Indian Patents. 230934:"A NOVEL PHARMACEUTICAL COMPOSITION IN THE FORM OF A TABLET CONSISTING OF CETIRIZINE IN A TASTE MASKED FORM"

Title of Invention	"A NOVEL PHARMACEUTICAL COMPOSITION IN THE FORM OF A TABLET CONSISTING OF CETIRIZINE IN A TASTE MASKED FORM"
Abstract	A novel phanuacatical composition in the form of a tablet consisting of Cetirizine in taste masked form admixed with a fast dissolving matrix comprising; sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/ glidants(s) is provided.

Full Text	Background of Invention : The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration. Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity. However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients : a) who are suffering from or nausea and vomitting b) who have an upper gastrointestinal tract diseases e.g., injury in food pipe d) who have undergone upper Gl surgery e) who are prostrate f) who are elderly and have frequent urination problem at night g) who are incapacitated elderly patients e.g., suffering from Parkinson's disease h) who are children i) who are in situation where water is not available All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug. In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel. U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination. The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried. Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets. PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms. Description of Invention : In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.: According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s). The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.' Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a preferred sugar alcohol being mannitol. : Sweetening agents include saccharin and/or aspartame. The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and others as described in prior art (ref. : The Theory and practice of industrial pharmacy, Leon Lachman, et al., Lea & Febiger, USA) The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches. Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used. Electrolytes include agents like sodium chloride and ammonium chloride. The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste. Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like. The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder. The taste masking of the drug may be effected by the processes/techniques mentioned below : 1. Coating of drug particles 2. Embedment of the drug particles in an inert matrix 3. Complexation The taste masking may be achieved by one process alone or a combination of two or more processes may be used. The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below : a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose, hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, cellulose acetate, cellulose acetate phthalate and the like. b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia d) Acrylates like polymethyl methacrylate e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats, beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids f) Macrogols like polyethylene glycol g) Polyethylene oxides h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols i) Surfactants like products of natural or hydrogenated vegetable oils and ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers. In a preferred embodiment of the present invention the following process was used for taste masking of the drug. The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the composition of invention in an amount of from 0.001 to 20% by weight of the weight of active ingredient. It is then dried to obtain a powder which is further mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets. The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested. The invention is illustrated by the following examples Example 1. % w/w Cetirizine Dihydrochloride 2.5 Crosslinked Polyacrylic Acid 10.0 Soy Lecithin . 0.02 Hydrochloric Acid q.s. to adjust pH Mannitol 64.5 Croscarmellose Sodium 3.75 Povidone 0.25 Aspartame 6.25 Magnesium Stearate 0.50 Aerosil 0.73 Sodium Starch Glycollate ' 3.75 Sodium Chloride 3.00 Citric Acid 2.00 Flavour 2.75 Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg • Example 2. % w/w Cetirizine Dihydrochloride 1.0 Mannitol . 73.0 Sorbitol 15.0 Sodium starch glycollate 4.0 Croscarmellose sodium 3.0 Aspartame 2.0 Flavour 1.0 Magnesium stearate , 1.0 Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate, Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were screened through 100 mesh sieve and thoroughly blended. The mixed powders were compressed into tablets using conventional tabletting machine at a hardness of 1.0 to 3.0 Kg. The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients. Background of Invention : The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration. Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity. However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients : a) who are suffering from or nausea and vomitting b) who have an upper gastrointestinal tract diseases e.g., injury in food pipe d) who have undergone upper Gl surgery e) who are prostrate f) who are elderly and have frequent urination problem at night g) who are incapacitated elderly patients e.g., suffering from Parkinson's disease h) who are children i) who are in situation where water is not available All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug. In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel. U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination. The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried. Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets. PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms. Description of Invention : In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.: According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s). The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.' Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a preferred sugar alcohol being mannitol. : Sweetening agents include saccharin and/or aspartame. The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and others as described in prior art (ref. : The Theory and practice of industrial pharmacy, Leon Lachman, et al., Lea & Febiger, USA) The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches. Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used. Electrolytes include agents like sodium chloride and ammonium chloride. The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste. Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like. The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder. The taste masking of the drug may be effected by the processes/techniques mentioned below : 1. Coating of drug particles 2. Embedment of the drug particles in an inert matrix 3. Complexation The taste masking may be achieved by one process alone or a combination of two or more processes may be used. The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below : a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose, hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, cellulose acetate, cellulose acetate phthalate and the like. b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia d) Acrylates like polymethyl methacrylate e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats, beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids f) Macrogols like polyethylene glycol g) Polyethylene oxides h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols i) Surfactants like products of natural or hydrogenated vegetable oils and ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers. In a preferred embodiment of the present invention the following process was used for taste masking of the drug. The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the composition of invention in an amount of from 0.001 to 20% by weight of the weight of active ingredient. It is then dried to obtain a powder which is further mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets. The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested. The invention is illustrated by the following examples Example 1. % w/w Cetirizine Dihydrochloride 2.5 Crosslinked Polyacrylic Acid 10.0 Soy Lecithin . 0.02 Hydrochloric Acid q.s. to adjust pH Mannitol 64.5 Croscarmellose Sodium 3.75 Povidone 0.25 Aspartame 6.25 Magnesium Stearate 0.50 Aerosil 0.73 Sodium Starch Glycollate ' 3.75 Sodium Chloride 3.00 Citric Acid 2.00 Flavour 2.75 Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg • Example 2. % w/w Cetirizine Dihydrochloride 1.0 Mannitol . 73.0 Sorbitol 15.0 Sodium starch glycollate 4.0 Croscarmellose sodium 3.0 Aspartame 2.0 Flavour 1.0 Magnesium stearate , 1.0 Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate, Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were screened through 100 mesh sieve and thoroughly blended. The mixed powders were compressed into tablets using conventional tabletting machine at a hardness of 1.0 to 3.0 Kg. The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients. Background of Invention : The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration. Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity. However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients : a) who are suffering from or nausea and vomitting b) who have an upper gastrointestinal tract diseases e.g., injury in food pipe d) who have undergone upper Gl surgery e) who are prostrate f) who are elderly and have frequent urination problem at night g) who are incapacitated elderly patients e.g., suffering from Parkinson's disease h) who are children i) who are in situation where water is not available All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug. In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel. U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination. The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried. Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets. PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms. Description of Invention : In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.: According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s). The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.' Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a preferred sugar alcohol being mannitol. : Sweetening agents include saccharin and/or aspartame. The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and others as described in prior art (ref. : The Theory and practice of industrial pharmacy, Leon Lachman, et al., Lea & Febiger, USA) The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches. Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used. Electrolytes include agents like sodium chloride and ammonium chloride. The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste. Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like. The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder. The taste masking of the drug may be effected by the processes/techniques mentioned below : 1. Coating of drug particles 2. Embedment of the drug particles in an inert matrix 3. Complexation The taste masking may be achieved by one process alone or a combination of two or more processes may be used. The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below : a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose, hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, cellulose acetate, cellulose acetate phthalate and the like. b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia d) Acrylates like polymethyl methacrylate e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats, beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids f) Macrogols like polyethylene glycol g) Polyethylene oxides h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols i) Surfactants like products of natural or hydrogenated vegetable oils and ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers. In a preferred embodiment of the present invention the following process was used for taste masking of the drug. The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the composition of invention in an amount of from 0.001 to 20% by weight of the weight of active ingredient. It is then dried to obtain a powder which is further mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets. The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested. The invention is illustrated by the following examples Example 1. % w/w Cetirizine Dihydrochloride 2.5 Crosslinked Polyacrylic Acid 10.0 Soy Lecithin . 0.02 Hydrochloric Acid q.s. to adjust pH Mannitol 64.5 Croscarmellose Sodium 3.75 Povidone 0.25 Aspartame 6.25 Magnesium Stearate 0.50 Aerosil 0.73 Sodium Starch Glycollate ' 3.75 Sodium Chloride 3.00 Citric Acid 2.00 Flavour 2.75 Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg • Example 2. % w/w Cetirizine Dihydrochloride 1.0 Mannitol . 73.0 Sorbitol 15.0 Sodium starch glycollate 4.0 Croscarmellose sodium 3.0 Aspartame 2.0 Flavour 1.0 Magnesium stearate , 1.0 Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate, Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were screened through 100 mesh sieve and thoroughly blended. The mixed powders were compressed into tablets using conventional tabletting machine at a hardness of 1.0 to 3.0 Kg. The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients. We Claim : 1. A novel Fast mouth dissolving tablet comprising Cetirizine in taste masked form admixed with a fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s), all as herein described. 2. The Fast mouth dissolving tablet as claimed in claim 1 wherein the sugar alcohol is mannitol. 3. The Fast mouth dissolving tablet as claimed in claim 1 wherein the sugar alcohol is a mixture of mannitol and sorbitol. 4. The Fast mouth dissolving tablet as claimed in claim 1 to 3 wherein the taste masking of Cetirizine is done in a conventional manner as herein described. 5. The Fast mouth dissolving tablet as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine. 6. The Fast mouth dissolving tablet as claimed in claim 5 wherein each tablet contains 10 mg of Cetirizine. 7. A process for the preparation of a novel Fast mouth dissolving tablet as claimed in claim 1 which comprises admixing Cetirizine in taste masked form with a fast dissolving matrix comprising sugar alcohol(s), sweetner(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/ glidant(s), all as herein described and the admixture thus obtained is formed into tablet in a conventional manner. 8. A process as claimed in claim / wherein the sugar alcohol is mannitol. 9. A process as claimed in claim ¥ wherein the sugar alcohol is a mixture of mannitol and sorbitol. 10. A process as claimed in claims wherein taste masking of Cetirizine is done in a conventional manner as herein described. 11. A process as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine. 12. A process as claimed in claims 1 to 5 wherein each tablet contains 10 mg of Cetirizine. 13. A novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein 14. A process for the preparation of a novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein. We Claim : 1. A novel Fast mouth dissolving tablet comprising Cetirizine in taste masked form admixed with a fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s), all as herein described. 2. The Fast mouth dissolving tablet as claimed in claim 1 wherein the sugar alcohol is mannitol. 3. The Fast mouth dissolving tablet as claimed in claim 1 wherein the sugar alcohol is a mixture of mannitol and sorbitol. 4. The Fast mouth dissolving tablet as claimed in claim 1 to 3 wherein the taste masking of Cetirizine is done in a conventional manner as herein described. 5. The Fast mouth dissolving tablet as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine. 6. The Fast mouth dissolving tablet as claimed in claim 5 wherein each tablet contains 10 mg of Cetirizine. 7. A process for the preparation of a novel Fast mouth dissolving tablet as claimed in claim 1 which comprises admixing Cetirizine in taste masked form with a fast dissolving matrix comprising sugar alcohol(s), sweetner(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/ glidant(s), all as herein described and the admixture thus obtained is formed into tablet in a conventional manner. 8. A process as claimed in claim / wherein the sugar alcohol is mannitol. 9. A process as claimed in claim ¥ wherein the sugar alcohol is a mixture of mannitol and sorbitol. 10. A process as claimed in claims wherein taste masking of Cetirizine is done in a conventional manner as herein described. 11. A process as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine. 12. A process as claimed in claims 1 to 5 wherein each tablet contains 10 mg of Cetirizine. 13. A novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein 14. A process for the preparation of a novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein.

Full Text

Background of Invention :
The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration.
Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the
digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity.
However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients :
a) who are suffering from or nausea and vomitting
b) who have an upper gastrointestinal tract diseases e.g., injury in food
pipe

d) who have undergone upper Gl surgery
e) who are prostrate
f) who are elderly and have frequent urination problem at night
g) who are incapacitated elderly patients e.g., suffering from Parkinson's
disease
h) who are children
i) who are in situation where water is not available
All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating
conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug.
In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel.
U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination.
The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel
process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried.
Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets.
PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms.
Description of Invention :
In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.:
According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s).
The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.'
Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a
preferred sugar alcohol being mannitol. :
Sweetening agents include saccharin and/or aspartame.
The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural
gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and
others as described in prior art (ref. : The Theory and practice of industrial
pharmacy, Leon Lachman, et al., Lea & Febiger, USA)
The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches.
Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used.
Electrolytes include agents like sodium chloride and ammonium chloride.
The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste.
Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like.
The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder.
The taste masking of the drug may be effected by the processes/techniques
mentioned below :
1. Coating of drug particles
2. Embedment of the drug particles in an inert matrix
3. Complexation
The taste masking may be achieved by one process alone or a combination of two or more processes may be used.
The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below :
a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose,
hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy
methyl cellulose, cellulose acetate, cellulose acetate phthalate and the
like.
b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates
c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia
d) Acrylates like polymethyl methacrylate
e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats,
beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids
f) Macrogols like polyethylene glycol
g) Polyethylene oxides
h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols
i) Surfactants like products of natural or hydrogenated vegetable oils and
ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides
Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers.
In a preferred embodiment of the present invention the following process was used for taste masking of the drug.
The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong
acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the
composition of invention in an amount of from 0.001 to 20% by weight of the
weight of active ingredient. It is then dried to obtain a powder which is further
mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets.
The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested.
The invention is illustrated by the following examples
Example 1. % w/w
Cetirizine Dihydrochloride 2.5
Crosslinked Polyacrylic Acid 10.0
Soy Lecithin . 0.02
Hydrochloric Acid q.s. to adjust pH
Mannitol 64.5
Croscarmellose Sodium 3.75
Povidone 0.25
Aspartame 6.25
Magnesium Stearate 0.50
Aerosil 0.73
Sodium Starch Glycollate ' 3.75
Sodium Chloride 3.00
Citric Acid 2.00
Flavour 2.75
Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg •

Example 2. % w/w
Cetirizine Dihydrochloride 1.0
Mannitol . 73.0
Sorbitol 15.0
Sodium starch glycollate 4.0
Croscarmellose sodium 3.0
Aspartame 2.0
Flavour 1.0
Magnesium stearate , 1.0
Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate,
Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were
screened through 100 mesh sieve and thoroughly blended. The mixed powders
were compressed into tablets using conventional tabletting machine at a
hardness of 1.0 to 3.0 Kg.
The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients.
Background of Invention :
The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration.
Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the
digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity.
However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients :
a) who are suffering from or nausea and vomitting
b) who have an upper gastrointestinal tract diseases e.g., injury in food
pipe

d) who have undergone upper Gl surgery
e) who are prostrate
f) who are elderly and have frequent urination problem at night
g) who are incapacitated elderly patients e.g., suffering from Parkinson's
disease
h) who are children
i) who are in situation where water is not available
All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating
conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug.
In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel.
U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination.
The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel
process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried.
Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets.
PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms.
Description of Invention :
In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.:
According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s).
The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.'
Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a
preferred sugar alcohol being mannitol. :
Sweetening agents include saccharin and/or aspartame.
The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural
gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and
others as described in prior art (ref. : The Theory and practice of industrial
pharmacy, Leon Lachman, et al., Lea & Febiger, USA)
The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches.
Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used.
Electrolytes include agents like sodium chloride and ammonium chloride.
The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste.
Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like.
The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder.
The taste masking of the drug may be effected by the processes/techniques
mentioned below :
1. Coating of drug particles
2. Embedment of the drug particles in an inert matrix
3. Complexation
The taste masking may be achieved by one process alone or a combination of two or more processes may be used.
The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below :
a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose,
hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy
methyl cellulose, cellulose acetate, cellulose acetate phthalate and the
like.
b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates
c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia
d) Acrylates like polymethyl methacrylate
e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats,
beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids
f) Macrogols like polyethylene glycol
g) Polyethylene oxides
h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols
i) Surfactants like products of natural or hydrogenated vegetable oils and
ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides
Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers.
In a preferred embodiment of the present invention the following process was used for taste masking of the drug.
The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong
acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the
composition of invention in an amount of from 0.001 to 20% by weight of the
weight of active ingredient. It is then dried to obtain a powder which is further
mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets.
The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested.
The invention is illustrated by the following examples
Example 1. % w/w
Cetirizine Dihydrochloride 2.5
Crosslinked Polyacrylic Acid 10.0
Soy Lecithin . 0.02
Hydrochloric Acid q.s. to adjust pH
Mannitol 64.5
Croscarmellose Sodium 3.75
Povidone 0.25
Aspartame 6.25
Magnesium Stearate 0.50
Aerosil 0.73
Sodium Starch Glycollate ' 3.75
Sodium Chloride 3.00
Citric Acid 2.00
Flavour 2.75
Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg •

Example 2. % w/w
Cetirizine Dihydrochloride 1.0
Mannitol . 73.0
Sorbitol 15.0
Sodium starch glycollate 4.0
Croscarmellose sodium 3.0
Aspartame 2.0
Flavour 1.0
Magnesium stearate , 1.0
Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate,
Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were
screened through 100 mesh sieve and thoroughly blended. The mixed powders
were compressed into tablets using conventional tabletting machine at a
hardness of 1.0 to 3.0 Kg.
The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients.
Background of Invention :
The present invention relates to the use of Cetirizine ([2-[4-[(-Chlorophenyl) Phenylmethyl]-1-1piperazinyl] ethoxy] acetic acid) or its dihydrochloride salt as a antihistaminic agent in the form of a fast dissolving buccal tablet. The compound is a long acting antihistamine with some mast-celK stabilizing* activity. It is claimed to have a low potential for drowsiness in usual doses and to be virtually free from antimuscarinic activity (ref: Martindale The Extra Pharmacopoeia, 31st Edition, Ed. James E F Reynolds, Royal Pharmaceutical Society, London 1996). The chemical structure of Cetirizine is : (Figure Removed)Cetirizine dihydrochloride occurs as a fine, white powder and has a very bitter taste. It is commonly available in the form of coated tablets and suspension for oral administration.
Generally, solid pharmaceutical preparations such as tablets/capsules are designed so that after oral administration, they disintegrate or dissolve in the
digestive organs and the active ingredients are absorbed. Such preparations are not meant to disintegrate or dissolve in the oral cavity.
However in certain conditions there is a requirement of fast disintegrating or dissolving tablets which can be administered even without water. Such fast dissolving tablets disperse readily to form a suspension or solution of the drug after mixing with the saliva, which is easily swallowed by patients. These are particularly suitable for children or aged patients who have difficulty to chewing and/or swallowing an intact tablet/capsule. Fast mouth dissolving tablets are also suitable for those patients :
a) who are suffering from or nausea and vomitting
b) who have an upper gastrointestinal tract diseases e.g., injury in food
pipe

d) who have undergone upper Gl surgery
e) who are prostrate
f) who are elderly and have frequent urination problem at night
g) who are incapacitated elderly patients e.g., suffering from Parkinson's
disease
h) who are children
i) who are in situation where water is not available
All the above conditions necessitate solid dosage forms like tablets and capsules should be modified to accommodate above conditions. Formulating
conventional tablet to dispersible tablets and liquid dosage forms does not solve all the problems stated above. Dispersible tablets still require water and lead to gritty suspensions. Such reconstituted dosage forms as well as ready-made suspensions still cannot be given in all the above situations and additionally they pose problems of uniformity of dose and stability of the drug.
In the past various techniques have been reported for producing such fast dissolving tablets, but most of them require the use cf highly specialized manufacturing processes or specialized packaging. The Zydis technology from R.P. Scherer, England, for instance, utilizes freeze-drying of active ingredient with polymer, sugar and other ingredients to make a fast dissolving dosage form. (Manuf. Chemist. Feb., 1990). European Patent Application No. EP 0 839 526 A2 describes the use of a high cost excipient i.e. erythritol in combination with an active ingredient, crystalline Cellulose and disintegrants to prepare fast disintegrating buccal tablets. U.S Pat. No. 5,073,374 discloses a fast dissolving buccal tablet containing an active ingredient, a water soluble sugar such.as sorbitol and a lubricant. U.S. Pat. No. 5,085,876 discloses a surprisingly fast dissolving sweetening agent in combination with caramel.
U.S. Pat. No. 5,466,464 discloses a solid preparation soluble in buccal cavity containing agar in combination with sugars like lactose and/or mahnitol and an active ingredient. The drawback in this preparation is that agar is a natural material susceptible to variability and microbial contamination.
The composition described in U.S. Pat. No. 5,720,974 requires a special "Compression-Molding" process to produce fast dissolving tablet. U.S. Pat. No. 5, 837, 285 discloses fast soluble tablets which are produced by a novel
process which involves the compression shaping of a wet kneaded mass of drug and sugar alcohol. The wet tablets produced are thereafter dried.
Another U.S. Pat. No. 5,869,098 discloses fast dissolving compressed tablets manufactured by using* partially hygroscopic shearform matrices. Such matrices are prepared from sugar carriers using a flash-heat process. Further, U.S. Pat. No. 5,112,616 discloses the use of solid selected from polyethylene glycols and glycerides, which glycerides melt in the range of 25° to 45° C surfactants selected from the groups consisting of nonionic Poly(oxypropylene)Poly (oxyethylene) copolymers, polyoxyethylene polysorbate deravitives and sodium lauryl sulfate to prepare fast dissolving buccal tablets.
PCT application No. WO 93/23017 defines a fast dissolving solid matrix consisting of gelatin , pectin and/or soy fiber protein and one or more amino acids having from about 2 to 12 carbon atoms.
Description of Invention :
In the present invention, the applicants have invented novel compositions for the drug Cetirizine which are surprisingly fast mouth dissolving solid dosage forms having no bitter taste, and are without any unpleasant feel like gritiiness. Such tablets rapidly dissolve/disperse within one minute requiring very little amount of body fluids like saliva to produce paste like suspension of the drug which is ingested. The size of particles in the suspension is usually less than 100 microns. Such compositions are also devoid of any bitter taste. Such compositions can be compressed into tablets having sufficient mechanical strength using conventional tabletting equipment. These tablets also do not require'any special packaging like peel-off blisters and can be packed in normal push-through type blisters.:
According to the invention there is provided a fast dissolving table s: comprising Cetirizine in taste masked form, admixed with a fast dissolving matrix comprsing sugar alcohol(s), sweetener(s), binder(s). super dismtegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and Iubricant(s)/glidant(s).
The tablets normally contain 5 to 10 mg of Cetirizine, the preferred air'ount being 10mg.'
Suitabla sugar alcohols include mannitol, sorbitol, erythritcl. xylitol ane inaltitol, a
preferred sugar alcohol being mannitol. :
Sweetening agents include saccharin and/or aspartame.
The binding agents include starch, polyvinylpyrrolidone, hydroxy propyl methyl cellulose, hydroxy propyl cellulose, carboxy methyl cellulose, acrylates; natural
gums (e.g. xanthan gum, guar gum, acacia, tragacanth); malto dextrins and
others as described in prior art (ref. : The Theory and practice of industrial
pharmacy, Leon Lachman, et al., Lea & Febiger, USA)
The super disintegrants include crosscarmellose sodium, crospovidone, sodium starch glycollate, microcrystalline cellulose and modified starches.
Suitable flavouring agents like menthol, peppermint and/or fruit essences like mango.orange, pineapple, peach, custard apple and the like may be used.
Electrolytes include agents like sodium chloride and ammonium chloride.
The tablets may also contain a suitable acidifying agent like citric acid, malic acid, ascorbic acid, hydrochloric acid and the like. The presence of acidifying agent reduces the drug solubility thereby reducing the bitter taste.
Lubricants or glidants include Magnesium stearate, talc, colloidal silicon dioxide and the like.
The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with water or suitable non aqueous solvents. The granulating fluid may contain the binder.
The taste masking of the drug may be effected by the processes/techniques
mentioned below :
1. Coating of drug particles
2. Embedment of the drug particles in an inert matrix
3. Complexation
The taste masking may be achieved by one process alone or a combination of two or more processes may be used.
The Taste masking by first two processes mentioned above may be done by the use of inert materials as mentioned below :
a) Cellulosic polymers like hydroxy propyl methyl cellulose, methyl cellulose,
hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose, carboxy
methyl cellulose, cellulose acetate, cellulose acetate phthalate and the
like.
b) Natural polymers like chitosan, pectin, lecithin, maltodextrins, alginates
c) Gums like guar gum, locust bean gum, xanthan gum, tragacanth, acacia
d) Acrylates like polymethyl methacrylate
e) Fats and Waxes like emulsifying wax, paraffins, vegetable or animal fats,
beeswax, wool fat, carauba wax, microcrystalline wax and fatty acids
f) Macrogols like polyethylene glycol
g) Polyethylene oxides
h) Vinyl polymers like polyvinyl pyrrolidones, Polyvinyl acetates and alcohols
i) Surfactants like products of natural or hydrogenated vegetable oils and
ethylene glycol, polyoxyethylene - sorbitan - fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene - polyoxypropylene co-polymers, propylene glycol mono- and di- fatty acid esters, transesterification products of natural vegetable oil triglycerides and polyalkylene polyols, mono-, di- and mono/di- glycerides, sorbitan fatty acid esters, monoglycerides
Taste masking by the use of complexation process may be effected by the use of ion-exchange resins like polacrillin potassium, inclusion complexes with cyclodextrins, or specific polymers like carbomers.
In a preferred embodiment of the present invention the following process was used for taste masking of the drug.
The drug is complexed with an ion-exchange resin. The ratio of drug to the ion-exchange resin is preferably between 1:0.5 to 1:5. The ion-exchange resins are selected from the group comprising weak acid cation exchange resin or strong
acid cation exchange resin. Suitable resins include crosslinked polyacrylic polymer, polacrilin potassium, crosslinked poly methacrylic acid, crosslinked polystyrene sulphonate and the like. The complexed drug is further coated or granulated with lecithin of soy or egg origin. Lecithin is suitably present in the
composition of invention in an amount of from 0.001 to 20% by weight of the
weight of active ingredient. It is then dried to obtain a powder which is further
mixed with the fast dissolving matrix comprising sugar alcohol(s), sweetener(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/glidant(s). It is then compressed into tablets.
The fast dissolving tablets of the present invention are placed on the tongue where they absorb water from saliva, disperse to form a pleasant tasting smooth non-gritty paste which is easily ingested.
The invention is illustrated by the following examples
Example 1. % w/w
Cetirizine Dihydrochloride 2.5
Crosslinked Polyacrylic Acid 10.0
Soy Lecithin . 0.02
Hydrochloric Acid q.s. to adjust pH
Mannitol 64.5
Croscarmellose Sodium 3.75
Povidone 0.25
Aspartame 6.25
Magnesium Stearate 0.50
Aerosil 0.73
Sodium Starch Glycollate ' 3.75
Sodium Chloride 3.00
Citric Acid 2.00
Flavour 2.75
Dissolve Cetirizine dihydrochloride in 20 times of its weight of water. Add Crosslinked Polyacrylic Acid in small increments with constant stirring. Adjust pH to 3 with hydrochloric acid. Keep aside for 1 to 6 hours and then decant the water. Wash the sediment with water atleast twice. Dry the sediment at 40° to 50°C. Transfer it to chilled water (2° to 8°C) containing lecithin (0.15%w/w). Stir for 5 to 15 minutes, filter and dry at 40° to 50°C. Pass through sieve of mesh no 60 (BSS). Mix with pre-sifted (through rriesh no. 30 BSS) blend of Mannitol, Croscarmellose Sodium, Povidone, Aspartame, Magnesium Stearate, Aerosil, Sodium Starch Glycollate, Sodium Chloride, Citric Acid and Flavour. Compress into tablets using conventional tabletting machine at a harnness of 1 - 3 Kg •

Example 2. % w/w
Cetirizine Dihydrochloride 1.0
Mannitol . 73.0
Sorbitol 15.0
Sodium starch glycollate 4.0
Croscarmellose sodium 3.0
Aspartame 2.0
Flavour 1.0
Magnesium stearate , 1.0
Cetirizine dihydrochloride, Mafsnitol, Sforbitol, Sodium starch glycollate,
Croscarmellose Sodium, Aspartame, Flavjour and Magnesium Stearate were
screened through 100 mesh sieve and thoroughly blended. The mixed powders
were compressed into tablets using conventional tabletting machine at a
hardness of 1.0 to 3.0 Kg.
The admixture ©f Cetiriziiae and the af®resaid fast dissolving matrix is n@t a mere adTmixture but has pr^i^rties different frena the sum telal ef the pr©]?erties of its said ingredients.

We Claim :
1. A novel Fast mouth dissolving tablet comprising Cetirizine
in taste masked form admixed with a fast dissolving matrix
comprising sugar alcohol(s), sweetener(s), binder(s), super
disintegrant(s), flavouring agent(s), electrolyte(s),
acidifying agent(s) and lubricant(s)/glidant(s), all as
herein described.
2. The Fast mouth dissolving tablet as claimed in claim 1
wherein the sugar alcohol is mannitol.
3. The Fast mouth dissolving tablet as claimed in claim 1
wherein the sugar alcohol is a mixture of mannitol and
sorbitol.
4. The Fast mouth dissolving tablet as claimed in claim 1 to 3
wherein the taste masking of Cetirizine is done in a
conventional manner as herein described.

5. The Fast mouth dissolving tablet as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine.
6. The Fast mouth dissolving tablet as claimed in claim 5 wherein each tablet contains 10 mg of Cetirizine.

7. A process for the preparation of a novel Fast mouth dissolving tablet as claimed in claim 1 which comprises admixing Cetirizine in taste masked form with a fast

dissolving matrix comprising sugar alcohol(s), sweetner(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/ glidant(s), all as herein described and the admixture thus obtained is formed into tablet in a conventional manner.
8. A process as claimed in claim / wherein the sugar alcohol is mannitol.
9. A process as claimed in claim ¥ wherein the sugar alcohol is a mixture of mannitol and sorbitol.

10. A process as claimed in claims wherein taste masking of Cetirizine is done in a conventional manner as herein described.
11. A process as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine.

12. A process as claimed in claims 1 to 5 wherein each tablet contains 10 mg of Cetirizine.

13. A novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein

14. A process for the preparation of a novel Fast mouth
dissolving tablet substantially as herein described and
illustrated in the Examples herein.
We Claim :
1. A novel Fast mouth dissolving tablet comprising Cetirizine
in taste masked form admixed with a fast dissolving matrix
comprising sugar alcohol(s), sweetener(s), binder(s), super
disintegrant(s), flavouring agent(s), electrolyte(s),
acidifying agent(s) and lubricant(s)/glidant(s), all as
herein described.
2. The Fast mouth dissolving tablet as claimed in claim 1
wherein the sugar alcohol is mannitol.
3. The Fast mouth dissolving tablet as claimed in claim 1
wherein the sugar alcohol is a mixture of mannitol and
sorbitol.
4. The Fast mouth dissolving tablet as claimed in claim 1 to 3
wherein the taste masking of Cetirizine is done in a
conventional manner as herein described.

5. The Fast mouth dissolving tablet as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine.
6. The Fast mouth dissolving tablet as claimed in claim 5 wherein each tablet contains 10 mg of Cetirizine.

7. A process for the preparation of a novel Fast mouth dissolving tablet as claimed in claim 1 which comprises admixing Cetirizine in taste masked form with a fast

dissolving matrix comprising sugar alcohol(s), sweetner(s), binder(s), super disintegrant(s), flavouring agent(s), electrolyte(s), acidifying agent(s) and lubricant(s)/ glidant(s), all as herein described and the admixture thus obtained is formed into tablet in a conventional manner.
8. A process as claimed in claim / wherein the sugar alcohol is mannitol.
9. A process as claimed in claim ¥ wherein the sugar alcohol is a mixture of mannitol and sorbitol.

10. A process as claimed in claims wherein taste masking of Cetirizine is done in a conventional manner as herein described.
11. A process as claimed in claims 1 to 4 wherein each tablet contains 5 to 10 mg of Cetirizine.

12. A process as claimed in claims 1 to 5 wherein each tablet contains 10 mg of Cetirizine.

13. A novel Fast mouth dissolving tablet substantially as herein described and illustrated in the Examples herein

14. A process for the preparation of a novel Fast mouth
dissolving tablet substantially as herein described and
illustrated in the Examples herein.

Documents:

674-DEL-1999-Abstract.pdf

674-DEL-1999-Claims.pdf

674-DEL-1999-Correspondence-Others.pdf

674-DEL-1999-Correspondence-PO.pdf

674-DEL-1999-Description (Complete).pdf

674-DEL-1999-Form-1.pdf

674-DEL-1999-Form-13.pdf

674-DEL-1999-Form-19.pdf

674-DEL-1999-Form-2.pdf

674-DEL-1999-Form-3.pdf

674-DEL-1999-Form-4.pdf

674-DEL-1999-Form-5.pdf

674-DEL-1999-GPA.pdf

674-DEL-1999-Petition-137.pdf

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Patent Number

230934

Indian Patent Application Number

674/DEL/1999

PG Journal Number

13/2009

Publication Date

27-Mar-2009

Grant Date

28-Feb-2009

Date of Filing

04-May-1999

Name of Patentee

PANACEA BIOTEC LIMITED

Applicant Address

B-1EXTN. /A-27 MOHAN CO-OPERATIVE INDUSTRIAL ESTATE, MATHURA ROAD, NEW DELHI-110044.

Inventors:

#	Inventor's Name	Inventor's Address
1	MR. RAJESH JAIN	PANACEA BIOTEC LTD., 24, SCHOOL LANE, NEW DELHI-110001
2	DR. AMARJIT SINGH	PANACEA BIOTEC LTD., 24, SCHOOL LANE, NEW DELHI-110001

PCT International Classification Number

A61K 9/46

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA