Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/13—Amines
  • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
  • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
  • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
  • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
  • A61K9/1605—Excipients; Inactive ingredients
  • A61K9/1629—Organic macromolecular compounds
  • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P15/00—Drugs for genital or sexual disorders; Contraceptives

Definitions

• the present invention relates to oral pharmaceutical preparations, in particular film-like preparations, taken by dissolution or disintegration in the oral cavity, in which the manifestation of the effect is rapid and the taste is improved.
• Dapoxetine and its pharmaceutically acceptable salts are very useful for the treatment or amelioration of premature ejaculation (see US Pat. No. 7,718,705).
• Fringe Tablet TM (Jansen Korea Co., Ltd.), which contains dapoxetine hydrochloride as an active ingredient, is currently on the market and should be swallowed at a time to avoid bitterness in the “Usage / Dose” section of the manual and with at least 1 cup of water. It is stated to take.
• the technical problem to be achieved by the present invention is to provide a pharmaceutical preparation that can be taken by dissolving or disintegrating in the mouth (oral cavity) while reducing the bitter taste while showing the same effect.
• the present invention provides a pharmaceutical formulation with improved taste that is dissolved or disintegrated in the mouth, characterized in that it comprises a dapoxetine free base as an active ingredient.
• the present inventors dissolve or disintegrate in the mouth instead of conventional tablets, capsules, and the like to promote the onset time of the preparation of the formulation containing dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient.
• the present inventors have experimented with various kinds of other salts and free bases, and as a result, the taste of the dapoxetine free base is dramatically improved, and even when dissolved or disintegrated in the mouth, the treatment effect of premature ejaculation is used. It was an amazing invention that there was no influence.
• the present invention is a pharmaceutical preparation comprising dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient and dissolved or disintegrated in the mouth, wherein the active ingredient is dapoxetine free base.
• dapoxetine or a pharmaceutically acceptable salt thereof as an active ingredient and dissolved or disintegrated in the mouth, wherein the active ingredient is dapoxetine free base.
• the effect of the present invention is more pronounced in the formulations which are taken by dissolution in the mouth without swallowing.
• pharmaceutical preparations which are taken by dissolving or disintegrating in the mouth include, for example, film formulations such as ODF; Oral disintegrating tablets; Chewable tablets; Granule formulations (preferably granule formulations which can be taken without water); Formulations in the form of candies; Caramel forms, and the like.
• the present invention provides a formulation of a film formulation, wherein in the film formulation comprising dapoxetine or a pharmaceutically acceptable salt thereof as the active ingredient, the active ingredient is dapoxetine free base.
• the film may be referred to as a strip, an orally dissolving film, an orally disintegrating film, or the like, and is dissolved in the oral cavity of the tongue, oral mucosa, and sublingual.
• Film formulations according to the invention have the advantage that they can be taken without water.
• the present invention provides a pharmaceutical formulation containing dapoxetine free base, which is taken by dissolution or disintegration in the mouth, characterized by rapid effect expression and improved taste. More preferably, the present invention provides a pharmaceutical preparation containing dapoxetine free base which is taken by dissolution or disintegration in the mouth without swallowing, characterized in that the effect expression is rapid and the taste is improved. Even more preferably the pharmaceutical formulation is a film formulation.
• ODF formulation film formulation containing dapoxetine hydrochloride or dapoxetine free base was prepared in a conventional manner according to the formulation of Table 1 below.
• a plasticizer, a sweetening agent, and a surfactant are added to the purified water, followed by stirring to dissolve or disperse the same, followed by addition of dapoxetine free base or dapoxetine hydrochloride to the ultra turrax.
• T-25, IKA was homogenized at 5,000 rpm for 20 minutes.
• a polymer was added to this was added a polymer and stirred again, after which a flavor was added.
• the gas in the film preparation solution was removed under vacuum conditions, cooled to room temperature, and then applied to have a suitable thickness on the PE film. After drying at 80 °C to prepare a film formulation comprising a dapoxetine hydrochloride or dapoxetine free base.
• the film was then cut to contain 33.6 mg of dapoxetine hydrochloride or 30 mg of dapoxetine free base.
• Example 1 using dapoxetine free base was superior.
• Formulations of granule formulations containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 2 below.
• the binder solution was prepared by dissolving polyvinylpyrrolidone in an appropriate amount of purified water. Thereafter, granules were prepared by spraying the binder solution on a mixture of the active ingredient and xylitol in the flow using a fluid bed granulator. Sucrose powder and fragrance were mixed with the prepared granules to prepare a final granule formulation.
• Oral disintegrating tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 3 below.
• API microcrystalline cellulose
• anhydrous calcium hydrogen phosphate low-substituted hydroxypropyl cellulose
• mannitol mannitol
• sucralose magnesium stearate was added to the mixed powder and further mixed.
• Tablets were prepared by tableting the obtained mixture with a tableting machine (tableting conditions: tableting pressure 8-10 kN, 200 mg / tablet, round shape).
• Chewable tablets containing dapoxetine hydrochloride or dapoxetine free base were prepared in a conventional manner according to the formulation of Table 4 below.
• API, glyceryl monostearate, pregelatinized starch, microcrystalline cellulose, citric anhydride, mannitol, aspartame, menthol powder are mixed in the above ratio, and then magnesium stearate is added to the mixed powder and further mixed. It was. Tablets were prepared by tableting the obtained mixture with a tableting machine (pressing conditions: tableting pressure 12-15 kN, 500 mg / tablet, prototype).
• Example 1-4 and Comparative Example 1-4 prepared above were performed using 10 adult males aged 27 to 53 years. A five-point scale was used for the evaluation, and when the dose was very good because there was no problem with the taste, five points were used. That is, the better the taste was to give a score close to 5 points, the sum of the scores of 10 people is shown in Table 5.
• Example 1 Three men aged 31-39 who had less than 2 minutes to ejaculate after vaginal insertion were compared and evaluated.
• the film formulation of Example 1 or Comparative Example 1 was administered about 1.5 hours before sexual activity, and the premature ejaculation improvement effect of Example 1 was relatively compared to the premature ejaculation improvement effect of Comparative Example 1 (that is, the assessment of Comparative Example 1 Comparing the increase in delay time with the increase in ejaculation delay time of Example 1).
• Example 1 As a result of the experiment, in all three patients, the effect of improving premature ejaculation of Example 1 and Comparative Example 1 was almost similar.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical & Material Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Nutrition Science (AREA)
• Physiology (AREA)
• Endocrinology (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Reproductive Health (AREA)
• Zoology (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

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Citations (5)

• 2013
  • 2013-09-11 WO PCT/KR2013/008200 patent/WO2014042416A1/fr not_active Ceased
  • 2013-09-13 TW TW102133202A patent/TW201422224A/zh unknown
  • 2013-09-13 AR ARP130103296A patent/AR092570A1/es unknown

Patent Citations (5)

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