TW201422224A - Oral composition containing dapoxetine free base - Google Patents

Abstract

The present invention provides a pharmaceutical product that can be orally administered by disintegrating or dissolving in the oral cavity, containing dapoxetine or a pharmaceutically acceptable salt thereof as an active agent, characterized in that the active agent is dapoxetine free base, particularly in the form of films.

Description

Oral composition containing dapoxetine free base

The present invention relates to an oral pharmaceutical product, particularly a pharmaceutical product in the form of a film which provides rapid efficacy, improves taste and can be broken or dissolved in the oral cavity.

Dapoxetine and its pharmaceutically acceptable salts are extremely useful for treating or improving premature ejaculation (see, U.S. Patent No. 7,718,705).

For example, already available in the market Priligy ^TM (Janssen Korea Corporation) is a pharmaceutical product containing Dapoxetine chloride (dapoxetine chloride) as an active ingredient of the lozenges. According to the instructions for use of the tablet, the tablet must be swallowed with at least one full cup of water to avoid bitter taste.

Accordingly, it is an object of the present invention to provide a pharmaceutical product which exhibits the same efficacy as a conventional product and which has a lower bitter taste and can be The medicine is disintegrated or dissolved in the mouth (mouth).

The present invention is intended to develop a product which disintegrates or dissolves in the oral cavity and contains dapoxetine or a pharmaceutically acceptable dapoxetine salt as an active ingredient, compared to conventional products (for example, tablets or capsules). This product can increase the onset time of the drug. However, as indicated by the drug use instructions for commercially available products, it is substantially difficult to develop an orally disintegrating or dissolving product of dapoxetine chloride salt due to the bitter taste of dapoxetine chloride salt.

In order to solve this bitterness problem, the present invention seeks to develop an improved dosage form of dapoxetine from several dapoxetine salts and dapoxetine free base, and surprisingly found that even when collapsed in the oral cavity When administered orally or dissolved, the free base form of dapoxetine exhibits an improved taste and is effective in treating premature ejaculation.

Accordingly, the present invention provides a pharmaceutical product comprising dapoxetine or a pharmaceutically acceptable dapoxetine salt as an active ingredient and which is administered by disintegrating or dissolving in the oral cavity, the pharmaceutical product being characterized by the active ingredient It is dapoxetine free base.

Preferably, the invention is even more particularly useful for obtaining the desired effect by dissolving in the mouth without swallowing.

The pharmaceutical product which can be disintegrated or dissolved in the oral cavity according to the present invention and which is administered orally can be in the form of a film (for example, an oral disintegrating film (ODF)), an oral disintegrating tablet, a chewable tablet, or a granule (preferably No need to use water to take the particles), candy ingots and sugar.

In particular, instead of using dapoxetine salt, instead of dapoxetine free A film product made of a base (for example, ODF) exhibits superior properties and is easy to prepare.

Accordingly, the present invention provides a film product comprising dapoxetine or a pharmaceutically acceptable dapoxetine salt as an active ingredient, and the film product is characterized in that the active ingredient is dapoxetine free base.

In the present invention, the film may be referred to as a sheet, a dissolving film for oral cavity or a disintegrating film for oral cavity, and by placing the film in a mouth, for example, on the tongue or under the tongue and in the oral mucosa, and then the film The film is applied by melting. The film product of the present invention is advantageous for use without the need for water.

The present invention provides a pharmaceutical product comprising dapoxetine free base which can be administered orally by disintegration or dissolution in the oral cavity, the pharmaceutical product providing rapid efficacy and improved taste.

Preferably, the present invention provides a pharmaceutical product comprising dapoxetine free base and which is administered via the oral cavity by disintegrating or dissolving in the oral cavity without swallowing, the pharmaceutical product providing rapid efficacy and improved taste. More preferably, the pharmaceutical product of the invention is in the form of a film.

Various preferred embodiments of the invention are described in detail below in order to provide a better understanding of the invention. However, the present invention may be modified in various ways, and the embodiments should not be construed as limiting the scope of the invention. The embodiments of the present invention are only for better understanding of the present invention by those skilled in the art. use.

<Preparation of ODF products containing dapoxetine>

ODF products containing dapoxetine chloride or dapoxetine free base were prepared according to conventional methods using the ingredients and amounts listed in Table 1.

Specifically, the plasticizer, sweetener, and surfactant are added to distilled water and then stirred until dissolved or dispersed. Dapoxetine free base or dapoxetine chloride salt was added to the above solution and homogenized for 20 minutes at 5000 rpm using a homogenizer (Ultra turrax T-25, IKA). The polymer was added to the resulting solution and stirred again, followed by the addition of perfume to the solution. After the gas in the film forming solution was removed under vacuum, the solution was allowed to cool to room temperature, and then a solution of a suitable thickness was applied to the PE film. Next, drying was carried out at 80 ° C to prepare a film product containing dapoxetine chloride or dapoxetine free base. The prepared film product was cut into several pieces so that each tablet contained 33.6 mg (mg) of dapoxetine chloride salt or 30 mg of dapoxetine free base.

The film product containing dapoxetine free base prepared in Example 1 was excellent in film properties and film processability.

<Preparation of granule products containing dapoxetine>

Granular products containing dapoxetine chloride or dapoxetine free base were prepared according to conventional methods using the ingredients and amounts listed in Table 2.

Specifically, an appropriate amount of polyvinylpyrrolidone is added to distilled water to obtain a binding solution. The binder solution is sprayed into a mixture of the flowing active ingredient and xylitol using a fluid bed granulator to obtain granules. The obtained granules are mixed with sucrose powder to finally prepare a granulated product.

<Preparation of an orally disintegrating ingot containing dapoxetine>

Oral disintegrating tablets containing dapoxetine chloride or dapoxetine free base were prepared according to conventional methods using the ingredients and amounts listed in Table 3.

Specifically, API, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, The low-substituted hydroxypropylcellulose, mannitol, and sucralose are mixed in the above ratio, and magnesium stearate is added to the mixed powder. The resulting mixture was molded into an ingot at a pressure of 8 kilonewtons (kN) to 10 kN to prepare a 200 mg round lozenge.

<Preparation of chewable tablets containing dapoxetine>

Chewable tablets containing dapoxetine chloride or dapoxetine free base were prepared according to conventional methods using the ingredients and amounts listed in Table 4.

Specifically, API, glyceryl monostearate, fully gelatinized starch, microcrystalline cellulose, anhydrous citric acid, mannitol, aspartame and mint The brain powder was mixed in the above ratio, and magnesium stearate was added to the mixed powder. The resulting mixture was molded into an ingot at a pressure of 12 kN to 15 kN to prepare a 500 mg round lozenge.

<bitter test>

The taste of the products prepared in Examples 1 to 4 and Comparative Examples 1 to 4 was evaluated by 10 adult males aged 27 to 53 years. A score of 1 to 5 is used as the evaluation grade, and a score of 5 indicates that the product has an unpleasant taste and is easy to enter. One point indicates that the product has a bitter taste, so it is difficult to enter. That is, the better the taste of the product, the closer its score should be to 5 points, and Table 5 shows the total score of ten males.

As shown in Table 5, when dapoxetine free base was used as an active ingredient, the bitterness unexpectedly decreased.

<Evaluation of early ejaculation improvement>

The assessment of premature ejaculation improvement was performed by 3 adult males aged 31 to 49 who ejaculated within two minutes after insertion into the vagina. Each subject was used to use the film product of Example 1 or Comparative Example 1 about 1.5 hours before sexual activity, and the effects of the product of Example 1 and the product of Comparative Example 1 on improving premature ejaculation were compared (ie, comparative use was carried out). The product of Example 1 and the product of Comparative Example 1 were used to delay the ejaculation duration).

As a result, the product of Example 1 exhibited in three males. The product of Comparative Example 1 was substantially similar to the effect of premature ejaculation improvement.

Claims (4)

A pharmaceutical product comprising dapoxetine or a pharmaceutically acceptable dapoxetine salt as an active ingredient and which is administered by disintegrating or dissolving in the oral cavity, wherein the active ingredient is dapoxetine free base ( Dapoxetine free base). The pharmaceutical product according to claim 1, which does not need to be swallowed but is administered by dissolving in the oral cavity. The pharmaceutical product according to claim 1, which is in the form of a film, an orally disintegrating ingot, a chewable tablet, a granule, a candy ingot or a loquat. The pharmaceutical product of claim 3, which is in the form of a film.