WO2013100876A1 - Formulations de rispéridone - Google Patents

Formulations de rispéridone Download PDF

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Publication number
WO2013100876A1
WO2013100876A1 PCT/TR2012/000231 TR2012000231W WO2013100876A1 WO 2013100876 A1 WO2013100876 A1 WO 2013100876A1 TR 2012000231 W TR2012000231 W TR 2012000231W WO 2013100876 A1 WO2013100876 A1 WO 2013100876A1
Authority
WO
WIPO (PCT)
Prior art keywords
risperidone
range
formulation
weight
pharmaceutical formulation
Prior art date
Application number
PCT/TR2012/000231
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 WO2013100876A1 publication Critical patent/WO2013100876A1/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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • 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
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to pharmaceutical formulations comprising risperidone that shall be used in the treatment of schizophrenia, affective symptoms related to schizophrenia, manic episodes of bipolar disorder and restlessness related to autistic disorder.
  • Risperidone was first disclosed in the application numbered EP 196132. In said document, it has been disclosed that risperidone is effective when used in the treatment of psychotic disorders.
  • Risperidone is available in the forms of 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg effervescent tablet, film coated tablet, orodispersible tablet, 1 mg/ml oral solution and 25 mg, 37.5 mg, 50 mg vials for injection on the market.
  • the formulations comprising risperidone are formulated in solid oral dosage forms such as tablet, some problems are encountered regarding dissolution in the body, disintegration rate and homogeneity of the tablets obtained.
  • the formulations comprising risperidone are prepared in film coated tablet form, it is seen that the tablets obtained do not dissolve effectively in gastrointestinal liquid and dispersion of the tablets in the liquid is slow after they are taken into the body. This leads to reduction in absorption of the active agent risperidone comprised in the drug into the blood circulation. Said reduction in absorption of the drug brings with the problems such as decrease in bioavailability of the drug and difficulty in utilizing the drug treatment effectively for the patient.
  • risperidone formulations formulated in film tablet form dissolve rapidly and homogenously in body and therefore an efficient treatment is provided since absorption and bioavailability of the drug are high in the case that they comprise a composition which is composed of at least two different diluting agents as the diluent and in the case that the first diluting agent composing this composition is selected from cellulose based excipients and the second diluting agent is selected from monosaccharides or disaccharides.
  • the present invention relates to the pharmaceutical formulations comprising risperidone.
  • risperidone formulations which are formulated in film tablet form dissolve rapidly and homogenously in body and therefore an efficient treatment is provided since absorption and bioavailability of the drug are high in the case that they comprise a composition composed of at least two different diluting agents as the diluent and in the case that the first diluting agent composing this composition is selected from cellulose based excipients and the second diluting agent is selected from monosaccharides or disaccharides.
  • the first aspect of the present invention is risperidone formulations formulated in film tablet form comprising a composition composed of at least two different diluting agents as the diluent wherein the first diluting agent composing this composition is selected from cellulose based excipients and the second diluting agent is selected from monosaccharides or disaccharides.
  • film tablet formulations comprising risperidone and a diluent composition wherein the ratio of the first diluting agen the second diluting agent is in the range of 1 : 1 to 1 : 10 by weight, preferably in the range of 1 :2 to 1 :8 by weight.
  • another aspect of the present invention is film tablet formulations comprising risperidone wherein the ratio of the first diluting agen the second diluting agent is in the range of 1 : 1 to 1 : 10 by weight, preferably in the range of 1 :2 to 1 :8 by weight.
  • the first diluting agent can be selected from a group comprising microcrystalline cellulose, silicated microcrystalline, cellulose acetate, modified cellulose and/or a combination thereof in the formulations of the present invention.
  • microcrystalline cellulose is preferably used as the first diluting agent.
  • the second diluting agent can be selected from a group comprising glucose, fructose, galactose, lactose, maltose, sucrose and a combination thereof in the formulations of the present invention.
  • lactose can be used as the second diluting agent in the present invention.
  • lactose in hydrate form preferably lactose monohydrate can be used as the second diluent.
  • the formulation comprising risperidone, characterized in that the ratio of microcrystalline cellulose:lactose monohydrate is in the range of 1 : 1 to 1 : 10 by weight, preferably in the range of 1 :2 to 1 :8 by weight.
  • the active agent risperidone is used in the range of 0.05-10%, preferably in the range of 0.1-8%, more preferably in the range of 0.5-5% in proportion to total weight of the unit dose amount.
  • Risperidone comprised in the pharmaceutical formulations of the present invention can be in the form of its solvates, hydrates, esters, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or a combination thereof in terms of chemical structure.
  • the diluent composition which is used as the diluent is used in the range of 30-99%, preferably in the range of 40-95%, more preferably in the range of 50-90% in proportion to total weight of the unit dose amount.
  • the excipients in the formulation and amount of use of these excipients in proportion to the active agent affect compressibility, solubility, therefore absorption and bioavailability of the tablets obtained in the tablet formulations comprising risperidone significantly.
  • the ratio of risperidone:diluent composition is in the range of 1 : 10 to 1 :80 by weight, preferably in the range of 1 : 15 to 1 :70 by weight, more preferably in the range of 1 :20 to 1 :65 by weight.
  • film tablet formulations comprising risperidone wherein the ratio of risperidone:diluent composition is in the range of 1 :10 to 1 :80 by weight, preferably in the range of 1 :15 to 1 :70 by weight, more preferably in the range of 1 :20 to 1 :65 by weight.
  • the pharmaceutical formulations of the present invention can comprise at least one pharmaceutically acceptable excipient along with risperidone and diluent composition.
  • the pharmaceutically acceptable excipients that can be used in the formulations of the present invention can be selected from a group comprising lubricant, binder and disintegrant.
  • the disintegrant used in the formulations of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, sodium starch glycolate, carboxymethyl cellulose sodium, microcrystalline cellulose, silicone dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminium silicate, starch or combinations thereof.
  • the binder used in the formulations of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, starch, hypromellose, magnesium aluminium silicate, methylcellulose, povidone.
  • the lubricant used in the formulations of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
  • a substance from the group comprising titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, lecithin or a combination thereof, for instance the substance sold on the market under the trademark Opadry Yellow can be used as the film coating agent in the formulations of the present invention.
  • the formulations prepared according to the present invention can comprise disintegrant in the range of 1-50 %, binder in the range of 1-20%, lubricant in the range of 0.1-5%, the coating agent in the range of 0.5 -5% in proportion to total weight of the unit dose amount.
  • the pharmaceutical formulation of the present invention can be obtained by a method comprising the steps of;
  • the pharmaceutical formulation of the present invention can be used in the treatment of schizophrenia, affective symptoms related to schizophrenia, manic episodes of bipolar disorder and restlessness related to autistic disorder.
  • the granulation solution is prepared by mixing one part of the binder with the solvent in obtaining the formulation that shall be used in the present invention. Risperidone, the other part of the binder and one part of the first diluting agent are mixed and sieved. The rest of the first diluting agent, the second diluting agent and powders comprising the disintegrant are stirred in a mixer. The powder mixture obtained is granulated with the granulation solution. The lubricant is added into this mixture and stirred again. The powder mixture obtained is compressed in tablet form and the tablets are coated with the solution comprising the tablet coating agent.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des formulations pharmaceutiques comprenant de la rispéridone qui doivent être utilisées dans le traitement de la schizophrénie, des symptômes affectifs liés à la schizophrénie, des épisodes maniaques du trouble bipolaire et de l'agitation liée à un trouble autiste.
PCT/TR2012/000231 2011-12-27 2012-12-27 Formulations de rispéridone WO2013100876A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
TR2011/12995 2011-12-27
TR201112995 2011-12-27
TR2012/03833 2012-04-04
TR201203833 2012-04-04

Publications (1)

Publication Number Publication Date
WO2013100876A1 true WO2013100876A1 (fr) 2013-07-04

Family

ID=47747754

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2012/000231 WO2013100876A1 (fr) 2011-12-27 2012-12-27 Formulations de rispéridone

Country Status (1)

Country Link
WO (1) WO2013100876A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107028917A (zh) * 2017-03-30 2017-08-11 武汉华夏理工学院 经胃肠道给药的利培酮速溶和/或速释固体口服膜剂及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0196132A2 (fr) 1985-03-27 1986-10-01 Janssen Pharmaceutica N.V. Dérivés de 1,2-benzisoxazol-3-yle et 1,2-benzisothiazol-3-yle
WO2005123084A1 (fr) * 2004-06-15 2005-12-29 Krka, Tovarna Zdravil, D.D., Novo Mesto Composition pharmaceutique a base de risperidone se desintegrant oralement
EP1985287A2 (fr) * 2007-04-25 2008-10-29 Teva Pharmaceutical Industries Ltd. Complexe d'excipient pharmaceutique
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles
EP2281557A2 (fr) * 2008-04-29 2011-02-09 HanAll Biopharma Co., Ltd. Formulation pharmaceutique contenant un agent bloquant les récepteurs de l'angiotensine ii
US20110053866A1 (en) * 2008-08-12 2011-03-03 Biovail Laboratories International (Barbados) S.R.L. Pharmaceutical compositions

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0196132A2 (fr) 1985-03-27 1986-10-01 Janssen Pharmaceutica N.V. Dérivés de 1,2-benzisoxazol-3-yle et 1,2-benzisothiazol-3-yle
WO2005123084A1 (fr) * 2004-06-15 2005-12-29 Krka, Tovarna Zdravil, D.D., Novo Mesto Composition pharmaceutique a base de risperidone se desintegrant oralement
EP1985287A2 (fr) * 2007-04-25 2008-10-29 Teva Pharmaceutical Industries Ltd. Complexe d'excipient pharmaceutique
WO2009043844A2 (fr) * 2007-10-01 2009-04-09 Laboratorios Lesvi, S.L. Comprimés orodispersibles
EP2281557A2 (fr) * 2008-04-29 2011-02-09 HanAll Biopharma Co., Ltd. Formulation pharmaceutique contenant un agent bloquant les récepteurs de l'angiotensine ii
US20110053866A1 (en) * 2008-08-12 2011-03-03 Biovail Laboratories International (Barbados) S.R.L. Pharmaceutical compositions

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107028917A (zh) * 2017-03-30 2017-08-11 武汉华夏理工学院 经胃肠道给药的利培酮速溶和/或速释固体口服膜剂及其制备方法
CN107028917B (zh) * 2017-03-30 2020-07-17 武汉华夏理工学院 经胃肠道给药的利培酮速溶和/或速释固体口服膜剂及其制备方法

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