FIELD OF THE INVENTION
This invention relates to a mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts thereof comprising granules of levocetirizine and magnesium aluminium silicate wherein granules are prepared by wet granulation method.
BACKGROUND OF THE INVENTION
Cetirizine is a second generation HI histamine receptor antagonist. In its racemic form, it generally offers some significant advantages over the first generation antihistaminics. US 4,525,358 discloses levocetirizine and US 5,698,558 discloses use of (-) cetirizine i.e. levocetirizine in treating the symptoms of seasonal and perennial allergic rhinitis in a human. It also discloses that administration levocetirizine can reduce or avoid adverse side effects associated with the use of racemic cetirizine. These side effects include sedation, somnolence, headache, gastrointestinal disturbance, dizziness, nausea, cardiac arrhythmias, and other cardiovascular effects.
Conventional oral dosage forms display poor patient compliance especially in geriatric, pediatric, and seriously ill patients. These patients generally face difficulty in swallowing these dosage forms. Liquid dosage forms such as syrups are suitable for both the aged and children, however they are associated with problems such as accuracy of doses being administered, spillage as well as stains. Also, have drawbacks in terms of physicochemical stability in a solution form.
Therefore, in recent years many technologies are directed to the pharmaceutical dosage forms, which would disintegrate quickly in the mouth and have accuracy of dosage, physicochemical stability, and ease of ingestion.
These dosage forms however require taste masking for bitter tasting drugs such as
levocetirizine.
US 2006/0083786 discloses solid oral dosage form comprising a coating capable of providing taste masking of the levocetirizine or pharmaceutically acceptable salt thereof, wherein coating comprise magnesium aluminium silicate.
We have now developed an alternate formulation of levocetirizine wherein levocetirizine and magnesium aluminium silicate are wet granulated to provide excellent taste masking.
SUMMARY OF THE INVENTION
Hence, the present invention relates to a mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts thereof.
According to one of the aspects, there is provided a mouth dissolving tablet of levocetirizine or its pharmaceutically acceptable salts thereof comprising granules of levocetirizine and magnesium aluminium silicate wherein granules are prepared by wet granulation method.
In another aspect, there is provided a mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts thereof comprising:
i.about 0.25 to 8% w/w of levocetirizine; ii. about 2.5-15% w/w of magnesium aluminium silicate; iii.about 60 to 90 % w/w of sweetener; iv. about 1 to 10% w/w of disintegrant; wherein tablet is prepared by wet granulation method.
In another aspect, there is provided process for the preparation of a mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts thereof comprising steps of:
i. Dissolving levocetirizine in a solvent;
ii. Granulating magnesium aluminium silicate with solution of step i);
iii. Blending granules of step ii) with other pharmaceutically acceptable excipient;
iv. Lubricating blend of step iii);
v. Compressing blend of step iv) into suitable size tablets.
In another aspect, there is provided a method of treatment of seasonal and perennial allergic rhinitis, the method comprising administering to a subject a mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts thereof comprising granules of levocetirizine and magnesium aluminium silicate wherein granules are prepared by wet granulation method.
DETAILED DESCRIPTION
"Levocetirizine" as employed herein means (-) cetirizine or its pharmaceutically acceptable salt, substantially free of its (+) stereoisomer. Levocetirizine may be used in any of the polymorphic forms.
As used herein, the term "pharmaceutically acceptable salts" refers to the salts of the acids and amides such as citrate, succinate, hydrochloride, hydrobromide, and phosphate.
"Mouth dissolving tablet" as used herein means tablets, which are able to disintegrate in the buccal cavity upon contact with saliva by formation of an easy-to-swallow suspension, in less than 60 seconds. The disintegration time corresponds to the time between the moment when the tablet is placed in the buccal cavity in contact with saliva and the moment when the suspension (resulting from the disintegration without chewing of the tablet) is swallowed.
Magnesium aluminium silicate is derived from natural smectite clay and is capable of forming taste masked adsorbate complex with levocetirizine. This adsorbate complex masks typically strong bitter taste of levocetirizine while the composition is in the oral cavity. It is commercially available as 'Veegum' and some of the grades are Veegum F, Veegum HV, Veegum HS, Veegum K, Veegum PRO, Veegum D, Veegum Ultra, Veegum Plus and Veegum T. The concentration of magnesium aluminium silicate may vary from about 1% to about 20%, in particular it may vary from 2.5% to 15% by weight of the total tablet weight.
Wet granulation as used herein means granulation using any of pharmaceutical acceptable solvent such as water, methanol, ethanol, isopropanol, butanol or mixtures thereof. Wet granulation may be carried out in rapid mixer granulator or fluidized bed granulator.
The granules in addition to levocetirizine and magnesium aluminium silicate may comprise additional pharmaceutically acceptable excipient.
The tablet dosage form may further comprise one or more pharmaceutically acceptable excipients. They include binders, disintegrant, sweeteners, diluents, lubricant/glidant, flavoring agent, and coloring agents.
Disintegrants may be selected from starches or modified starches such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate, cross linked sodium carboxymethylcellulose, hydroxypropyl and mixtures thereof.
Sweeteners include acesulfame K, aspartame, mannitol, saccharins such as sodium saccharin, sucralose and cyclamates such as sodium cyclamates.
Specific examples of "binders" include methyl cellulose, hydroxypropyl cellulose, hydroxyl propyl methylcellulose, polyvinylpyrrolidone, gelatin, gum arable, ethyl cellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, carboxymethyl cellulose, sodium alginate, propylene glycol, microcrystalline cellulose or mixtures thereof.
The term "diluents" as used herein includes calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose excipients, fructose, kaolin, lactitol, lactose, mannitol, sorbitol, starch, sucrose and mixtures thereof.
Specific examples of lubricants/glidants include colloidal silicon dioxide, anhydrous silicic acid, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sodium stearyl fumarate and mixtures thereof.
Examples of suitable flavoring agents include, trusil orange flavor, menthol, yellow plum lemon, tutti frutty, aroma, peppermint oil, oil of wintergreen, orange, strawberry, mint, vanilla, cherry or raspberry or mixtures thereof.
Coloring agent may be selected from FDA approved colorants and the examples are Iron oxide yellow, Lake of Tartrazine, Allura red, Lake of Quinoline yellow, Lake of Erythrosine.
According to one of the embodiment, are prepared by a process comprising the steps of:
i. Dissolving levocetirizine in a solvent;
ii. Granulating magnesium aluminium silicate with solution of step i); iii.Sifting and drying granules of step ii);
iv. Blending granules of step iii) with other pharmaceutically acceptable excipient; v. Lubricating blend of step iv);
vi. Compressing blend of step v) into suitable size tablets. According to another embodiment, are prepared by a process comprising the steps of:
i. Blending levocetirizine and magnesium aluminium silicate together;
ii. Granulating blend of step i) with a solvent;
iii. Sifting and drying of granules of step iii);
iv. Blending granules of step iii) with other pharmaceutically acceptable excipient;
v. Lubricating blend of step iv);
vi. Compressing blend of step v) into a suitable tablet. According to another embodiment, are prepared by a process comprising the steps of:
i. Dissolving levocetirizine and pharmaceutically acceptable excipient in a solvent, ii. Granulating magnesium aluminium silicate with solution of step i), ill.Sifting and drying of granules of step ii),
iv. Optionally, blending granules of step iii) with other pharmaceutically acceptable
excipient,
v. Lubricating blend of step iv),
vi. Compressing blend of step v) into suitable size tablets,
EXAMPLES
Example 1

(Example Removed)
Procedure
i. Levocetirizine was dissolved in purified water, ii. Veegum F was granulated with solution of step ii), iii. Granules of step ii) were dried and sifted,
iv. Mannitol, aspartame, crospovidone, colloidal silicon dioxide, menthol, trusil orange flavor were sifted, added to granules of step iii) and blended together,
v. Magnesium stearate was sifted and added to blend of step iv), vi.Lubricated blend is then compressed into suitable size tablet.
Tablets of example 1 were subjected to disintegration test using DSP disintegration apparatus and it was observed that tablet disintegrated in 10 sec.
Taste masking evaluation and dispersion of tablets in mouth was carried on ten healthy volunteers and taste was found to be acceptable and tablets dispersed in mouth in less than 35 sec.

WE CLAIM:
1. A mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salts
thereof comprising granules of levocetirizine and magnesium aluminium silicate
wherein granules are prepared by wet granulation method.
2. The mouth dissolving tablet according to claim 1 wherein wet granulation is carried
using fluidized bed granulator or rapid mixer granulator.
3. The mouth dissolving tablet according to claim 1 wherein magnesium aluminium
silicate is present in an amount of about 1 to 20 %w/w.
4. The mouth dissolving tablet according to claim 1 wherein pharmaceutically
acceptable salts are selected from citrate, succinate, hydrochloride, hydrobromide,
and phosphate.
5. The mouth dissolving tablet according to claim 1 wherein granules or tablets may
further comprise other pharmaceutically acceptable excipient selected from the group
consisting of sweeteners, binders, diluents, disintegrating agent, antioxidants and
coloring agents.
6. The mouth dissolving tablet according to claim 1 wherein tablet comprises:
i. about 0.25 to 8% w/w of levocetirizine or pharmaceutically acceptable salt thereof; ii. about 2.5 to15% w/w of magnesium aluminium silicate; iii. about 60 to 90 % w/w of sweetener; iv. about 1 to 10% w/w of disintegrant.
7. The mouth dissolving tablet according to claim 5 wherein tablet is prepared by a
process comprising the steps of:
i.Dissolving levocetirizine in a solvent,
ii.Granulating magnesium aluminium silicate with solution of step i),
iii. Blending granules of step ii) with other pharmaceutically acceptable excipient,
iv. Lubricating blend of step iii),
v.Compressing blend of step iv) into suitable size tablets.
8. The mouth dissolving tablet according to claim 7 wherein solvent is selected from
group water, ethanol, isopropanol, butanol or mixtures thereof.
9. The mouth dissolving tablet according to claim 1 for the treatment of seasonal and
perennial allergic rhinitis.
10. The mouth dissolving tablet of levocetirizine or pharmaceutically acceptable salt as
described herein.