EP3618812A1 - Comprimé orodispersible, contenant un anti-histaminique h1 - Google Patents

Comprimé orodispersible, contenant un anti-histaminique h1

Info

Publication number
EP3618812A1
EP3618812A1 EP18721783.1A EP18721783A EP3618812A1 EP 3618812 A1 EP3618812 A1 EP 3618812A1 EP 18721783 A EP18721783 A EP 18721783A EP 3618812 A1 EP3618812 A1 EP 3618812A1
Authority
EP
European Patent Office
Prior art keywords
orodispersible tablet
orodispersible
range
tablet according
tablet
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP18721783.1A
Other languages
German (de)
English (en)
Inventor
Sarah-Lena GREBE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Stada Arzneimittel AG
Original Assignee
Stada Arzneimittel AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Stada Arzneimittel AG filed Critical Stada Arzneimittel AG
Publication of EP3618812A1 publication Critical patent/EP3618812A1/fr
Pending legal-status Critical Current

Links

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
    • A61K9/0012—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates

Definitions

  • the present invention relates to an orodispersible tablet, in particular for the treatment of insomnia, comprising as active pharmaceutical ingredient a hi antihistaminic agent selected from the group consisting of doxylamine and its
  • Blockade of ⁇ receptors inhibit the effect of histamine and thus have an anti-allergic effect.
  • Doxylamine and diphenhydramine are among the first generation antihistamines of Hi and are well absorbed into the central nervous system. Due to the blockade of central Hi receptors, these antihistamines additionally have a sedating and antihistamines
  • Doxylamine-containing drugs are e.g. for the immobilization of nex'vos patients, for the treatment of restlessness and
  • Vitarain B6 Further Applications in combination with Vitarain B6 are the treatment of nausea and vomiting and in combination with paracetamol, dextromethorphan and optionally ephedrine the symptomatic treatment of colds.
  • Diphenhydramine is also used to treat single and
  • diphenhydramine has FDA approval
  • a doxylamine supplement for the treatment of sleep disorders is marketed under the name Hoggar 'Night. These are tablets that are swallowed whole with swallowed liquid.
  • a diphenhydramine preparation for the treatment of sleep disorders is marketed under the trade name Hemodorm. These are also tablets, which are swallowed whole with liquid by swallowing.
  • the object is to provide a dosage form containing a Hi-Antihistaminika selected from the group consisting of doxylamine and diphenhydramine, which can be relatively easily taken and thus has a higher patient acceptance.
  • Orodispersible tablet in particular for the treatment of
  • Insomnia comprising as active pharmaceutical ingredient a hi antihistamines selected from the group consisting of Diphenhydramine and its pharmaceutically acceptable salts.
  • the orodispersible tablets according to the invention are tablets which dissolve relatively quickly in the mouth. They have the advantage that they can also be taken without problems by persons with dysphagia and when lying down and that the active substance may also be resorbed via the oral mucosa, which is why the pharmaceutical effect can occur comparatively quickly in the melting tablets according to the invention.
  • the active substance may also be resorbed via the oral mucosa, which is why the pharmaceutical effect can occur comparatively quickly in the melting tablets according to the invention.
  • the pharmaceutical effect can occur comparatively quickly in the melting tablets according to the invention.
  • the fused tablet according to the invention comprises as active ingredient a Hi antihistamine selected from the group consisting of doxylamine and its pharmaceutically acceptable salts and diphenhydramine and the pharmaceutic thereof
  • the active ingredient in the enamel tablet is in non - ion exchanger bound form, preferably in free form cost-effective provision of the orodispersible tablet according to the invention allows.
  • the fact that the active ingredient in the orodispersible tablet according to the invention is preferably in free unbound form means in particular that the active ingredient is present as such in the orodine tablet and not in chemically bound form such as complex (coordinatively) bound form,
  • Ion exchange material such as a. Ion exchange resin.
  • the fused tablet has a fracture strength F in a range of 30 N to 120 N, preferably a fracture strength F in a range of 40 N to 110 N, more preferably one
  • Breaking strength F in a range of 50 N to 100 K more preferably a breaking strength F in a range of 60 N to 100 N and more preferably a breaking strength F in a range of 70 N or SO N to 100 N.
  • the breaking strength F is to be determined in accordance with the European Pharmacopoeia, 8th Edition, Grundwerk 2014, Volume 1, page 412, Item 2.9.8 "Breaking strength of tablets" a tablet hardness tester by uniaxial vertical
  • Load between two horizontal jaws with plane-parallel surfaces is measured by taking a controlled force-displacement curve, during which the sample is placed on the lower jaw and the progressively lowered upper jaw.
  • the breaking strength F is determined by means of a tablet hardness tester with the designation Dr. med. Schleuniger Pharmatron Model 6 D is determined.
  • Round tablets i. Tablets having a circular cross-section such as e.g. round flat biplane, biconvex or biconcave tablets, are used in the
  • the fracture strength F of the orodispersible tablet according to the invention can - as known to those skilled in the art, for example, on the type and amount of the pharmaceutical
  • Adjuvants such as the binder used and on the size of the applied pressing force can be adjusted in the tableting.
  • the fracture strength F of a fused tablet may depend on its shape and dimensions. It can therefore
  • the mechanical strength of the orodispersible tablet according to the invention is the geometry of the
  • the compressive strength ⁇ is determined by means of the experimentally determined fracture strength F
  • the compressive strength ⁇ will be determined by the following
  • D is the tablet diameter
  • Compressive strength ⁇ calculated by the following mathematical relationship ⁇ see "The Tablet", A. Ritschel et a 2nd edition, Editio-Cantor-Verlag, 2002, ISBN 3-87193-228-0)
  • the Schrveiztabiette a compressive strength ⁇ greater than or equal to 0.4 30 N / mm 2 exhibit ", preferably a compressive strength o in one
  • the orodispersible tablet has a disintegration time in a range of 20 s or 60 s to 180 s, preferably a disintegration time in a range of 70 s to 150 s and more preferably a disintegration time in a range of 80 s to 120 s,
  • the orodispersible tablet has a friability of less than / equal to 1%, preferably a friability of less than / equal to 0.5% and most preferably a friability of 0.1% to 0 , 4%.
  • the friability is to be determined according to Ph.Eur, 8th Edition, Grundwerk 2014, Volume 1, page 411 ff., Item 2.9.7 "Friability of Uncoated Tablets".
  • orodispersible tablet it is provided that the fusible tablet is directly tabletted. This will provide a relatively low cost of the
  • the orodispersible tablet is free of an ion exchange material, in particular free of an ion exchange resin.
  • Active ingredient in the composition according to the invention is the Use of a relatively expensive ion exchange material to which the active ingredient is complexed, not necessary.
  • the enamel tablet is free of pyridoxine and free of a salt of pyridoxine.
  • Orodispersible tablet is. This will disable the use of
  • the active ingredient is doxylamine succinate, in particular
  • Doxy1aminesuccinate - hemihydrate exhibits a relatively high chemical stability in the hot-melt tab according to the invention, which is why the hot-melt tab is characterized by a relatively long shelf life.
  • Diphenhydramine hydrochloride has a relatively high chemical stability in the orodispersible tablet according to the invention, which is why the melting point is characterized by a relatively long shelf life.
  • Schmelztabiette invention is provided that the active ingredient in the Schmelztabiette in crystalline form.
  • the active ingredient in the According to the invention orodispersible tablet has a relatively high chemical stability, which is why the orodispersible tablet is characterized by a relatively long shelf life. According to a further preferred embodiment of the form
  • the tablet is intended » that the active ingredient in the orodispersible tablet in an amount in one
  • the tablet according to the invention is intended » that the enamel tablet comprises a taste masking agent.
  • the taste-masking agent comprises at least one cyclodextrin
  • Orodispersible tablet In this context it is
  • the taste masking agent is a combination of ⁇ - cyclodextrin, sucralose and a
  • ⁇ romastoff comprises, more preferably a combination of ⁇ -cyciodextrin, sucralose, strawberry flavor, and rhababer-vanilla flavor.
  • Orodispersible a water-soluble and a
  • Fillers serve the purpose of increasing the volume of tablets to a suitable size, especially for low-dose tablets.
  • the amount of filler depends on its nature, the size of the tablet and the amount of the active ingredient.
  • water-soluble is a water solubility at a temperature of 15 ° C to 25 ° C of more than 33 mg per ml understood, preferably a water solubility of 100 mg per ml to 1000 mg per ml.
  • Under water insoluble becomes a water solubility at a temperature of 15 ° C. up to 25 ° C of less than 1 rag per ml understood, preferably a water solubility of less than 0, 1 mg per ml.
  • the water-soluble filler is selected from the group
  • the sugar or the sugar alcohol is selected from the group consisting of dextrose, lactose, mannitol, sorbitol,
  • the water-soluble filler is mannitol. According to a further preferred embodiment of the orodispersible tablet according to the invention, it is provided that the water-insoluble filler is selected from the group consisting of aluminum hydroxide, barium sulfate,
  • the water-insoluble filler is starch.
  • Binder comprises, preferably microcrystalline cellulose.
  • the orodispersible tablet comprises one or more pharmaceutical excipients selected from the group consisting of a
  • a typical orodispersible tablet provided by the present invention is a orodispersible tablet for the treatment of sleep disorders, comprising as the sole pharmaceutical agent
  • At least one Cycl.ode.xtrin at least one sweetening agent and at least one flavoring agent, preferably one
  • Taste masking agent comprising ⁇ -cyclodextrin
  • Sucralose and a flavoring agent more preferably one
  • Taste masking agent comprising ⁇ -cyclodextrin
  • Sucralose, strawberry flavor, and rhababer-vanilla flavor wherein the ore tablet has a fracture toughness F in a range of 50 N to 100 N.
  • An orodispersible tablet is an orodispersible tablet for the treatment of insomnia, comprising only one
  • Diphenhydramine hydrochloride preferably in non-ion exchange bonded form, preferably in free
  • At least one cyclodextrin at least one sweetener and at least one flavoring agent, preferably one
  • Taste masking agent comprising ⁇ -cyclodextrin
  • Sucralose and a flavoring agent more preferably one
  • Taste masking agent comprising ⁇ -cyclodextrin
  • Sucralose, strawberry flavor, and rhababer-vanilla flavor wherein the orodispersible tablet has a fracture toughness F in a range of 50 N to 100 N.
  • the present invention further relates to a
  • Orodispersible tablets according to the invention for use in the treatment of sleep disorders.
  • the present invention also relates to a
  • Orodispersible tablet comprising the steps: - Provision of the active substance;
  • the active ingredient doxylamine succinate and the taste masking agent ⁇ -cyclodextrin were each sieved and then mixed with each other to obtain a drug mixture.
  • the filler in the form of mannitol / corn starch composition (Peariitoi 1 Flash), the flow control agent silicon dioxide, the binder microcrystalline cellulose, the disintegrant crospovidone and the taste masking agents sucralose, strawberry flavor and rhababer-vanilla flavor j each sieved and then also mixed together to obtain an auxiliary material mixture.
  • the breaking strength F of the tablets according to Ph.Eur. 2.9.8 was determined by means of a tablet hardness tester with the name Dr. Measure Schleuniger Pharmatron Model 6 D. The orientation of the tablets at measurement was such that they were broken across the ridge (i.e., radially).
  • the decay time according to Ph.Eur. 2.9.1 was determined by means of the medium of water.
  • Example 2 Orodispersible tablets containing 50 mg as active ingredient were obtained
  • Diphenhydramine hydrochloride prepared.
  • the orodispersible tablets have the composition given in Table 2;
  • Orodispersible tablets containing 25 mg of doxylamine succinate were prepared as the active ingredient.
  • the orodispersible tablets have the composition given in Table 3: Table 3:
  • Embodiment 1 produced -. To obtain round
  • biplane orodispersible tablets with a diameter of 12.7 mm and a thickness of 4.5 mm - and measured analogously to Example 1.
  • Embodiment 1 prepared - to obtain round biplane orodispersible tablets with a diameter of 12.7 mm and a thickness of 4.5 mm - and measured analogously to the embodiment.
  • Embodiment 5 is a diagrammatic representation of Embodiment 5:
  • the painkillers have the composition given in Table 5:
  • Embodiment 1 prepared - to obtain round biplane orodispersible tablets with a diameter of 12.7 mm and a thickness of 4.5 mm - and measured analogously to Example 1.
  • Diphenhydraminhydrochoride prepared.
  • the orodispersible tablets have the. Composition given in Table 6:
  • Embodiment 1 prepared - to obtain round biplane orodispersible tablets with a diameter of 12.7 mm and a thickness of 4.5 mm - and analog out of game play 1 game measured.
  • Embodiment 7 is a diagrammatic representation of Embodiment 7:
  • the orodispersible tablets have the composition given in Table 7.
  • Orodispersible tablets containing 25 mg of doxylamine succinate were prepared as the active ingredient.
  • the orodispersible tablets have the composition given in Table S:
  • Embodiment 1 produced - measured to obtain round biplanar 5 orodispersible tablets with a diameter of 12.7 mm and a thickness of 4, 5 mm ⁇ ⁇ ⁇ ⁇ and analog Embodiment 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne un comprimé orodispersible, en particulier pour le traitement de troubles du sommeil, comprenant comme substance active pharmaceutique un anti-histaminique H1 choisi dans le groupe constitué de la doxylamine et ses sels pharmaceutiquement acceptables et de la diphénhydramine et ses sels pharmaceutiquement acceptables. La présente invention concerne en outre le comprimé orodispersible selon l'invention pour une utilisation destinée au traitement de troubles du sommeil et un procédé de fabrication du comprimé orodispersible selon l'invention.
EP18721783.1A 2017-05-02 2018-05-02 Comprimé orodispersible, contenant un anti-histaminique h1 Pending EP3618812A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP17000750.4A EP3398590A1 (fr) 2017-05-02 2017-05-02 Comprimé orodispersible contenant un antihistaminique h1
PCT/EP2018/061187 WO2018202700A1 (fr) 2017-05-02 2018-05-02 Comprimé orodispersible, contenant un anti-histaminique h1

Publications (1)

Publication Number Publication Date
EP3618812A1 true EP3618812A1 (fr) 2020-03-11

Family

ID=58669554

Family Applications (2)

Application Number Title Priority Date Filing Date
EP17000750.4A Withdrawn EP3398590A1 (fr) 2017-05-02 2017-05-02 Comprimé orodispersible contenant un antihistaminique h1
EP18721783.1A Pending EP3618812A1 (fr) 2017-05-02 2018-05-02 Comprimé orodispersible, contenant un anti-histaminique h1

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP17000750.4A Withdrawn EP3398590A1 (fr) 2017-05-02 2017-05-02 Comprimé orodispersible contenant un antihistaminique h1

Country Status (2)

Country Link
EP (2) EP3398590A1 (fr)
WO (1) WO2018202700A1 (fr)

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6872405B2 (en) * 2001-05-10 2005-03-29 Yamanouchi Pharmaceutical Co., Ltd. Quick-disintegrating tablet in buccal cavity and manufacturing method thereof
US20060115529A1 (en) * 2003-05-07 2006-06-01 Seonghoon Jeong Fast-melting tablets having taste-masking and sustained release properties
US9884014B2 (en) * 2004-10-12 2018-02-06 Adare Pharmaceuticals, Inc. Taste-masked pharmaceutical compositions
US8858210B2 (en) * 2009-09-24 2014-10-14 Mcneil-Ppc, Inc. Manufacture of variable density dosage forms utilizing radiofrequency energy
EP2500016A1 (fr) * 2011-03-18 2012-09-19 Laboratorios Del. Dr. Esteve, S.A. Complexe de résinate de doxylamine
CN102488681B (zh) * 2011-12-21 2013-03-13 西南大学 布洛芬苯海拉明口腔崩解片及其制备方法
US9855227B2 (en) * 2015-12-18 2018-01-02 The Procter & Gamble Company Quick dissolving diphenhydramine oral dosage form

Also Published As

Publication number Publication date
EP3398590A1 (fr) 2018-11-07
WO2018202700A1 (fr) 2018-11-08

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