WO2014007775A1 - Nouvelle formulation à dissolution rapide - Google Patents

Nouvelle formulation à dissolution rapide Download PDF

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Publication number
WO2014007775A1
WO2014007775A1 PCT/TR2013/000203 TR2013000203W WO2014007775A1 WO 2014007775 A1 WO2014007775 A1 WO 2014007775A1 TR 2013000203 W TR2013000203 W TR 2013000203W WO 2014007775 A1 WO2014007775 A1 WO 2014007775A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
effervescent
range
agents
formulation according
Prior art date
Application number
PCT/TR2013/000203
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2014007775A1 publication Critical patent/WO2014007775A1/fr

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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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • the present invention is related to pharmaceutical formulations comprising tricyclo[3.3.1.1 3 ' 7 ]decan-l-amine,3,5-dimethyl hydrochloride that shall be used in the treatment of Alzheimer's disease and dementia. Said formulations are characterized in being in effervescent form.
  • Memantine which has the chemical name tricyclo[3.3.1.1 ' ]decan-l amine, 3,5-dimethyl hydrochloride (Formula I), is a non-competitive N-methyl-D-aspartate(NMDA) receptor antagonist neuroprotective agent and it was first disclosed in the application numbered US3391142. In said document, it was indicated that memantine is effective in use for the treatment of Alzheimer's disease and dementia.
  • Memantine is marketed in 10 mg and 20 mg tablet and 5 mg and 10 mg oral drop and oral solution forms.
  • the tablet dosage forms in the present invention are not preferred due to swallowing problems and low bioavailability.
  • Solid dosage forms of this drug (for example tablet) used in the treatment of Alzheimer's disease particularly in patients over 50 years of age are disadvantageous for geriatric patients and people with swallowing difficulties.
  • dosage forms such as oral drop and oral solution on the market complicate the adaptation of the patients to the treatment due to the reasons such as their possibility of uncontrolled dose intake, high production costs, bad taste and the problems they pose during use and carrying.
  • suspension forms have higher bioavailability than solid dosage forms, they are more inconvenient compared to solid dosage forms when evaluated in terms of stability and shelf life.
  • another dosage form provided as an alternative to these dosage forms is fast- dissolving orodispersible dosage forms.
  • the patent application WO2009 004440 discloses dosage forms which comprise memantine and dissolve in mouth in less than 60 seconds.
  • this dosage form disclosed in the application is not an applicable alternative for an active agent known for its bitter taste like memantine.
  • Orodispersible dosage form is not preferred most of the time due to the metallic taste remains in the mouth following the intake of this dosage form.
  • the present invention is related to pharmaceutical formulations comprising memantine that shall be used in the treatment of Alzheimer's disease and dementia and are characterized in being in effervescent form.
  • formulations of the present invention are in the form of effervescent powder, tablet and granule having the advantages of both tablet and suspension forms; and they eliminate the problems, faced with these dosage forms.
  • Effervescent dosage forms are advantageous particularly for patients with dysphagia.
  • the pharmaceutical formulations of the present invention comprise effervescent oral dosage forms comprising memantine and at least one pharmaceutically acceptable excipient in addition to the effervescent couple or comprising only memantine and the effervescent couple.
  • the present invention is related to effervescent oral dosage forms comprising memantine as the active agent, effervescent couple and at least one pharmaceutically acceptable excipient.
  • Memantine in the formulations of the present invention can be in the form of its pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers or combinations thereof in terms of chemical structure; in amorphous or crystalline form or a combination thereof in terms of polymorphic structure.
  • Memantine in the formulations of the present invention is preferably in memantine hydrochloride form.
  • a characteristic of the effervescent formulations of the present invention is that the amount of memantine in the formulation is in the range of 0.1% and 90%, preferably in the range of 0.1% and 85%, more preferably in the range of 0.1% and 80% by weight.
  • the effervescent formulations of the present invention comprise memantine in the range of 1 and 50 mg, preferably in the range of 1 and 45 mg, more preferably in the range of 1 and 40 mg per dosage form.
  • effervescent dosage forms of the present invention Another characteristic of the effervescent dosage forms of the present invention is that said formulations are in effervescent powder, tablet and granule form.
  • a characteristic feature of the effervescent formulations of the present invention is that said formulations are in effervescent powder, tablet or granule form
  • the amount of memantine that said formulations comprise is in the range of 0.1% and
  • the inventors have discovered that the highest solubility is obtained when the average particle size of memantine is -smaller than - -50-- ⁇ in the effervescent formulations comprising memantine.
  • formulations comprise memantine having an average particle size in the range of 1 ⁇ and 45 ⁇ as the active agent.
  • the amount of memantine that said formulations comprise is in the range of 0.1% and 90%, preferably in the range of 0.1% and 85%, more preferably in the range of 0.1% and 80% by weight.
  • the average particle size of memantine comprised in said formulations is smaller than 50 ⁇ , preferably in the range of 1 ⁇ and 50 ⁇ , more preferably in the range of 1 ⁇ and 45 ⁇ .
  • the phrase "average particle size" used hereby refers to volumetric average particle diameter and is shown as d 50 in short.
  • d 5 o means that volumetric half of a substance has a particle size above the value indicated by d 50 and the other half has a particle size below the value indicated by d 0 .
  • D 5 o value can be measured with one of the common devices, e.g. a device measuring particle distribution via laser diffraction (e.g. Malvern Mastersizer etc.).
  • a device measuring particle distribution via laser diffraction e.g. Malvern Mastersizer etc.
  • effervescent formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to memantine and the effervescent couple.
  • excipients that can be comprised in the effervescent formulations of the invention can be selected from a group comprising binders, disintegrants, viscosity enhancing agents, filling agents, drying agents, surfactants, stabilizing agents, oiling agents, lubricants, ' diluents, glidants, wetting agents, oiling agents, pH regulating agents, an effervescent couple comprising at least one pharmaceutically acceptable effervescent acid and at least one effervescent base, gel forming agents, flavoring agents, sweeteners, taste regulating agents. emulsifying agents, antifoaming agents, antioxidants, protective agents, solvents or solvent mixtures, coloring agents and complexing agents or combinations thereof.
  • excipients that can be used in the effervescent formulations of the present invention comprising memantine are selected from a group comprising binders, disintegrants, filling agents, surfactants, stabilizing agents, oiling agents, lubricants, diluents, glidants, an effervescent couple comprising at least one pharmaceutically acceptable effervescent acid and at least one effervescent base, flavoring agents, sweeteners, solvents or solvent mixtures or combinations thereof.
  • the disintegrant that can be used in the effervescent formulations of the invention comprising memantine can be selected from a group comprising carboxyme hyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate.
  • the binder that can be used in the effervescent formulations of the invention comprising memantine can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, maltodextrin, methyl cellulose, povidone, starch.
  • the ratio of at least one pharmaceutically acceptable effervescent acid and the effervescent base used in the effervescent formulations of the present invention comprising memantine is in the range of 0.1 and 10 by weight.
  • the surfactant that can be used in the effervescent formulations :of the invention comprising memantine can be selected from sodium lauryl sulphate, polysorbate, polyoxyethylene, polyoxypropylene glycol and similar agents.
  • the stabilizing agents that can be used in the effervescent formulations of the invention comprising memantine can be selected from a group comprising tocopherol, tetrasodium edetate, nicotinamide, cyclodextrin.
  • the drinkable taste which would provide adaptation of the patients in the effervescent formulations comprising memantine -as the active agent has been provided by use of at least one pharmaceutically acceptable sweetener and at least one flavoring agent and adjusting the ratio of the sweetener and the flavoring agent to each other in the range of 3: 1 and 1 :3, preferably in the range of 2.5.T and 1 :2.5, more preferably in the range of 2:1 and 1 :2.
  • the effervescent formulations of the present invention comprising memantine can optionally comprise one or more active agents in addition to memantine.
  • active agents can be selected from antacid, anticholinergic, antispasmodic, antiemetic, antidiabetic, antipropulsive, antiallergic, antidiarrheal, antiobesity, antithrombotic, antifibrinolytic, antianemic, antihypertensive, antifungal, antipruritic, antipsoriatic, antibiotic, antiseptic, antiacne, antibacterial, antimycotic, antiviral, anti dementia (for instance ginkgo), antineoplastic, antiarrhythmic, antiadrenergic, psychoanaleptic (for instance idebenone), antiepileptic, anti-parkinson, antiprotozoal, anthelmintic, anti-inflammatory, diuretic, laxative, sulphonamide, imidazole, corticosteroid, thiazolidine
  • the pharmaceutical formulations of the present invention comprising memantine and a second active agent in addition can be prepared in any of the dosage forms such as effervescent tablet, effervescent granule, effervescent dry powder; in the case that the two active agents are in different formulations but in the same dosage form, said formulations can be prepared in such forms as layered tablet, capsule; when the two active agents are in different formulations and in different dosage forms, the formulations can be prepared in the form of a treatment package where ceftibuten can be in any of the dosage forms such as effervescent tablet, effervescent granule, effervescent dry powder, and the second active agent can be in any of the solid dosage forms such as tablet, effervescent tablet, effervescent granule, effervescent dry powder, film-coated tablet, enteric coated tablet, dry powder, granule, capsule, extended- release tablet, modified-release tablet, delayed-
  • any production method present in the prior art can be used for formulating the formulations of the invention; wet granulation, dry granulation and dry blending methods are among these production methods.
  • the effervescent formulations of the invention- can be produced in accordance with any of the production methods given below; 1. Mixing the active agent memantine and the second active agent, if present, homogeneously with at least one pharmaceutically acceptable excipient and, if necessary, adding at least one of the excipients stated above; treating the mixture- optionally with at least one pharmaceutically acceptable lubricant; giving a desired shape to the obtained mixture,
  • the effervescent formulations of the invention are preferably " in the form of tablet. "
  • the pharmaceutical formulations of the present invention are used in the prophylaxis and the treatment of Alzheimer's disease and dementia.
  • Example I Effervescent formulations comprising memantine
  • the effervescent formulation given above is produced according to. any of the methods in the . prior art and explained in the description part in -detail and presented after preparing it in a desired dosage form.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des formulations pharmaceutiques comprenant de l'hydrochlorure de tricyclo[3.3.1.13,7]décan-1-amine,3,5-diméthyle devant être utilisées dans le traitement de la démence et de la maladie d'Alzheimer. Ces formulations se caractérisent en ce qu'elles se présentent sous une forme effervescente.
PCT/TR2013/000203 2012-07-02 2013-07-02 Nouvelle formulation à dissolution rapide WO2014007775A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201207631 2012-07-02
TR2012/07631 2012-07-02

Publications (1)

Publication Number Publication Date
WO2014007775A1 true WO2014007775A1 (fr) 2014-01-09

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ID=49170842

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2013/000203 WO2014007775A1 (fr) 2012-07-02 2013-07-02 Nouvelle formulation à dissolution rapide

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WO (1) WO2014007775A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9750705B2 (en) 2012-08-31 2017-09-05 The Regents Of The University Of California Agents useful for treating obesity, diabetes and related disorders
US10420718B2 (en) 2014-07-02 2019-09-24 University Of Bradford Effervescent compositions containing co-crystals of the acid part

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3391142A (en) 1966-02-09 1968-07-02 Lilly Co Eli Adamantyl secondary amines
CN1742711A (zh) * 2005-09-23 2006-03-08 北京阜康仁生物制药科技有限公司 盐酸美金刚泡腾片及其制备方法
WO2007113856A2 (fr) * 2006-03-31 2007-10-11 Rubicon Research Private Limited Comprimés se désagrégeant dans la cavité orale
WO2009004440A2 (fr) 2007-06-29 2009-01-08 Orchid Chemicals & Pharmaceuticals Limited Compositions à dissolution rapide de chlorhydrate de mémantine
WO2012026902A1 (fr) * 2010-08-25 2012-03-01 Mahmut Bilgic Combinaisons comprenant du donépézil, de la mémantine et de l'extrait de gingko biloba

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3391142A (en) 1966-02-09 1968-07-02 Lilly Co Eli Adamantyl secondary amines
CN1742711A (zh) * 2005-09-23 2006-03-08 北京阜康仁生物制药科技有限公司 盐酸美金刚泡腾片及其制备方法
WO2007113856A2 (fr) * 2006-03-31 2007-10-11 Rubicon Research Private Limited Comprimés se désagrégeant dans la cavité orale
WO2009004440A2 (fr) 2007-06-29 2009-01-08 Orchid Chemicals & Pharmaceuticals Limited Compositions à dissolution rapide de chlorhydrate de mémantine
WO2012026902A1 (fr) * 2010-08-25 2012-03-01 Mahmut Bilgic Combinaisons comprenant du donépézil, de la mémantine et de l'extrait de gingko biloba

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9750705B2 (en) 2012-08-31 2017-09-05 The Regents Of The University Of California Agents useful for treating obesity, diabetes and related disorders
US10420718B2 (en) 2014-07-02 2019-09-24 University Of Bradford Effervescent compositions containing co-crystals of the acid part

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