subjects showed little taste rejection. In addition, it was confirmed that even a uniform mixing of vardenafil and L-arginine can achieve a breakthrough bitter taste. And it was confirmed that the composition prepared according to the embodiment of the present invention is no foreign matter in the entire example except for the unpleasant foreign matter caused by Eudragit of Example 18. Therefore, it was confirmed that the present invention is limited to the purpose of treating erectile dysfunction for oral disintegration that can be eaten without water.

Experimental Example  2 : Disintegrate  And Intraoral Disintegration  Time comparison

The disintegration was measured according to the pharmacopeia disintegration test method of the compositions prepared in Tables 7 to 8. In addition, the tablets were administered to each of the 10 subjects orally to evaluate the time the tablets are completely released in the oral cavity.

As a result of the experiment, all the tablets prepared as shown in Table 14 showed excellent disintegration, and in particular, the measurement of disintegration of tablets using Pharmaburst series was excellent.

  Disintegration of Vardenafil Oral Quick Release Tablet Composition Disintegration Measurement Intraoral Disintegration Time Example 27 68 seconds 60 seconds Example 30 32 sec 50 seconds Example 32 30 sec 40 seconds Example 34 38 sec 40 seconds

The present invention has led to the discovery of compositions of vardenafil masked with bitterness and pharmaceutical compositions containing them.

By applying the composition masking the bitter taste of the present invention, a composition containing a conventional sweetener or flavor, a cyclodextrin additive, a solid dispersion using dextrin, a thick taste resulting from other substances such as coating of an insoluble substance, The drug's bitterness is surprising even if the drug is dissolved in the oral cavity, rather than masking the bitter taste of the drug, enclosing the drug particles using a large amount of excipients, or covering the drug particles themselves with an insoluble substance. A totally new vardenafil beautification has been made possible with a woolly shield.

Therefore, the composition of the vardenafil and the alkaline substance of the present invention can be said to be suitable for fast disintegrating tablets for oral fast disintegrating tablets, especially erectile dysfunction treatment for eating without water.

In addition, it was confirmed that the specific effect on the atomization can be obtained by homogeneously mixing not only the associated composition but also vardenafil and the alkaline substance.

Claims (5)

A bitter taste masking pharmaceutical composition comprising vardenafil hydrochloride or a pharmaceutically acceptable salt thereof as an active ingredient and at least one pharmaceutically acceptable alkaline substance. 2. A bitter taste masked pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is oral fast disintegrating tablet. The alkaline material according to claim 1 or 2, wherein the alkaline material is sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, magnesium carbonate, sodium citrate, sodium stannate, sodium hydrogen phosphate, sodium phosphate, potassium phosphate, magnesium trisilicate, aluminum At least one selected from compounds, L-arginine, lysine, histidine, alkanol amines, chitosan, polyarginine copolymers, polylysine copolymers and alkaline methacrylate copolymers (trade name; Eudragit Ipio) A bitter taste masked pharmaceutical composition characterized by. 4. A bitter taste masked pharmaceutical composition according to claim 3, wherein the alkaline substance is sodium bicarbonate, L-arginine or an alkaline methacrylate copolymer (trade name; Eudragit Ipio). The alkaline substance according to claim 1 or 2, wherein the alkaline substance contains 0.1 to 5 equivalents to 1 equivalent of vardenafil hydrochloride or a pharmaceutically acceptable salt thereof, and 0.1 to 1 weight of vardenafil when in the form of a polymer. Bitter taste masked pharmaceutical composition, characterized in that it contains from 5 to 5.