WO2003086361A1 - Rapidly dispersing solid oral compositions - Google Patents

Rapidly dispersing solid oral compositions Download PDF

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Publication number
WO2003086361A1
WO2003086361A1 PCT/IB2002/001272 IB0201272W WO03086361A1 WO 2003086361 A1 WO2003086361 A1 WO 2003086361A1 IB 0201272 W IB0201272 W IB 0201272W WO 03086361 A1 WO03086361 A1 WO 03086361A1
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WO
WIPO (PCT)
Prior art keywords
starch
composition
group
amount
microcrystalline cellulose
Prior art date
Application number
PCT/IB2002/001272
Other languages
French (fr)
Inventor
Muralikrishna Divi
Abhijit Mukund Deshmukh
Vipin Tatyasaheb Dhanorkar
Mailatur Sivaraman Mohan
Original Assignee
Dr. Reddy's Laboratories Ltd.
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.)
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Publication date
Application filed by Dr. Reddy's Laboratories Ltd. filed Critical Dr. Reddy's Laboratories Ltd.
Priority to AU2002255196A priority Critical patent/AU2002255196A1/en
Priority to PCT/IB2002/001272 priority patent/WO2003086361A1/en
Publication of WO2003086361A1 publication Critical patent/WO2003086361A1/en

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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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • 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
    • A61K9/2027—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
    • 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
    • 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
    • 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

Definitions

  • the present invention relates to the rapidly dispersing solid oral composition and process for manufacture of such compositions.
  • Oral administration in the form of a conventional tablet, pill or capsule constitutes the generally preferred route for administration of pharmaceuticals since this route is generally convenient and acceptable to patients.
  • Such compositions may be associated with certain disadvantages, particularly in the treatment of pediatric or geriatric patients, who may dislike or have difficulty in swallowing such compositions, or where administration of a conventional tablet, pill or capsule is not feasible.
  • freeze dried dosage forms due to the inherent fragility, surface undulation, moisture sensitivity and chemical makeup of freeze-dried dosage forms, the application of compression for the purpose of embossing would cause deformation, reduced porosity and hence increased dispersion time, and possibly cracking of the dosage forms.
  • chemical makeup, moisture sensitivity, porosity and surface undulation of freeze dried dosage forms would cause ink to dissolve the dosage forms at the point of contact or to diffuse throughout the dosage forms leading to clarity problems.
  • the said freeze dried products are also generally not suited for packing and handling operations.
  • Yamanouch Pharmaceutical Co. Ltd. has disclosed into WO 99/47126 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.
  • WO 93/12769 discloses a rapidly dispersing tablet prepared by filling a mold with a suspension containing an active ingredient together with agar and sugar; and drying the suspension to remove the solvent at 30°C in a vacuum.
  • these processes suffer from low productivity and uneven product quality.
  • U.S.Pat.No. 3,885,026 discloses porous tablets prepared by adding a volatilizable adjuvant, e.g., urethane urea, ammonium carbonate or naphthalene, to other tablets components; tableting the resulting mixture; and heating the tablets to volatilize the adjuvant.
  • a volatilizable adjuvant e.g., urethane urea, ammonium carbonate or naphthalene
  • a residual amount of the adjuvant in the tablet may generate a deleterious effect on the patient.
  • U.S.Pat.No.4, 134,943 discloses porous tablets prepared by adding a liquid having a freezing temperature in the range of -30 to 25°C to other tablet components; cooling the mixture below the freezing temperature to solidify the liquid; tableting the cooled mixture; and then evaporating the liquid.
  • this process suffers from low productivity.
  • it is an object of the present invention to provide a rapidly dispersing solid oral composition comprising Ondansetron, Olanzapine along with pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture and method of producing such compositions.
  • the invention relates to the rapidly dispersing compositions and method of producing such compositions.
  • the present invention uses substantially simple and cost effective manufacturing technique.
  • the rapidly dispersible tablets prepared by such process has acceptable stability as per ICH guidelines and dispersed within 30 seconds preferably within 10 seconds and more preferably within 5 seconds.
  • the rapidly dispersible compositions obtainable according to the invention, in addition to being dispersed rapidly have the following further advantages: It has substantially good organoleptic characteristics; It is devoid of any need for the cautions and measures required during handling and packaging of the freeze dried formulations;
  • the active ingredient along with one or more pharmaceutical excipients was blended for 5-10 minutes, the powder blend thus obtained was granulated with solution of wetting agent/surfactant in water, the wet mass thus obtained was sieved to obtain granules. The granules after drying were compressed into the tablets. Alternatively the tablets can be prepared using direct compression technique.
  • the present invention therefore provides the rapidly dispersing tablet formulation for oral administration comprising an active ingredient, in the form of its free base or pharmaceutically accepted salts, solvate, enantiomers or mixtures thereof including racemic mixture and one or more pharmaceutically accepted excipients.
  • rapidly dispersing refers to the dosage form which disperses in water within 30 seconds, preferably within 10 seconds and more preferably within 5 seconds or less as per the test specified in United State Pharmacopoeia.
  • pharmaceutically active ingredient refers to any of the drug selected from ondansetron, olanzapine or pharmaceutically accepted salts, solvate, enantiomers or mixtures thereof including racemic mixture.
  • the term "pharmaceutically accepted excipients" as used in this description and in the appended claims comprise binders, dispersing agents, fillers, flavoring agents, sweetening agents, lubricants or glidants and such like.
  • the "dispersing agent” in accordance with the present invention comprises crosscarmellose sodium, crosscarmellose calcium, crosspovidone, sodium starch glycolate, sodium carboxymethyl cellulose, hydroxypropylcellulose, xanthan gum, alginic acid and alginates one or more clays selected from bentonite, hectorite, magnesium aluminium silicate, and such like, preferably the dispersing agent used in the present invention is crosspovidone.
  • the "binders" used in the present invention are selected from gelatin, pregelatinized starch, starch paste, starch DC, starch 1500, acacia, tragacanth, guar gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, glucose, sucrose, sorbitol, polyvinylpyrrolidone plasdone S-630 and such like.
  • the preferred binder of the present invention is pregelatinized starch.
  • Suitable "fillers” as used in this invention are selected from one or more starch derivatives selected from corn starch, potato starch or rice starch; one or more polysaccharides selected from the group consisting of dextrins or maltodextrins, microcrystalline cellulose, powdered cellulose, mixture of microcrystalline cellulose and guar gum, coprocessed blends of microcrystalline cellulose; one or more polyhydric alcohols selected from the group consisting of mannitol, xylitol, sorbitol and such like.
  • the preferred fillers used in this invention are mannitol, microcrystalline cellulose and mixture of microcrystalline cellulose and guar gum.
  • the "surfactant or wetting agent" as used in this specification and in the appended claims is selected from any of polyoxyethylene sorbitan fatty acid esters, e.g., polyoxyethylene 20 sorbitan monolaurate (TWEEN 20), polyoxyethylene (4) sorbitan monolaurate (TWEEN 21), polyoxyethylene 20 sorbitan monopalmitate (TWEEN 40), polyoxyethylene 20 sorbitan monooleate (TWEEN 80); polyoxyethylene alkyl ethers, e.g., polyoxyethylene 4 lauryl ether (BRIJ 30), polyoxyethylene 23 lauryl ether (BRIJ 35), polyoxyethylene 10 oleyl ether (BRIJ 97); and polyoxyethylene glycol esters, e.g., poloxyethylene 8 stearate (MYRJ 45), poloxyethylene 40 stearate (MYRJ 52) or mixtures thereof, or sodium lauryl sulphate and such like.
  • the suitable "lubricants” are talc, magnesium stearate, stearic acid or glyceryl behenate preferably magnesium stearate and suitable glidants includes colloidal silicon dioxide or talc preferably colloidal silicon dioxide.
  • Suitable “sweeteners” include, for example, sugars such as sucrose, lactose and glucose; cyclamate and salts thereof; saccharin and salts thereof; and aspartame.
  • sugars such as sucrose, lactose and glucose
  • cyclamate and salts thereof e.g., aspartame.
  • saccharin and salts thereof e.g., aspartame.
  • sweetener of the rapidly dispersing dosage form of the present invention is aspartame.
  • Suitable flavoring agent include strawberry, cherry, mint and caramel flavouring aids, preferably the flavoring agent of the present invention is strawberry flavour.
  • rapidly dispersing composition wherein the amount of active ingredient is in the range of 1 to 25 mg.
  • the pharmaceutically active ingredient is Ondansetron or a free base, salt, solvate, enantiomer or mixture thereof including racemic mixture
  • the preferred amount is 4, 8, 16 or 24 mg.
  • the pharmaceutically active ingredient is Olanzapine or a free base, salt, solvate, enantiomer or mixture thereof including racemic mixture
  • the preferred amount is 5, 10, 15 or 20 mg.
  • step (1) The powder blend obtained from step (1) was granulated with the solution of sodium lauryl sulphate (ingredient 11) in water to obtain wet mass.
  • step (3) The wet mass of step (2) was passed through mesh # 10 to obtain wet granules.
  • the wet granules were dried at suitable temperature from 40°C-65°C till the LOD (Loss on drying) of the granules was 2% or less.
  • step (3) The dried granules of step (3) were passed through mesh # 30.
  • step (2) The blend obtained from step (1) was granulated with solution of sodium lauryl sulphate (ingredient 6) in water in FBP (fluid bed processor) and dried.
  • Example 9 The similar method as described in example 1 was adopted for the preparation of above mentioned tablets. Example 9.
  • Example 11 The similar method as described in example 4 was adopted for the preparation of above mentioned tablets. Example 11.
  • ingredients 1-6 are passed through mesh # 40 and blended in suitable blender for 5-10 minutes and compressed into tablets using suitable punches.

Abstract

The present invention relates to the rapidly dispersing solid oral compositions comprising Olanzapine or Ondansetron. The present invention further discloses the wet granulation or direct compression method of producing such rapidly dispersing compositions. The pharmaceutically accepted solvate, salts, enantiomers or mixtures thereof including racemic mixture of Olanzapine and Ondansetron are contemplated to be within the scope of the present invention.

Description

RAPIDLY DISPERSING SOLID ORAL COMPOSITIONS
FIELD OF THE INVENTION
The present invention relates to the rapidly dispersing solid oral composition and process for manufacture of such compositions.
DESCRIPTION OF THE RELEVANT ART
Oral administration in the form of a conventional tablet, pill or capsule constitutes the generally preferred route for administration of pharmaceuticals since this route is generally convenient and acceptable to patients. Unfortunately such compositions may be associated with certain disadvantages, particularly in the treatment of pediatric or geriatric patients, who may dislike or have difficulty in swallowing such compositions, or where administration of a conventional tablet, pill or capsule is not feasible.
In case of patients with psychosis and other mental disorders the administration of conventional solid dosage form is not always suitable due to patient compliance. In case of disorders where water intake needs to be limited or patients have reduced tendency to drink water for eg. Nausea, the use of rapidly dispersing tablet is suitable choice as it can be swallowed without water and disintegrates rapidly when it enters stomach.
U.S. Pat. No. 5,955,488 and 6,063,802 discloses that the Ondansetron hydrochloride dihydrate has bitter taste. In order to solve this problem the patents teaches the use of Ondansetron base in the form of freeze dried dosage form for oral administration. However, such freeze dried dosage form suffers from various drawbacks such as moisture sensitivity, inherent fragility and such like. This causes most of the operations like embossing, packing and handling of such product a difficult and cumbersome operation. In particular, it has been determined that, due to the inherent fragility, surface undulation, moisture sensitivity and chemical makeup of freeze-dried dosage forms, the application of compression for the purpose of embossing would cause deformation, reduced porosity and hence increased dispersion time, and possibly cracking of the dosage forms. Similarly, it is believed that the chemical makeup, moisture sensitivity, porosity and surface undulation of freeze dried dosage forms would cause ink to dissolve the dosage forms at the point of contact or to diffuse throughout the dosage forms leading to clarity problems. The said freeze dried products are also generally not suited for packing and handling operations.
There have been commercialized rapidly dispersing tablets prepared by lyophilizing solutions containing various drugs (U.S.Pat.Nos.5,631,023) e.g., Pepcid® RPD (famotidine preparation, Merck). However, these tablets have the disadvantage in that the productivity of the process for the preparation thereof is very low because the process involves the steps of injecting a drug solutions into a pre-formed container, lyophilizing and coating the lyophilized product with an expensive material.
The said lyophilization and freeze dried technologies are substantially expensive and require sophisticated technologies. In order to overcome above disadvantages various alternative technologies has been tried in past.
Instead of lyophilization, Yamanouch Pharmaceutical Co. Ltd. has disclosed into WO 99/47126 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. Further, WO 93/12769 discloses a rapidly dispersing tablet prepared by filling a mold with a suspension containing an active ingredient together with agar and sugar; and drying the suspension to remove the solvent at 30°C in a vacuum. However, these processes suffer from low productivity and uneven product quality.
Cima labs has developed Orasolv technique which is disclosed in U.S.Pat.No. 6,024,981. Among the tablets prepared thereby, Zomig® Rapimelt (zolmitriptan preparation, Astrazeneca) has been commercialized. This tablet contains an effervescent substance but has the problems of incomplete disintegration in the oral cavity and displeasing effect of the effervescent gas generated in the oral cavity.
U.S.Pat.No. 3,885,026 discloses porous tablets prepared by adding a volatilizable adjuvant, e.g., urethane urea, ammonium carbonate or naphthalene, to other tablets components; tableting the resulting mixture; and heating the tablets to volatilize the adjuvant. However, a residual amount of the adjuvant in the tablet may generate a deleterious effect on the patient.
U.S.Pat.No.4, 134,943 discloses porous tablets prepared by adding a liquid having a freezing temperature in the range of -30 to 25°C to other tablet components; cooling the mixture below the freezing temperature to solidify the liquid; tableting the cooled mixture; and then evaporating the liquid. However, this process suffers from low productivity.
Accordingly, it is an object of the present invention to provide a rapidly dispersing solid oral composition comprising Ondansetron, Olanzapine along with pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture and method of producing such compositions.
SUMMARY OF THE INVENTION The invention relates to the rapidly dispersing compositions and method of producing such compositions. The present invention uses substantially simple and cost effective manufacturing technique. The rapidly dispersible tablets prepared by such process has acceptable stability as per ICH guidelines and dispersed within 30 seconds preferably within 10 seconds and more preferably within 5 seconds. The rapidly dispersible compositions obtainable according to the invention, in addition to being dispersed rapidly have the following further advantages: It has substantially good organoleptic characteristics; It is devoid of any need for the cautions and measures required during handling and packaging of the freeze dried formulations;
> It avoids the use of organic solvents which might pose environmental safety problems According to one of the embodiments of the invention the active ingredient along with one or more pharmaceutical excipients was blended for 5-10 minutes, the powder blend thus obtained was granulated with solution of wetting agent/surfactant in water, the wet mass thus obtained was sieved to obtain granules. The granules after drying were compressed into the tablets. Alternatively the tablets can be prepared using direct compression technique.
DETAILED DESCRIPTION OF THE INVENTION
The present invention therefore provides the rapidly dispersing tablet formulation for oral administration comprising an active ingredient, in the form of its free base or pharmaceutically accepted salts, solvate, enantiomers or mixtures thereof including racemic mixture and one or more pharmaceutically accepted excipients.
As used in this description and in the appended claims the word "rapidly dispersing" refers to the dosage form which disperses in water within 30 seconds, preferably within 10 seconds and more preferably within 5 seconds or less as per the test specified in United State Pharmacopoeia.
In the description and in the appended claims the word "pharmaceutically active ingredient" refers to any of the drug selected from ondansetron, olanzapine or pharmaceutically accepted salts, solvate, enantiomers or mixtures thereof including racemic mixture.
The term "pharmaceutically accepted excipients" as used in this description and in the appended claims comprise binders, dispersing agents, fillers, flavoring agents, sweetening agents, lubricants or glidants and such like. The "dispersing agent" in accordance with the present invention comprises crosscarmellose sodium, crosscarmellose calcium, crosspovidone, sodium starch glycolate, sodium carboxymethyl cellulose, hydroxypropylcellulose, xanthan gum, alginic acid and alginates one or more clays selected from bentonite, hectorite, magnesium aluminium silicate, and such like, preferably the dispersing agent used in the present invention is crosspovidone.
The "binders" used in the present invention are selected from gelatin, pregelatinized starch, starch paste, starch DC, starch 1500, acacia, tragacanth, guar gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, glucose, sucrose, sorbitol, polyvinylpyrrolidone plasdone S-630 and such like. The preferred binder of the present invention is pregelatinized starch.
Suitable "fillers" as used in this invention are selected from one or more starch derivatives selected from corn starch, potato starch or rice starch; one or more polysaccharides selected from the group consisting of dextrins or maltodextrins, microcrystalline cellulose, powdered cellulose, mixture of microcrystalline cellulose and guar gum, coprocessed blends of microcrystalline cellulose; one or more polyhydric alcohols selected from the group consisting of mannitol, xylitol, sorbitol and such like. The preferred fillers used in this invention are mannitol, microcrystalline cellulose and mixture of microcrystalline cellulose and guar gum.
The "surfactant or wetting agent" as used in this specification and in the appended claims is selected from any of polyoxyethylene sorbitan fatty acid esters, e.g., polyoxyethylene 20 sorbitan monolaurate (TWEEN 20), polyoxyethylene (4) sorbitan monolaurate (TWEEN 21), polyoxyethylene 20 sorbitan monopalmitate (TWEEN 40), polyoxyethylene 20 sorbitan monooleate (TWEEN 80); polyoxyethylene alkyl ethers, e.g., polyoxyethylene 4 lauryl ether (BRIJ 30), polyoxyethylene 23 lauryl ether (BRIJ 35), polyoxyethylene 10 oleyl ether (BRIJ 97); and polyoxyethylene glycol esters, e.g., poloxyethylene 8 stearate (MYRJ 45), poloxyethylene 40 stearate (MYRJ 52) or mixtures thereof, or sodium lauryl sulphate and such like. The preferred surfactant of the present invention is sodium lauryl sulphate.
The suitable "lubricants" are talc, magnesium stearate, stearic acid or glyceryl behenate preferably magnesium stearate and suitable glidants includes colloidal silicon dioxide or talc preferably colloidal silicon dioxide.
Suitable "sweeteners" include, for example, sugars such as sucrose, lactose and glucose; cyclamate and salts thereof; saccharin and salts thereof; and aspartame. Preferably the sweetener of the rapidly dispersing dosage form of the present invention is aspartame. Suitable flavoring agent include strawberry, cherry, mint and caramel flavouring aids, preferably the flavoring agent of the present invention is strawberry flavour.
Within the above preferred aspects of the invention, rapidly dispersing composition, wherein the amount of active ingredient is in the range of 1 to 25 mg. When the pharmaceutically active ingredient is Ondansetron or a free base, salt, solvate, enantiomer or mixture thereof including racemic mixture, the preferred amount is 4, 8, 16 or 24 mg. When the pharmaceutically active ingredient is Olanzapine or a free base, salt, solvate, enantiomer or mixture thereof including racemic mixture, the preferred amount is 5, 10, 15 or 20 mg.
It is worth to mention that though examples given in the present description are limited to the particular amount of dosage form, it is obvious to those skilled in the art to find out the composition for other dosage forms and substitute the equivalent excipients as described in this specification or with the one know to the industry.
The following examples describe the present invention in detail but does not limit the invention in any way. Example 1.
Ondansetron 4 mg rapidly dispersing tablet:
Figure imgf000007_0001
Preparation method:
1. Ingredients 1 to 4 and half quantity of ingredient 5 were weighed and passed through mesh #60 and blended for 5-10 minutes.
2. The powder blend obtained from step (1) was granulated with the solution of sodium lauryl sulphate (ingredient 11) in water to obtain wet mass.
3. The wet mass of step (2) was passed through mesh # 10 to obtain wet granules. The wet granules were dried at suitable temperature from 40°C-65°C till the LOD (Loss on drying) of the granules was 2% or less.
4. The dried granules of step (3) were passed through mesh # 30.
5. Ingredients 6 to 10, 12 and remaining half the quantity of ingredients 5 were weighed and passed through mesh # 40 and blended with dried granules obtained from step (4) to obtain lubricated blend. 6. The lubricated blend of step (5) was compressed to tablets using suitable punches. Example 2.
Ondansetron 8mg rapidly dispersing tablet:
Figure imgf000008_0001
Procedure: Same as in example 1. Example 3:
Ondansetron 24 mg rapidly dispersing tablet:
Figure imgf000008_0002
Procedure: Same as in example 1. Example 4:
Ondansetron 4 mg rapidly dispersing tablet:
Figure imgf000009_0001
Preparation method:
1. Ingredients 1 to 3 were weighed and passed through mesh #80 and blended for 5 - 10 minutes.
2. The blend obtained from step (1) was granulated with solution of sodium lauryl sulphate (ingredient 6) in water in FBP (fluid bed processor) and dried.
3. After completion of drying process, ingredients 4, 5, and 7 were charged in to the fluid bed processor and mixed for 3 minutes at 30°C, to obtain a lubricated blend. 4. The lubricated blend of step (3) was passed through mesh # 40 and compressed into tablets using suitable punches. Example 5. Ondansetron 8mg rapidly dispersing tablet:
Figure imgf000009_0002
Preparation method: Same as in example 4. Example 6.
Ondansetron 24 mg rapidly dispersing tablet:
Figure imgf000010_0001
Same as in example 4. Example 7.
Olanzapine 5 mg rapidly dispersing tablet:
Figure imgf000010_0002
Preparation method:
The similar method as described in example 1 was adopted for the preparation of above mentioned tablets.
Example 8.
Olanzapine 10 mg rapidly dispersing tablet:
Figure imgf000011_0001
Preparation method:
The similar method as described in example 1 was adopted for the preparation of above mentioned tablets. Example 9.
Olanzapine 20 mg rapidly dispersing tablet:
Figure imgf000012_0001
Preparation method:
The similar method as described in example 1 was adopted for the preparation of above mentioned tablets.
Example 10.
Olanzapine 5 mg rapidly dispersing tablet:
Figure imgf000012_0002
Preparation method:
The similar method as described in example 4 was adopted for the preparation of above mentioned tablets. Example 11.
Olanzapine 10 mg rapidly dispersing tablet:
Figure imgf000013_0001
Preparation method:
The similar method as described in example 4 was adopted for the preparation of above mentioned tablets.
Example 12.
Olanzapine 20 mg rapidly dispersing tablet:
Figure imgf000013_0002
Preparation method:
The similar method as described in example 4 was adopted for the preparation of above mentioned tablets.
It is obvious to those skilled in the art that both the methods of wet granulation and direct compression can be suitably and successfully applied for the preparation of the tablets as per any of the examples 1 to 4. When direct compression method is used for the manufacture of tablets the water and sodium lauryl sulphate is not needed in the formulation which is exemplified by the following example.
Example 13.
Olanzapine/Ondansetron rapidly dispersing tablets:
Figure imgf000014_0001
Preparation procedure:
All the ingredients 1-6 are passed through mesh # 40 and blended in suitable blender for 5-10 minutes and compressed into tablets using suitable punches.
The examples given above are only meant to be explanatory and in no way limit the scope of the present invention. Many variation of the present invention, disclosed in the detailed description, are obvious to those skilled in the art and are contemplated to be within the scope of the present invention.

Claims

WE CLAIM:
1. Rapidly dispersing solid oral composition comprising Ondansetron or a pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture, in an amount of 1 mg to 25 mg, with at least one pharmaceutically accepted excipients selected from the group consisting of an at least one binder in an amount of 2% to 10%, an at least one dispersing agent in an amount of 5% to 15%, an at least one filler in an amount of 50% to 75%o, an at least one glidants or lubricant in an amount of 0.5% to 5% and an at least one sweetener in an amount of 1% to 6%.
2. The composition of claim 1 comprising the binders selected from the group consisting of gelatin, pregelatinized starch, starch paste, starch DC, starch 1500, acacia, tragacanth, guar gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, glucose, sucrose, sorbitol, polyvinylpyrrolidone or plasdone S-630.
3. The composition of claim 1 comprising the dispersing agent selected from the group consisting of crosscarmellose sodium, sodium carboxymethyl cellulose, crosspovidone, sodium starch glycolate, hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum, alginic acid, alginates or bentonite.
4. The composition of claim 1 comprising the fillers selected from the group consisting of one or more starch derivatives selected from corn starch, potato starch or corn starch one or more polysaccharides selected from the group consisting of dextrins, maltodextrin, microcrystalline cellulose, powdered cellulose, mixture of microcrystalline cellulose and guar gum; one or more polyhydric alcohols selected from the group consisting of mannitol, xylitol or sorbitol.
5. The composition of claim 1 comprising the lubricants selected from talc, magnesium stearate, stearic acid or glyceryl behenate.
6. The composition of claim 1 comprising glidants selected from colloidal silicon dioxide or talc.
7. The composition of claim 1 comprising the sweeteners selected from group consisting of sugars such as sucrose, lactose or glucose; cyclamate or salts thereof; saccharin or salts thereof; or aspartame.
8. Rapidly dispersing solid oral pharmaceutical composition comprising ondansetron as free base, microcrystalline cellulose, pregelatinized starch, mannitol, crosspovidone, aspartame, mixture of microcrystalline cellulose and guar gum, sodium lauryl sulphate, colloidal silicon dioxide and magnesium stearate.
9. Rapidly dispersing solid oral pharmaceutical composition comprising Ondansetron as free base, crosspovidone, aspartame, mixture of microcrystalline cellulose and guar gum, sodium lauryl sulphate and magnesium stearate.
10. Rapidly dispersing solid oral composition comprising Olanzapine or a pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture, in an amount of 1 mg to 25 mg, with at least one pharmaceutically accepted excipients selected from the group consisting of an at least one binder in an amount of 2% to 10%, an at least one dispersing agent in an amount of 5% to 15%, an at least one filler in an amount of 50% to 75%), an at least one glidants or lubricant in an amount of 0.5% to 5%> and an at least one sweetener in an amount of 1% to 6%.
11. The composition of claim 10 comprising the binders selected from the group consisting of gelatin, pregelatinized starch, starch paste, starch DC, starch 1500, acacia, tragacanth, guar gum, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, glucose, sucrose, sorbitol, polyvinylpyrrolidone or plasdone S-630.
12. The composition of claim 10 comprising the dispersing agent selected from the group consisting of crosscarmellose sodium, sodium carboxymethyl cellulose, crosspovidone, sodium starch glycolate, hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum, alginic acid, alginates or bentonite.
13. The composition of claim 10 comprising the fillers selected from the group consisting of one or more starch derivatives selected from corn starch, potato starch or rice starch one or more polysaccharides selected from the group consisting of dextrins, maltodextrin, microcrystalline cellulose, powdered cellulose, mixture of microcrystalline cellulose and guar gum; one or more polyhydric alcohols selected from the group consisting of mannitol, xylitol or sorbitol.
14. The composition of claim 10 comprising the lubricants selected from talc, magnesium stearate, stearic acid or glyceryl behenate.
15. The composition of claim 10 comprising glidants selected from colloidal silicon dioxide or talc.
16. The composition of claim 10 comprising the sweeteners selected from group consisting of sugars such as sucrose, lactose or glucose; cyclamate or salts thereof; saccharin or salts thereof; or aspartame.
17. Rapidly dispersing solid oral pharmaceutical composition comprising Olanzapine as free base, microcrystalline cellulose, pregelatinized starch, mannitol, crosspovidone, aspartame, mixture of microcrystalline cellulose and guar gum, sodium lauryl sulphate, colloidal silicon dioxide and magnesium stearate.
18. Rapidly dispersing solid oral pharmaceutical composition comprising Olanzapine as free base, crosspovidone, aspartame, mixture of microcrystalline cellulose and guar gum, sodium lauryl sulphate and magnesium stearate.
PCT/IB2002/001272 2002-04-18 2002-04-18 Rapidly dispersing solid oral compositions WO2003086361A1 (en)

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WO2008005345A3 (en) * 2006-06-29 2008-03-20 Transcept Pharmaceuticals Inc Compositions of 5-ht3 antagonists and dopamine d2 antagonists for treatment of dopamine-associated chronic conditions
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EP2062599A1 (en) * 2006-09-14 2009-05-27 Astellas Pharma Inc. Orally disintegrating tablet and process for production thereof
EP2062599A4 (en) * 2006-09-14 2013-03-27 Astellas Pharma Inc Orally disintegrating tablet and process for production thereof
US9241908B2 (en) 2007-10-16 2016-01-26 Biocon Limited Orally administrable solid pharmaceutical composition and a process thereof
US9226918B2 (en) 2008-12-04 2016-01-05 The Board Of Trustees Of The Leland Stanford Junior University Methods and compositions for treating or preventing narcotic withdrawal symptoms
EP2246046A1 (en) 2009-04-28 2010-11-03 Sanovel Ilac Sanayi ve Ticaret A.S. Orally disintegrating olanzapine tablet
US10456378B2 (en) 2014-06-24 2019-10-29 Taho Pharmaceuticals Ltd. Fast acting orally disintegrating film
US11304933B2 (en) 2014-06-24 2022-04-19 Taho Pharmaceuticals Ltd. Fast acting orally disintegrating film
CN107625740A (en) * 2016-07-18 2018-01-26 北京科信必成医药科技发展有限公司 A kind of Ondansetron is anhydrous to swallow particle
CN110881555A (en) * 2019-11-07 2020-03-17 哈尔滨梵境园生物科技有限公司 Dispersible candy tablet with dual-effect of lowering blood pressure
WO2024041876A1 (en) * 2022-08-25 2024-02-29 Haleon UK IP Limited Toothpaste tablet composition

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