WO2005077341A1 - Compositions pharmaceutiques a desintegration orale d'ondansetron - Google Patents

Compositions pharmaceutiques a desintegration orale d'ondansetron Download PDF

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Publication number
WO2005077341A1
WO2005077341A1 PCT/IB2005/000094 IB2005000094W WO2005077341A1 WO 2005077341 A1 WO2005077341 A1 WO 2005077341A1 IB 2005000094 W IB2005000094 W IB 2005000094W WO 2005077341 A1 WO2005077341 A1 WO 2005077341A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
water soluble
pharmaceutically acceptable
mixtures
acceptable excipients
Prior art date
Application number
PCT/IB2005/000094
Other languages
English (en)
Inventor
Kamal Mehta
Rajeev Shanker Mathur
Sanjeev Kumar Sethi
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2005077341A1 publication Critical patent/WO2005077341A1/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
    • A61K9/0012—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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • 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
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing

Definitions

  • the present invention relates to orally disintegrating pharmaceutical compositions comprising ondansetron and processes for the preparation thereof.
  • U.S. Patent Nos. 5,955,488 and 6,063,802 disclose a freeze-dried dosage form of ondansetron for oral administration capable of being rapidly disintegrated in the mouth.
  • the product obtained is characterized by a highly porous microstructure of the soluble supporting agent (i.e. mannitol, glycine, lactose, gelatins, etc) in which the active is homogeneously dispersed.
  • WO 99/47126 discloses a rapidly dispersing tablet prepared by using a water- soluble non-saccharide polymer as a binder together with an active ingredient and humidifying the tablet.
  • EP 1334716 discloses medicinal compositions that quickly disintegrate in the oral cavity. These compositions include two or more of sugar alcohols and/or saccharides and an active ingredient. The difference between the melting points of the two sugar alcohols and/or saccharides is 5°C or greater.
  • EP 914818 teaches a tablet comprising sugar alcohol or saccharide each having an average particle diameter of not more than 30 microns, an active ingredient and a disintegrant selected from the group consisting of crospovidone, croscarmellose sodium, and low substituted hydroxypropyl cellulose.
  • the sugar alcohol or the saccharide is present in the amount of 60-95% by weight of the tablet and the disintegrant is present in the amount of 1 - 10% by weight of the tablet.
  • EP 1203580 discloses a quickly disintegrating solid preparation comprising a saccharide or sugar alcohol with the mean particle diameter of 30 microns to 300 microns, a disintegrating agent and a cellulose compound.
  • 6,656,492 discloses a quick disintegrating tablet that includes a plurality of drug-containing particles. Each particle comprises a bitter tasting drug, a pharmaceutical preparation carrier and a saccharide.
  • WO 95/33446 discloses a non-rupturable, fast-dissolving, taste masking composition providing immediate release of pharmaceutically acceptable active ingredients. The composition comprises a non-rupturable drug matrix comprising a taste masking agent and a pharmaceutically acceptable active ingredient.
  • WO 00/57857 describes a rapidly disintegrating tablet for oral administration comprising a therapeutically effective amount of an active ingredient, spray dried mannitol, crospovidone, citric acid and one or more pharmaceutically acceptable excipients.
  • WO 04/096214 describes a composition for oral administration that disintegrates in the oral cavity within about 60 seconds and masks a bitter taste of ondansetron or a pharmaceutically acceptable salt thereof.
  • the composition includes a therapeutically effective amount of ondansetron or a pharmaceutically acceptable salt thereof and an alkalizing agent.
  • an orally disintegrating pharmaceutical composition may be prepared with ondansetron, a filler and at least one disintegrant.
  • the intragranular and extragranular components both contain one or more fillers.
  • Embodiments of the process may include one or more of the following features.
  • the mixing may be done dry granulation or it may be done wet granulation.
  • the one or more pharmaceutically acceptable excipients may include one or more disintegrants, taste masking agents, binders and lubricants.
  • the one or more water soluble fillers may be present from about 10% to about 90% by weight of the composition.
  • the one or more water soluble fillers may include one or both of saccharides and sugar alcohols.
  • the saccharides may include one or more of lactose, sucrose, glucose and mixtures thereof and the sugar alcohols may include one or more of mannitol, sorbitol, xylitol, maltitol and mixtures thereof.
  • the disintegrant may be present from about 1% to about 15% by weight of the composition.
  • the disintegrant may include one or more of croscarmellose sodium, sodium starch glycolate, crospovidone, sodium carboxymethyl cellulose, hydroxypropyl cellulose and mixtures thereof.
  • the taste masking agent may be present at an amount greater than 7% by weight of the composition.
  • the taste-masking agent includes one or more of magnesium oxide, magnesium carbonate, sodium carbonate, sodium phosphate, sodium citrate, calcium gluconate and mixtures thereof.
  • the lubricant may includes one or more of talc, colloidal silicon dioxide, magnesium stearate, zinc stearate and mixtures thereof.
  • the process includes mixing ondansetron, one or more water soluble fillers and one or more pharmaceutically acceptable excipients to obtain a powder blend.
  • the blend is compacted and sieved to obtain an intragranular component.
  • the intragranular component is mixed with one or more water soluble fillers and one or more pharmaceutically acceptable excipients to obtain a mixture.
  • the mixture is filled into capsules or sachets or is compressed into tablets.
  • an orally disintegrating pharmaceutical composition includes an intragranular portion comprising ondansetron, one or more water soluble fillers and one or more pharmaceutically acceptable excipients; and an extragranular portion comprising one or more water soluble fillers and one or more pharmaceutically acceptable excipients.
  • Embodiments of the pharmaceutical composition may include one or more of the following features.
  • the pharmaceutical composition may include one or more pharmaceutically acceptable excipients comprising disintegrants, taste masking agents, binders and lubricants.
  • the one or more water soluble fillers may be present from about 10% to about 90% by weight of the composition.
  • the one or more water soluble fillers may include one or both of saccharides and sugar alcohols.
  • the saccharides may include one or more of lactose, sucrose, glucose and mixtures thereof and the sugar alcohols may include one or more of mannitol, sorbitol, xylitol, maltitol and mixtures thereof.
  • the disintegrant may be present from about 1% to about 15% by weight of the composition.
  • the disintegrant may include one or more of croscarmellose sodium, sodium starch glycolate, crospovidone, sodium carboxymethyl cellulose, hydroxypropyl cellulose and mixtures thereof.
  • the taste masking agents may be present at an amount greater than 7% by weight of the composition.
  • the taste-masking agents include one or more of magnesium oxide, magnesium carbonate, sodium carbonate, sodium phosphate, sodium citrate, calcium gluconate and mixtures thereof.
  • the lubricants may include one or more of talc, colloidal silicon dioxide, magnesium stearate, zinc stearate and mixtures thereof.
  • a method of treating one or more of emesis, nausea, and vomiting associated with cancer chemotherapy, radiotherapy, and/or that occurring post-operatively in a patient in need thereof includes administering an orally disintegrating pharmaceutical composition including an intragranular portion and an extragranular portion.
  • the intragranular portion includes ondansetron, one or more water soluble fillers and one or more pharmaceutically acceptable excipients.
  • the extragranular portion includes one or more water soluble fillers and one or more pharmaceutically acceptable excipients.
  • the inventors have now developed an orally disintegrating pharmaceutical composition containing ondansetron.
  • the pharmaceutical composition also includes one or more water soluble fillers distributed in an intragranular component and an extragranular component and one or more disintegrants.
  • Orally disintegrating' as used herein refers to the composition, which disperses in water within about 60 seconds or less, preferably within about 30 seconds or less.
  • Ondansetron includes ondansetron, single enantiomers, pharmaceutically acceptable salts, solvates and mixtures thereof.
  • Suitable water soluble fillers include one or more of saccharides and sugar alcohols.
  • the saccharides may include one or more of lactose, sucrose and glucose.
  • the sugar alcohols may include one or more of mannitol, sorbitol, xylitol, maltitol and mixtures thereof.
  • the water soluble filler may be mannitol, particularly spray dried mannitol (e.g. Pearlitol SD 200).
  • the water soluble filler may be present from about 10% to about 90%> w/w.
  • Particularly the amount of water soluble filler may be present from about 30% to about 80% w/w.
  • Suitable disintegrants include one or more of croscarmellose sodium, sodium starch glycolate, crospovidone, sodium carboxymethyl cellulose, hydroxypropyl cellulose and mixtures thereof.
  • the disintegrant may be crospovidone or croscarmellose sodium.
  • the disintegrant may be present from about 1% to about 15% w/w.
  • the amount of disintegrant may be present from about 2% to about 10% w/w.
  • Suitable taste-masking agents include one or more of magnesium oxide, magnesium carbonate, sodium carbonate, sodium phosphate, sodium citrate, calcium gluconate and mixtures thereof.
  • the taste masking agent may be magnesium carbonate.
  • the amount of taste masking agent maybe present from about 1% to about
  • Suitable pharmaceutically acceptable excipients include one or more of flavouring agents, colouring agents, sweetening agents, lubricants/glidants and mixtures thereof.
  • Suitable sweetening agents include one or more of aspartame, saccharin sodium and acesulfam K.
  • Suitable lubricants/glidants include one or more of talc, colloidal silicon dioxide, magnesium stearate and zinc stearate. The amount of lubricants/glidants present maybe from about 0.1% to about 8 % w/w. Particularly, the amount of lubricant/glidant present may be from about 0.5% to about 5% w/w.
  • the orally disintegrating pharmaceutical composition prepared according to the present invention may be in the form of tablets, wafers, granules, sachets and any other suitable oral dosage form.
  • a process for the preparation of an orally disintegrating pharmaceutical composition includes mixing ondansetron, one or more water soluble fillers and one or more disintegrants to form a blend.
  • the blend may optionally include one or more taste-masking agents and one or more pharmaceutically acceptable excipients.
  • the blend is then compacted and sieved to obtain an intragranular component.
  • the intragranular component is then mixed with one or more water soluble fillers, and optionally one or more disintegrants and one or more pharmaceutically acceptable excipients, to obtain a blend.
  • the blend may be filled into a capsule/ sachet or compressed into a tablet.
  • a process for the preparation of orally disintegrating granules which include ondansetron. The process includes mixing ondansetron, one or more fillers and one or more distegrants to form a blend. This blend may also include one or more taste masking agents and one or more pharmaceutically acceptable excipients. The blend is compacted to obtain a slug. The slug is then sieved to obtain orally disintegrating granules.
  • the following non-limiting examples describe the various embodiments of the specification.
  • Crospovidone extragranular
  • mannitol extragranular
  • aspartame saccharin sodium
  • talc colloidal silicon dioxide and flavours were sifted through a 44# mesh screen and mixed with material of step 5 in a non-shear blender.
  • Magnesium s4tearate extragranular was sifted through a 44# mesh screen and mixed with material of step 6 to obtain a final blend.
  • the final blend of step 7 was compressed into tablets using flat beveled tooling.
  • Croscarmellose sodium (extragranular), lactose (extragranular), aspartame, saccharin sodium, talc, colloidal silicon dioxide and flavours were sifted through 44# and mixed with material of step 5 in a non shear blender. 7.
  • Magnesium stearate (extragranular) was sifted tlirough a 44# mesh screen and mixed with the material of step 6 to obtain a final blend.
  • the final blend of step 7 was compressed into tablets using flat beveled tooling. Alternatively, the final blend can also be filled into a sachet.
  • Crospovidone extragranular
  • mannitol extragranular
  • aspartame saccharin sodium
  • talc colloidal silicon dioxide and flavours were sifted through a 44# mesh screen and mixed with material of step 5 in a non-shear blender.
  • Magnesium stearate extragranular was sifted through a 44# mesh screen and mixed with material of step 6 to obtain a final blend.
  • the final blend of step 7 was compressed into tablets using flat beveled tooling.
  • the tablets showed reduced bitterness after oral administration. It was observed that the advantageous process of the present invention effectively masks the bitter taste of ondansetron without addition of a taste-masking agent. However, one or more taste- masking agents may be added. Wlice the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are included within the scope of the present invention.

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  • 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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques à désintégration orale comprenant de l'ondansétron et des procédés de préparation de celles-ci.
PCT/IB2005/000094 2004-01-19 2005-01-17 Compositions pharmaceutiques a desintegration orale d'ondansetron WO2005077341A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN79/DEL/2004 2004-01-19
IN79DE2004 2004-01-19

Publications (1)

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WO2005077341A1 true WO2005077341A1 (fr) 2005-08-25

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007090091A3 (fr) * 2006-01-27 2007-11-22 Eurand Inc Système d'administration de médicaments comprenant des médicaments faiblement basiques et des acides organiques
WO2007090082A3 (fr) * 2006-01-27 2007-12-21 Eurand Inc Système d'administration de médicaments comprenant un agent sélectif, faiblement basique bloquant le 5-ht3 de la sérotonine et des acides organiques
CN101129346B (zh) * 2007-07-23 2010-09-29 重庆康刻尔制药有限公司 盐酸氨溴索口腔崩解片及其制备方法
EP2409688A1 (fr) * 2009-03-16 2012-01-25 Nipro Corporation Comprimé se délitant par voie orale
US8133506B2 (en) 2008-03-12 2012-03-13 Aptalis Pharmatech, Inc. Drug delivery systems comprising weakly basic drugs and organic acids
US20230390286A1 (en) * 2019-11-21 2023-12-07 Pharma Mar, S.A. Method of treating sclc and managing thrombocytopenia

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020001617A1 (en) * 2000-05-26 2002-01-03 Chang-Hyun Lee Rapidly disintegrating tablet and process for the manufacture thereof
WO2003086361A1 (fr) * 2002-04-18 2003-10-23 Dr. Reddy's Laboratories Ltd. Compositions orales solides a dispersion rapide
US6649186B1 (en) * 1996-09-20 2003-11-18 Ethypharm Effervescent granules and methods for their preparation
US20030219480A1 (en) * 1999-12-20 2003-11-27 Fassihi A. Reza Amino acid modulated extended release dosage form

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6649186B1 (en) * 1996-09-20 2003-11-18 Ethypharm Effervescent granules and methods for their preparation
US20030219480A1 (en) * 1999-12-20 2003-11-27 Fassihi A. Reza Amino acid modulated extended release dosage form
US20020001617A1 (en) * 2000-05-26 2002-01-03 Chang-Hyun Lee Rapidly disintegrating tablet and process for the manufacture thereof
WO2003086361A1 (fr) * 2002-04-18 2003-10-23 Dr. Reddy's Laboratories Ltd. Compositions orales solides a dispersion rapide

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007090091A3 (fr) * 2006-01-27 2007-11-22 Eurand Inc Système d'administration de médicaments comprenant des médicaments faiblement basiques et des acides organiques
WO2007090082A3 (fr) * 2006-01-27 2007-12-21 Eurand Inc Système d'administration de médicaments comprenant un agent sélectif, faiblement basique bloquant le 5-ht3 de la sérotonine et des acides organiques
EP2363117A1 (fr) * 2006-01-27 2011-09-07 Eurand, Inc. Système d'administration de médicaments comportant un agent de blocage de sérotonine 5-HT3 sélective faiblement basique et acides organiques
EP2387994A1 (fr) * 2006-01-27 2011-11-23 Eurand, Inc. Systèmes d'administration de médicaments comportant des médicaments faiblement basiques et acides organiques
CN101129346B (zh) * 2007-07-23 2010-09-29 重庆康刻尔制药有限公司 盐酸氨溴索口腔崩解片及其制备方法
US8133506B2 (en) 2008-03-12 2012-03-13 Aptalis Pharmatech, Inc. Drug delivery systems comprising weakly basic drugs and organic acids
EP2409688A1 (fr) * 2009-03-16 2012-01-25 Nipro Corporation Comprimé se délitant par voie orale
EP2409688A4 (fr) * 2009-03-16 2013-06-05 Nipro Corp Comprimé se délitant par voie orale
JP5594285B2 (ja) * 2009-03-16 2014-09-24 ニプロ株式会社 口腔内崩壊錠
US20230390286A1 (en) * 2019-11-21 2023-12-07 Pharma Mar, S.A. Method of treating sclc and managing thrombocytopenia

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