WO2014092358A1

WO2014092358A1 - Chewable tablet comprising a phosphodiesterase-5 inhibitor

Info

Publication number: WO2014092358A1
Application number: PCT/KR2013/010739
Authority: WO
Inventors: Yong Il Kim; Ki Woo Jeong; Hayoung Jeong; Kyeong Soo Kim; Jae Hyun Park; Jong Soo Woo
Original assignee: Hanmi Pharmaceutical Co Ltd; Hanmi Pharmaceutical Industries Co Ltd
Current assignee: Hanmi Pharmaceutical Co Ltd; Hanmi Pharmaceutical Industries Co Ltd
Priority date: 2012-12-14
Filing date: 2013-11-25
Publication date: 2014-06-19
Anticipated expiration: 2015-06-14
Also published as: AR093707A1; KR101953735B1; KR20140077658A; TW201427721A

Abstract

The present invention provides a chewable tablet comprising a phosphodiesterase-5 (PDE-5) inhibitor and a disintegrant having a swelling coefficient ranging from 4 to 8 L/kg which can be taken without water, causing no feeling of irritation in the oral cavity, and thus can improve compliance and patient satisfaction; it also exhibits a rapid disintegration in the oral cavity, therefore can be useful as a therapeutic agent in the treatment of human male erectile dysfunction.

Description

DESCRIPTION

CHEWABLE TABLET COMPRISING A PHOSPHODIESTERASES INHIBITOR

FIELD OF THE INVENTION

The present invention relates to a chewable tablet comprising a phosphodiesterase- 5 (PDE-5) inhibitor or a pharmaceutically acceptable salt thereof and a disintegrant having controlled swelling coefficient.

BACKGROUND OF THE INVENTION Erectile dysfunction is a medical condition of inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse 25% or more of the time. This prevalent type of sexual dysfunction is caused by reduced blood flow to corpus cavernosum, or failure to build up intracavernous pressure even if the blood flow is sufficient because the supplied blood is not trapped by corpus cavernosum but flows back to vein due to various reasons. Erectile dysfunction is a very common condition which may occur at any age, especially occurs more frequently in men over the age of 55. Generally, it is known that approximately 5 to 10% of adult males suffer from erectile dysfunction.

There is a number of PDE-5 inhibitors developed, which are known for treatment of erectile dysfunction, as a selective inhibitor of cyclic guanosine 3 ',5 '-monophosphate phosphodiesterase type 5 (cGMP PDE-5), including Vardenafil, 1 -[[3-( 1 ,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5, 1 - fj[ 1 ,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-4-ethyl, C₂₃H₃2N₆O₄S); Sildenafil, l-[[3-(6,7-dihydro-l-methyl-7-oxo-3-propyl-lH-pyrazolo[4,3- d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine, C22H30N6O4S Tadalafil, (6 ,12aR)-6-(l,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2- methyl-pyrazino[ 1 ' ,2 ' : 1 , 6]pyrido[3 ,4-b] indol- 1 ,4-dione, C₂₂H 1₉N₃0₄; Udenafil, C25H₃₆N₆0₄S. Accordingly, the use of Vardenafil, Sildenafil, Tadalafil and Udenafil for treating erectile dysfunction is disclosed in KR Pat. Nos. 0430355, 0262926, 0357411 and 0353014, respectively.

Most of the PDE-5 inhibitors are available in tablet form for oral administration. Vardenafil is sold under the name Levitra^® by Bayer; Sildenafil is sold under the name Viagra^® by Pfizer; and Tadalafil is sold under the name Cialis^® by Lilly. Also, Udenafil is sold under the name Zydena^® by Dong-A Pharmaceutical. The average onset time of these drugs is approximately 60 to 90 minutes, causing great inconvenience to the patients because they have to calculate the time and take the drug in advance of having intercourse. Also, these drugs are in the form of tablet which causes some inconvenience because they must be taken with water. Therefore, there is a strong demand for a research on development of a PDE-5 inhibitor formulation that rapidly disintegrates in the oral cavity which can be taken without water.

Further, PDE-5 inhibitors used for treating human male erectile dysfunction, so called a happy drug, can improve patients' quality of life. Thus, therapeutic effect as well as factors including compliance and satisfaction level of patients must be considered during the development of the formulation. Conventional orally disintegrating tablets or chewable tablets showed a fast disintegration time, however, it was difficult to completely eliminate the unpleasant gritty or sandy sensation in the mouth when the tablet was released in the mouth.

Therefore, the present inventors have endeavored to improve compliance and patient satisfaction of the PDE-5 inhibitor formulation, which can be taken without water, causing no feeling of irritation in the oral cavity with rapid onset of therapeutic effect due to fast-disintegrating property, and have accomplished the present invention.

SUMMARY OF THE INVENTION

Therefore, it is an object of the present invention to provide a chewable tablet comprising a phosphodiesterase-5 inhibitor which rapidly disintegrates in the oral cavity without causing feeling of irritation for convenient administration.

In accordance with one object of the present invention, there is provided a chewable tablet comprising a phosphodiesterase-5 inhibitor or a pharmaceutically acceptable salt thereof; and a disintegrant having a swelling coefficient ranging from 4 to 8 L/kg.

Also, there is provided a chewable tablet which further comprising sugar, sugar alcohol or a mixture thereof.

The chewable tablet comprising PDE-5 inhibitor in accordance with the present invention can be taken without water, causing no feeling of irritation in the oral cavity, and thus can improve compliance and patient satisfaction; it also exhibits a rapid disintegration in the oral cavity, therefore can be useful as a therapeutic agent in the treatment of human male erectile dysfunction.

DETAILED DESCRIPTION OF THE INVENTION

The chewable tablet in accordance with the present invention comprising a PDE-5 inhibitor or a pharmaceutically acceptable salt thereof as an active ingredient together with a disintegrant having controlled swelling coefficient has an advantage of rapid onset time of therapeutic effect which rapidly disintegrates in the oral cavity without causing feeling of irritation, and thus shows a high level of patient satisfaction.

The active ingredient of the chewable tablet of the present invention may be a PDE-5 inhibitor including Vardenafil, Sildenafil, Tadalafi, Udenafil or a pharmaceutically acceptable salt thereof, preferably Sildenafil free base.

The PDE-5 inhibitor or a pharmaceutically acceptable salt thereof may be employed in an amount ranging from 5 to 100 mg per tablet, 0.1 to 80% by weight, preferably 1 to 70% by weight, based on the total weight of the formulation.

The disintegrant is an essential ingredient used for rapid disintegration of the chewable tablet of the present invention, which may be employed in an amount ranging from 1.5 to 15% by weight, based on the total weight of the formulation. If the amount of the disintegrant exceeds 15%, tabletting properties of the formulation deteriorate and it becomes difficult to maintain the shape of the tablet. On the contrary, if the amount used is less than 1.5%, it does not act as a disintegrant effectively, causing delayed disintegration of the tablet.

There are three major mechanisms how disintegrant disintegrate tablets:

(1) Swelling: particles of a disintegrant swell on coming in contact with a medium such as saliva and a swelling force of a disintegrant develops which leads to break-up the tablet. The examples of this type of disintegrants are sodium croscarboxymethylcellulose, sodium starch glycolate, pregelatinized starch, etc;

(2) Porosity and capillary action: when the tablet was put into a medium such as saliva, the medium penetrates into the tablet through capillary action causing the tablet to break apart. The examples of this type of disintegrants are corn starch, sodium alginate, etc. ; and

(3) Deformation: particles of a disintegrant get deformed during tablet compression and the particles recover their normal structure when they come in contact with a medium such as saliva. The examples of this type of disintegrants are crospovidone, starch grain, etc. (see John C Carter, The role of disintegrants in solid oral dosage manufacturing, Carter Pharmaceutical Consulting, Inc.).

The disintegrants are generally water-insoluble, and thus, they are largely responsible for causing unpleasant feeling of irritation when taken orally as a chewable tablet. Hence, the diameter and swelling coefficient of disintegrants are considered as two critical factors which affect feeling of irritation of a chewable tablet. An increase in the diameter of a disintegrant causes an increase in the feeling of irritation; and, similarly, when the swelling coefficient of a disintegrant is increased, so is the feeling of irritation. However, if the swelling coefficient of a disintegrant is too small, the disintegrant may not effectively serve its original purpose and cause bigger particles to remain in the mouth, thereby resulting greater feeling of irritation. It is essential to use disintegrants having suitable diameters and swelling coefficients in the preparation of a chewable tablet with fast-disintegrating properties without causing too much feeling of irritation in the oral cavity.

In the present invention, the swelling coefficient of the disintegrant may be in the range of 2 to 12 L/kg, preferably 4 to 8 L/kg. Also, the diameter of the disintegrant may vary depending on the swelling coefficient as described above, for example, in the range of 5 to 250 μηι.

In accordance with one embodiment of the present invention, the disintegrants employable include the following examples in said range as described above: Polyplasdone XL- 10 (crospovidone) (5.4 L/kg), Polypladone XL (crospovidone) (5.8 L/kg), Kollidon CL (crospovidone) (4.3 L/kg), Kollidon CL-M (crospovidone) (7.2 L/kg), Ac-Di-Sol (sodium croscarboxymethylcellulose) (13.5 L/kg), and StarCap 1500 (corn starch) (1.8 L/kg).

However, the disintegrants employable in the present invention are not limited to the said particular examples; and any disintegrant having suitable diameter and swelling coefficient may be used in the present invention.

The chewable tablet of the present invention may further comprise sugar, sugar alcohol or a mixture thereof. Said sugar, sugar alcohol or a mixture thereof is considered as an important ingredient because it gives sweet taste in the mouth and affects solubility, texture, etc, and thus, it should possess sweet flavor as well as good solubility. Examples of the sugar in the present invention include lactose, glucose, sucrose, fructose, levulose, maltodextrin, palatinose and the like. Examples of the sugar alcohol in the present invention include mannitol, sorbitol, xylitol, erythritol and the like. The porous sugar or sugar alcohol is prepared by spray drying, etc. is preferable to increase solubility thereof in the oral cavity. In one embodiment of the present invention, spray dried mannitol (Mannitol SD 200) is used. In the present invention, the sugar, sugar alcohol or a mixture thereof may be employed in an amount ranging from 10 to 98% by weight, preferably 20 to 95% by weight, based on the total weight of the formulation. If the amount employed is less than 10%, then the sweet taste and texture in the oral cavity may deteriorate.

In addition to the ingredient explained above, the composition in accordance with the present invention may further comprise one or more of 9

pharmaceutically acceptable additives, for example, those selected from the group consisting of a flavoring agent, a coloring agent, a sweetening agent and a lubricant.

The flavoring agent may be employed to improve the taste by giving a good flavor when the chewable tablet is administered orally. Specific examples may include peppermint flavor, spearmint flavor, various fruit flavors, etc.

The coloring agent may be employed to improve the appearance of the chewable tablet. Examples of the coloring agent include Green No. 3, Red No. 2, Red No. 3, Blue No. 1, Blue No. 2, Yellow No. 4, Yellow No. 5, caramel, titanium dioxide, ferric oxide or other natural coloring agents.

The sweetening agent may be employed to give a sweet flavor and soften the texture for improving patient compliance. Specific examples may include stevioside, xylitol, sucralose, aspartame, acesulfame potassium, sucrose, erythritol and a mixture thereof.

Specific examples of the lubricant include stearic acid, metal stearate salt such as calcium stearate or magnesium stearate, talc, colloidal silica, sugar fatty acid ester, hydrogenated vegetable oil, wax with high melting point, glyceryl dibehenate and a mixture thereof.

The average hardness of the chewable tablet in accordance with the present invention may be controlled for rapid disintegration in the oral cavity, preferably in the range of 2 kp to 17 kp. In accordance with one embodiment of the present invention, the average hardness of the chewable tablet may be in the range of 2 to 15 kp, more preferably 8 to 15 kp. If the value is less than 2 kp, the chewable tablet easily shatters, thereby causing a difficulty during packaging and distribution processes. Whereas, the hardness of greater than 17 kp causes a delay in disintegration of chewable tablet in the oral cavity, thereby lowering patient compliance.

Hereinafter, the present invention is described more specifically by the following examples, but these are provided only for illustration purposes, and the present invention is not limited thereto. Reference Example: Measurement of Swelling Coefficient of Disintegrant

10 grams of each of Polyplasdone XL-10 (ISP Pharmaceuticals, U.S.), Polyplasdone XL (ISP Pharmaceuticals, U.S.), Kollidon CL (BASF, Germany), Kollidon CL-M (BASF, Germany), sodium croscarboxymethylcellulose (Ac-Di- Sol, DFE, Germany), and corn starch (StarCap 1500, Roquette, France) were placed in separate 100 mL volumetric flasks, and added with water to the 100 mL mark. The resulting mixtures were stirred for 24 hours and degrees of swelling in each sample were measured (Anisul Q. et al., A comparative study of current superdisintegrants, Pharmaceutical technology 2006). The results of the measurement of the swelling coefficients of the samples are as follows: Polyplasdone XL-10 (5.4 L/kg), Polypladone XL (5.8 L/kg), Kollidon CL (4.3 L/kg), Kollidon CL-M (7.2 L/kg), sodium croscarboxymethylcellulose (Ac-Di- Sol) (13.5 L/kg), and corn starch (StarCap 1500) (1.8 L/kg).

Example 1 and Comparative Examples 1 and 2: Preparation of chewable tablets with different types of disintegrants In accordance with the ingredients listed in Table 1 below, a chewable tablet comprising sildenafil as an active ingredient was prepared by using sildenafil free base (Dong Woo Pharm., Korea), spray dried mannitol (Roquette, France), crospovidone, (diameter of 30 to 50 μηι, Polyplasdone XL-10, ISP Pharmaceuticals, U.S.), enzymatically modified stevia (Daepyung, Korea), peppermint powder (Samjung Flavor, Korea), Blue No. 2 aluminum lake (Bolak, Korea) and magnesium stearate (NOF, Japan). Specifically, the ingredients listed in Table 1 were mixed and tabletized with the compression force of about 5 kN using a tableting machine (MRC-45, Sejong Pharmatech, Korea) to obtain the chewable tablet having a hardness of about 15 kp.

Also, for Comparative Examples 1 and 2, the above procedure was repeated, except for using sodium croscarboxymethylcellulose (diameter of 45 to 74 μπι, DFE, Germany) and corn starch (diameter of 74 to 125 μιη, Roquette, France) to obtain chewable tablets. [Table 1]

Examples 1 to 4: Preparation of chewable tablets with different diameter of crospovidone

In accordance with the ingredients listed in Table 2 below, chewable tablets were prepared by repeating the procedure of Example 1 , except for using commercially available crospovidone with different diameters: Polyplasdone XL (diameter of 100 to 130 μιη, ISP Pharmaceuticals, U.S.), Kollidon CL (diameter of 50 to 250 μπι, BASF, Germany) and Kollidon CL-M (diameter of 5 to 15 μηι).

[Table 2]

Enzymatically

10 1.82 10 1.82 10 1.82 10 1.82 modified stevia

Peppermint

5 0.91 5 0.91 5 0.91 5 0.91 powder

Blue No. 2

0.5 0.09 0.5 0.09 0.5 0.09 0.05 0.09 aluminum lake

Magnesium

5 0.91 5 0.91 5 0.91 5 0.91 stearate

Examples 1, 5 to 7 and Comparative Examples 3, 4: Preparation of chewable tablets with different amounts of crospovidone In accordance with the ingredients listed in Table 3 below, chewable tablets were prepared by repeating the procedure of Example 1, except for changing the amounts of crospovidone used.

[Table 3]

Examples 1, 8 and Comparative Examples 5, 6: Preparation of chewable tablets with different types of excipients

In accordance with the ingredients listed in Table 4 below, chewable tablets were prepared by repeating the procedure of Example 1 , except for using anhydrous lactose (DFE, Germany), microcrystalline cellulose (Mingtai, Taiwan), or anhydrous calcium hydrogen phosphate (Innophos, U.S.) instead of spray dried mannitol.

[Table 4]

Experimental Example: Degree of feeling of irritation in the oral cavity and disintegration test

(1) Degree of feeling of irritation in the oral cavity

The degree of feeling of irritation in the oral cavity was evaluated when chewable tablets obtained in Examples 1 to 8 and Comparative Examples 1 to 6 were administered, and the results are shown in Tables 5, 7, 9 and 11.

The test was performed on 10 healthy human male subjects in their 20s who volunteered. In order to minimize individual differences, an oral administration procedure was set up and applied to the test, which comprises the following steps of: (1) using approximately 20 mL of water to wet the oral cavity so as to prevent dry mouth; (2) administering the tablet in the mouth, followed by chewing the tablet within 20 seconds using teeth near incisor teeth to prevent the tablet pieces to be stuck between teeth; and (3) evaluating a feeling of irritation in the oral cavity by rubbing the tablet particles formed against tongue and palate. The results were evaluated on a scale of 0 to 5 (1 : feeling of irritation disappears within 15 sec, 2: feeling of irritation disappears within 30 sec, 3: feeling of irritation disappears within 45 sec, 4: feeling of irritation disappears within 60 sec, 5: feeling of irritation remains after 60 sec and difficult to swallow).

(2) Disintegration test of chewable tablet

The disintegration test was performed on the chewable tablets comprising sildenafil obtained in Examples 1 to 8 and Comparative Examples 1 to 6 and the results are shown in Tables 6, 8, 10 and 12 below. The test was conducted in accordance with the disintegration test method described in Korea pharmacopoeia using distilled water as a disintegration solution and the disintegration time was recorded when the tablet was completely dissolved on the bottom of the container.

(3) Result and analysis

The results of the degree of feeling of irritation in the oral cavity and disintegration test of the chewable tablets prepared by employing different types of disintegrant obtained in Example 1 and Comparative Examples 1 and 2 are shown in Tables 5 and 6 below.

[Table 5]

[Table 6]

As shown in Table 5 above, the satisfaction levels of patients for the chewable tablet comprising crospovidone of Example 1 were high, having the average degree of feeling of irritation value of 0.9, whereas the average degrees of feeling of irritation for Comparative Examples of 1 and 2 each comprising sodium croscarboxymethylcellulose and corn starch were 4.3 and 2.9, respectively, which are very high showing relatively low levels of patient satisfaction. The degrees of feeling of irritation of crospovidone were low because it has the average diameter of 30 to 50 μπι and does not swell much after coming in contact with water. However, the average diameter of sodium croscarboxymethylcellulose is 45 to 74 μηι and it swells to about 13.5 times its original volume on contact with water; and corn starch has the average diameter of about 74 to 125 urn, but its relatively weak swelling force caused high level of feeling of irritation in the oral cavity. Therefore, it can be concluded that the most preferred disintegrant in the present invention is crospovidone.

Also, as shown in Table 6 above, the disintegration times for the chewable tablets obtained in Example 1 and Comparative Example 1 all came out to be about 10 seconds. Thus, it can be concluded that crospovidone and sodium croscarboxymethylcellulose were suitable as a disintegrant, but corn starch of Comparative Example 2 seemed inappropriate to be used as a disintegrant due to its poor swelling force.

Meanwhile, the results of the degree of feeling of irritation in the oral cavity and disintegration test of the chewable tablets prepared by using different diameters of crospovidone obtained in Examples 1 to 4 and the results are shown in Tables 7 and 8 below. [Table 7]

[Table 8]

As shown in Table 7 above, the satisfaction levels of patients for the chewable tablet comprising crospovidone with different diameters of Examples 1 to 4 were high, having the average degree of feeling of irritation value of 2.2 or less.

Also, as shown in Table 8 above, the disintegration time varied depending on the swelling coefficient. However, the chewable tablets of Examples 1 to 4 all demonstrated short disintegration times.

In summary of the results of Tables 7 and 8, the chewable tablets of the present invention showed high levels of patient satisfaction and short disintegration times when crospovidone having swelling coefficient ranging from 4 to 8 L/kg and having the diameter of 5 to 250 μηι was employed.

Meanwhile, the results of the degree of feeling of irritation in the oral cavity and disintegration time test of the chewable tablets prepared by varying the amount of crospovidone obtained in Examples 1, 5 to 7 and Comparative Examples 3 and 4 and the results are shown in Tables 9 and 10 below.

[Table 9]

[Table 10]

As shown in Table 9 above, the satisfaction levels of patients for the chewable tablets comprising crospovidone in an amount of 5 to 90 mg of Examples 1, 5 to 7 and Comparative Example 3 were high, having the average degree of feeling of irritation value of 3 or less, whereas Comparative Example 4 which employed crospovidone in an amount of 120 mg (18.74% by weight), resulted relatively high degree of feeling of irritation. This is because crospovidone is insoluble in water, and as the amount of crospovidone increases, the amount remains in the oral cavity also increases.

Also, as shown in Table 10 above, the disintegration time was decreased as the amount of crospovidone increased. The disintegration time of Comparative Example 3, wherein the least amount of crospovidone was employed, was 36.3 seconds and the degree of feeling of irritation in the oral cavity was relatively higher than other tablets considering the amount of crospovidone employed, as can be seen in Table 9, owing to the long disintegration time.

In summary of the results of Tables 9 and 10, the amount of crospovidone employed in the chewable tablet of the present invention is preferably 1.5 to 15% by weight, based on the total weight of the formulation.

Meanwhile, the results of the degree of feeling of irritation in the oral cavity and disintegration time test of the chewable tablets prepared by employing different types of excipients obtained in Examples 1, 8 and Comparative Examples 5 and 6, and the results are shown in Tables 1 1 and 12 below.

[Table 11]

[Table 12]

9

As shown in Table 11 above, the satisfaction levels of patients for the chewable tablets comprising spray dried mannitol and anhydrous lactose of Examples 1 and 8 were high, resulting the average degrees of feeling of irritation value of 0.9 to 1.5. Comparative Examples 5 and 6 comprising microcrystalline cellulose and anhydrous calcium hydrogen phosphate resulted relatively higher degrees of feeling of irritation in the oral cavity, 3.3 to 3.6 which was somewhat higher than Examples 1 and 8, yet test subjects did not experience difficulties when they took the tablets. The difference in the average degrees of feeling of irritation was due to water solubility. The spray dried mannitol and anhydrous lactose are highly soluble in water, whereas microcrystalline cellulose and anhydrous calcium hydrogen phosphate are almost insoluble in water. However, the average diameters of microcrystalline cellulose and anhydrous calcium hydrogen phosphate were in the range of 100 to 200 μπι, which were small, and hence the test subjects did not experience unpleasant feelings caused by feeling of irritation.

Also, as shown in Table 12 above, the disintegration time was affected by the solubility of excipients. The chewable tablets of Examples 1 and 8 which employed spray dried mannitol and anhydrous lactose rapidly disintegrated, each having disintegration time of 11.8 and 13.7 seconds, respectively, whereas the chewable tablets of Comparative Examples 5 and 6 which employed microcrystalline cellulose and anhydrous calcium hydrogen phosphate disintegrated relatively slowly, each having disintegration time of 39.5 and 43.5 seconds.

As can be seen from the results of Tables 11 and 12 above, the preferred excipients employable for the chewable tablet in accordance with the present invention are spray dried mannitol and anhydrous lactose; and spray dried mannitol is the most effective in particular. This is due to a porous surface of spray dried mannitol obtained by the spray drying process as well as high solubility of mannitol which disintegrates rapidly in the oral cavity.

Claims

What is claimed is:

1. A chewable tablet comprising a phosphodiesterase-5 (PDE-5) inhibitor or a pharmaceutically acceptable salt thereof; and a disintegrant having a swelling coefficient ranging from 4 to 8 L/kg.

2. The chewable tablet of claim 1, wherein the PDE-5 inhibitor is sildenafil free base.

3. The chewable tablet of claim 1, wherein the chewable tablets further comprises sugar, sugar alcohol or a mixture thereof.

4. The chewable tablet of claim 3, wherein the sugar is selected from the group consisting of lactose, glucose, sucrose, fructose, levulose, maltodextrin and palantinose; and the sugar alcohol is selected from the group consisting of mannitol, sorbitol, xylitol and erythritol.

5. The chewable tablet of claim 3, wherein the sugar alcohol is spray- dried mannitol.

6. The chewable tablet of claim 3, wherein the sugar, sugar alcohol or a mixture thereof is employed in an amount ranging from 10 to 98% by weight, based on the total weight of the formulation.

7. The chewable tablet of claim 1, wherein the diameter of the disintegrant employed is 5 to 250 μιη.

8. The chewable tablet of claim 1, wherein the disintegrant is employed in an amount ranging from 1.5 to 15% by weight, based on the total weight of the formulation.

9. The chewable tablet of claim 1, wherein the average hardness of the tablet is in the range of 2 to 17 kp.

10. The chewable tablet of claim 3, wherein the chewable tablet comprises sildenafil free base, spray-dried mannitol and a disintegrant having a swelling coefficient ranging from 4 to 8 L/kg.

11. The chewable tablet of claim 1, wherein the chewable tablet further comprises one or more of pharmaceutically acceptable additives selected from the group consisting of a flavoring agent, a coloring agent, a sweetening agent and a lubricant.