FORM-2 THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE
Specification
(Section 10; rule 13)
A PROCESS FOR MANUFACTURING A CONTROLLED
RELEASE TABLET
EMCURE PHARMACEUTICALS LTD.
of Emcure House, T-184, M.I.D.C, Bhosari, Pune 411 026, Maharashtra, India, an Indian Company
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE NATURE OF THIS INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED:-

This invention relates to a process for manufacturing a controlled release tablet.
Particularly, this invention relates to a process for making a novel drug delivery vehicle that is suitable for delivering drugs via the oral route. The present invention also relates to controlled release systems, and, in particular to improved delivery of controlled release medicaments.
It is known that certain design parameters are critical to proper drug delivery. Typically, they are: (1) delivering the drug to the target tissue; (2) supplying the drug in the correct temporal pattern for a predetermined period of time; and (3) fabricating a delivery system that provides drug in the desired spatial and temporal pattern. Controlled release drug delivery systems are intended to utilize these parameters to achieve the aforementioned advantages when compared to conventional pharmaceutical dosing.
"ControUed-release" is used herein to describe a method and composition for making an active ingredient available to the biological system of a host. Controlled-reieasc includes the use of instantaneous release, delayed release, and sustained release. In the context of this specification and invention the term controlled release is used synonymously with "Instantaneous release" which is defined to mean a composition which is immediately release to the biosystem of the host.

The convenience of administering a single fast acting dose of a medication which releases active ingredients in a controlled fashion over an extended period of time, as opposed to the administration of a number of single doses at regular intervals, has long been recognized in the pharmaceutical arts.
The present invention relates to a buccal cavity disintegrable fast dissolving tablet comprising a pharmacologically active ingredient having an adequate strength and capable of dissolving and disintegrating at a high rate in the buccal cavity and to a method and ^paratus of producing the tablet.
Recently research has been undertaken in the geriatric field ranging from the physiology of aging to the design of drugs and pharmaceutical preparatioiK to daily care and assistance. In the case of geriatric medicine, particularly, buccal dissolution type are claimed to be easy for elderly persons to ingest and excellent in stability.
The buccal dissolution type preparations, melt at the temperature prevailing in the buccal cavity and, therefore considerations of sensory factors such as taste and texture as well as moldability and stability are importmit factors.
Jq)anese Patent Laid-open No. 76420/1977 describes a method of manufacturing a porous tablet which features a high disintegration rate insuring rapid dissolution in the buccal

cavity which comprises placing a magmatic mixture or solution containing 5 to 80% by weight of an inert solvent freezing at a temperature of -SO.degree. C. to 25.degree. C. and the balance of a tablet-forming composition in an inert cooling medium such as liquid nitrogen to caitse solidification, then compressing the resulting granules into tablets at a temperature not higher than the freezing point of the solvent, and finally removing the solvent by freeze-drying or air drying.
Japanese Patent Publication No. 24410/1983 discloses a method of manufacturing a porous tablet with good disintegrability which comprises mixing a tablet-coiKtituting composition with a solvent which is inert to said composition and freezes at a temperature of -SO.degree. to +25.degree. C. (for example, water, cyclohexane or benzene), the proportion of said solvent being 5 to 80% by weight, placing the resulting mixture in an inert cooling medium for solidification, compressing the resulting solid into tablets at a temperature lower than the freezing point of said solvent and evaporating the solvent by freeze-drying or spontaneous drying.
Jq)anese Patent Laid-open No. 15830/1986 discloses an antacid composition having a porous and extra fine crystal structure which comprises an antacid and a base for confectionery comprising a sweetener for confectionery and a plasticizer.

However, from the standpoint of practical utility as buccal preparations, the conventional products described above are not ftdly satisfactory in shelf-life, solubility and the scope of compatible medicament. Also these prior art preparations are prepared by heating and melting the ingredients, so that it is inferior in the scope of compatible medicament and disintegratability of the preparation in Ihe buccal cavity. Also, these medicaments have problems with the water solubility of the active ingredient, mechanical strength of the preparation, and % content of the active ingredient so that it is not satisfactory, either, for administration to patients of advanced age.
Furthermore, a tablet which disintegrates and dissolves quickly is generally weak in mechanical strengtifci. Therefore, it has been considered necessary to develop a preparation which offers practically acceptable disintegration and dissolution speeds in the buccal cavity and, at the same time, possesses a sufficient mechanical strength so that it will not be destroyed in the course of manufacture and subsequent distribution.
A tablet may be desirable as an oral dosage form. Dosage units in the form of tablets are usually prepared by compressing a formulation containing a medicinal substance or drug and other ingredients, such as excipients selected for properties which facilitate production and use of the tablet. There are currently tiffee ksv-ovm basic methods foi i:q;wa:ing tablet gssaiulatwos.

These are wet granulation, dry granulation and direct compression. Both wet and dry granulations involve the formation of an agglomerate for feeding to a die cavity. Direct compression usually involves compressing a powder blend of an active ingredient with suitable excipients.
Wet granulation is an expensive process because it requires many processing steps and involves considerable material handling equipment. Consequently, the process requires both energy and substantial space which should be environmentally controlled.
Generally, free water and high level of heat are inimical to active ingredient Wet granulation procedures involve water and/or heat. Therefore, it is desirable to provide a method for making tablets in the substantial absence of high level of heat and free water in order to enhance the survival of active ingredients incorporated in the tablet.
It is, therefore, an object of the invention to provide a method for preparing an oral ingestible dos^e unit, which quickly disintegrates in the mouth.
One problem associated with the oral administration of drugs is that the drug in the form of a tablet or c^sule is difficult to swdlow. Occasionally there have been accidents where the tablet or tiie csqjsule has stuck in the gullet or went down Hie air

passage. In any event, the tablet or capsule is required to be swallowed with water or other liquid. Further, some biologically active substances can be absorbed directly from the oral, particularly the sub lingual mucosa. In this case advantageously, they enter directly into the systemic circulation there by by passing the first pass hepatic metabolism. There is therefore need for a drug delivery vehicle which will permit complete dissolution of the tablet as soon as the vehicle is placed in the buccal cavity with or without small intake of water or other fluid therewith.
One form of an oral disintegrable tablet Is to make a chewable tablet. However, when controlled-release systems are incoiporated in a chewable tablet, che^iving of the tablet may often rupture the coatings on the active ingredient. This results in unpredictable release rates and delivery to the biosystem of the host. Moreover, when controlled-release components are incorporated in compression tablets, the extremely high pressure required to tablet can be expected to rupture the coatings. Consequently, the compression tablet form of deliver)' is not usable, or extremely tough elastic coatings are required to withstand normal tablet pressures.
Furthermore, when controlled-release active ingredients are incorporated in compression tablets, it may be difficult for many people to swallow such tablets. Furthermore, dissolution of high compression tablets is often small and eixatic, resulting

in localized hot spots of alimentary tract irritation where disintegration and release of the active ingredient finally occurs.
The present invention overcomes the disadvantages of the prior art by offering a simple and inexpensive means of incorporating a controUed-release system in a unit dosage form, which avoids the shortcomings normally associated with unit dosage delivery systems.
It is an object of the present invention to provide a fast dissolving tablet haviag adequate disintegratability and solubility in the buccal cavity and sufficient mechanical strength to resist destruction in the course of manufacture and storage.
It is another object of the invention to provide a method of producing a fast dissolving tablet, by which a tablet having the above-mentioned desirable properties can be produced without requiring complicated production procedures.
It is a further object of the invention to provide a fast dissolving tablet which is easy for elderly persons and children to ingest and is, therefore, practically useful and a method of producing the tablet.
Under the circumstances described above, the invention discloses a method of making a buccal dissolution type

pharmaceutical preparation, that when a pharmacologically active ingredient, is imbedded in a saccharide matrix with a lubricant and is compression-molded at low pressures, there is surprisingly obtained a porous tablet having sufficient mechanical strength resisting destruction in the course of manufacture, storage and distribution and yet enable of disintegrating and dissolving r^idly in the buccal cavity wi&out resort to complex production steps which are usually required, such as heating, melting, dissolving, Jfreezing, and the like and that this tablet is fidly suitable for use as a buccal dissolution type tablet.
The fast dissolving tablet of the present invention can be manufactured by compression-molding a composition comprising a pharmacologically active ingredient, a saccharide matrix and a lubricant into a tablet form.
Said fast dissolving tablet can be suitably utilized as a buccal dissoluble and disintegratable tablet because of its easy solubility and disintegratability in the buccal cavity.
According to this invention there is provided a process for manufacturing a controlled release tablet dispersible substantially in the buccal cavity coiwisting the steps of:

Forming a saccharide matrix by thoroughly admixing a saccharide with a disintegrating agent, loading the saccharide and disintegrating mixture on a fluidized bed processor, continuoxisly heating the loaded material at a temperature between 50 to 60 degrees celsius and top spraying the loaded mixture on the fluidized bed with an aqueoi^ binder solution; drying the mixture on the fluidized bed until the outlet temperature reaches 45 to 50 degrees celsius; cooling the granules and sifting the granules to obtain the saccharide matrix in granules of 20 mesh and below; forming active ingredient granules of a drug by admixing together the drug with a hydrophilic £^ent; dissolving the mixture of drug and hydrophilic agent in a granulating solution; sieving the wet mass through a 10 mesh sieve; drying the sieved mass to obtain active granules; forming a lubricant by admixing together a glidant with a disintegrant, sweetening agent and oral coolant and sieving to obtain particles of 40 mesh or less; admixing together the saccharide matrix with the active ingredient granules and the lubricant to obtain a mixed mass; compressing the mixed mass at pressures below 3 kg/square cm to obtain a dispersible tablet.
Typically, the saccharide is at least one saccharide selected from a group of saccharides containing crystalline mono- and di-saccharide structures, i.e., based on C.sub.5 and C.sub.6 sugar structures including glucose, sucrose, fructose, lactose, maltose, pentose, arbiaose, xylose, ribose, mannose, galactose, sorbose, dextrose and sugar alcohols, such as sorbitol, mannitol, xylitol, maltitol, isomalt, sucraiose and the like and mixtures thereof

and/or polysaccharides. hi accordance with a preferred embodiment of the invention, the saccharide contains mannitol.
Typically, the disintegrating agent is at least one disintegrating agent selected from a group of disintegrating agents consisting of sodium starch glycolate, crosspovidone, Crosscarmilose and polyethylene glycol. Particularly, in accordance with a preferred embodiment of the invention, the disintegrating agent is crosspovidone..
Typically, the ratio of the saccharide to the disintegrating agent in the saccharide matrix ranges from 1: 0.025 to 1: 0.035 by mass of the respective substances.
Typically, the binder solution is an aqueous solution of a saccharide selected from a group of saccharides containing crystalline mono- and di-saccharide structures, i.e., based on C.sub.5 and C.sub.6 sugar structures including glucose, sucrose, fructose, lactose, maltose, pentose, arbinose, xylose, ribose, mannose, galactose, sorbose, dextrose and sugar alcohols, such as sorbitol, mannitol, xylitol, maltitol, isomalt, sucralose and the like and mixtures thereof and/or polysaccharides, polyvinl pyrrolidone.
In accordance with a preferred embodiment of the invention, the binder solution contains maltose.
The active ingredient could be at least one selected from a group of medicinal substance consisting of a drug, therapeutic or

prophylactic materials including those in the following ther^eutic categories: ace-inhibitors; anti-anginal drugs; anti-arrythmia agents; antiasthmatics; anticholesterolemics; anticonvulsante; antidepressants; antidiarrheal preparations; antihistamines; antihypertensives; anti-infectives; anti-inflammatories; antilipid agents; antimaniacs; antinaiKeants; antistroke agents; antithyroid preparations; anabolic drugs; antipar^itics; antipsychotics; antipyretics; antispasmodics; antithrombotics; anxiolytic ^ents; appetite stimulants; ^petite suppressants; beta-blocking agente; bronchodilators; cardiov£^cular agents; cerebral dilators; chelating agents; cholecystekinin antagonists; chemotherapeutic agents; cognition activators; contraceptives; coronary dilators; cough suppressants' decongestants; deodorants; dermatological agente; diabetes agents; diuretics; emolliente; enzymes; erythropoietic drugs; expectorants; fertility agente; fimgicides; gastrointestinal agente; growth regulatoi^; hormone replacement ^ente; hyperglycemic agente; laxatives; migraine treatmente; mineral supplemente; mucolytics; narcotics; neuroleptics; neuromuscular drugs; non-steroidal anti-inflammatories (NSAIDs); nutritional additives; peripheral vasodilators; polypeptides; prostaglandins; psychotropics; renin inhibitors; respiratory stimulante; steroids; stimulante; sympatholytics; thyroid preparations; tranquilizers; uterine relaxante; vaginal preparations; vasoconstrictors; vertigo agente; vitamins; wound healing agents; mineral supplemente, vitamiiK, antecids, analgesics, anti-inflammatory substances, anti histamines, gastrointestinal agente, and mixtures thereof

Accordingly, the active ingredient could be at least one selected
from a group of medicinal substance consisting of
acetaminophen, cetirizine, chlorpheniramine, ibuprofen,
flurbiprofen, naproxen, aspirin, pseudoephedrine,
phenylpropanolamine, acetaminophen, ibuprofen, flurbiprofen,
terfenadine carboxylate, chlorpheniramine maleate,
dextromethorphan, sildenafil citrate, domperidon,
diphenhydramine, famotidine, loperamide, ranitidine, cimetidine, astemizole, terfenadine, terfenadine carboxylate, montelukast, mixtures thereof and pharmaceutically acceptable salts thereof, particularly, cetirizine.
Typically, the air fed to the fluidized bed is filtered and purified by treating it with ultra violet radiation.
Typically, the hydrophillic agent is at least one selected from a group consisting of acacia, gelatin, tragacanth, veegum , xanthan gum, carboxymethyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC) or mixtures thereof, carbopols. The Hydrophillic agent could include, among others, gum arable powder, and pullulan.
Preferably, the ratio of the active ingredient to the hydrophilic agent ranges from 1: 3 to 1: 6 .
Advantageously, the glidant is at least one selected from a group consisting of magnesium stearate, calcium stearate, sodium chloride, zinc stearate, hydrogenated vegetable oils, sterotex,

polyoxyethylene, glyceryl monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, starch, dibasic calcium phosphate, magnesium carbonate, ma^esium oxide, calcium silicate, and silica arogels sodium stearyl fimiarate, adipic acid, light mineral oil with sodium stearyl fumarate, waxy fatty acid esters, such as glyceryl behenate, and mixtures thereof, preferably, magnesium stearate and/or colloidal silicone dioxide.
Advantageously, the disintegrant is at least one selected from a group consisting of sodium starch glycolate, crosspovidone. crosscarmilose, polyethylene glycol, preferably, crosspovidone.
In accordance witii a preferred embodiment of the invention, the ratio of the glidant to the disintegrant ranges from 1: 0.4 to 1: 0.6.
The sweetening agent could be at least one selected from a group consisting of glucose (com syrup), sucrose, maltose, dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-l-l-l,2,3-oxathiazin-4-one-2,2-dioxide, particularly the potassiimi salt (acesulfame-K), and sodium and calcium salts thereof The

artificial sweeteners could include dipotassium glycyrrhizinate, and, thaumatin and so on.
The granulating solution could be or could contain predominately boiled purified water the granulating solution contains predominately a solution of methyl paraben and boiled purified water.
Typically, the Flavors may be chosen from natural and synthetic flavoring Uquids. An illustrative list of such agente includes volatile oils, synthetic flavor oils, flavoring aromatics, oils, liquids, oleoresins or extracts cterived from plants, leaves, flowers, fruits, stenK and combination thereof A non-limiting representative list of examples includes citrus oils such as lemon, orange, gr^e, lime and grapefruit and fruit essences including apple, pear, peach, grq)e, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors. Other useful flavorings include aldehydes and esters such as benzaldehyde (cherry, ahnond), citral, i.e., alphacitral (lemon, lime), neral, i.e., beta-citral (lemon, lime) decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), aldehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6-dimethyloctanal (green fruit), and 2-dodecenal (citrus, man^rin), mixtures thereof and the like.
Typically in the granulating solution contains a polymer such as polyvinyl pyrrolidone, a preservative and purified water or

polymer such as polyvinyl pyrrolidone, a flavouring agent a preservative and purified water. Preferably, the granulating solution is filtered before use.
Further, preferably, the sweetening agent is aspartame and the oral coolant is at least one selected fi^om a group coiwisting of menthol derivatives, peppermint and spearmint.
The dryiag of the sieved mass to obtain active granules can be done in a tray dryer at inlet temperature of 60 to 65 degrees Celsius or in a fluid bed processor.
Typically, the ratio of the active ingredient granules to saccharide matrix ranges fi"om 1:4 to 1: 4.5 and the ratio of the active ingredient granules to lubricant ranges fi^om 1: 0.5 to 1: 0.6 .
In accordance with another aspect of this invention there is provided apparatus for manufacturing a controlled release tablet dispersible substantially in the buccal cavity comprising:
A first mixer for admixing a saccharide witii a disintegrating agent; a fluidized bed processor for loading saccharide and disintegrating agent mixture having means for controlled heating of the loaded mixture; air inlet means for supplying air and spraying means for spraying binder solution on top of the loaded mixture; a firet sifting means for sifting granules obtained from the fluidized bed processor to obtain saccharide granules; a second mixer for

forming a wet mass for active ingredient granules; a 10 mesh sieve for sieving the wet mass; drying means to dry the wet mass; a third mixer means for forming a lubricant; a second sieving means for sieving the lubricant to obtain particles of 40 mesh or less; a fourth mixer means for admixing together the saccharide matrix with the active ingredient granules and die lubricant to obtain a mixed mass; and a compressor means adapted to compress the mixed m^s at pressures below 3 k^sqirare in a die and punch arrangement to obtain a dispersible tablet.
Typically, any of the mixers may be a mixer selected from a group of mixers comprising a planetary mixer, a Hobart mixer; a single or multi mill pulverize mixer; a Tubule mixer, a Stephan mixer and a high or low sheer mixers, ribbon mixer, rapid mixer granulator, mass mixer.

Typically, the drier for drying the wet mass is a tray drier or a fluidized bed processor.
According to a preferred embodiment of the invention the fluidized bed processor is fitted with a ultra violet air purifier downstream for purifying the inlet air.
The invention will now be described with reference to the accompanying drawings, in which figure 1 shows a flow chart of the process in accordance with this invention.
Referring to the drawings, a flow chart of a process for the manufacture of A process for manufacturing a controlled release tablet dispersible substantially in the buccal cavity is indicated generally by the reference numeral 10.
The process 10 includes the steps of forming a saccharide matrix by thoroughly admixing [MEKl] a saccharide SAC with a disintegrating agent DISAG, loading the saccharide and disintegrating mixture on a fluidized bed processor, [FB] continuoiKly heating the loaded material at a temperature between 50 to 60 degrees celsius and top spraying the loaded mixture on the fluidized bed with an aqueous binder solution BIND ; drying the mixture on the fluidized bed until the outlet temperature reaches 45 to 50 degrees celsius; cooling [COOL] the granules and sifting [SIFT] the granules to obtain the saccharide matrix SACMAT in granules of 20 mesh and below.

The process 10 also includes separately forming active ingredient ^anules ACTIVGRAN of a drug by admixing together the drug ACTIV with a hydrophilic agent HYD ; dissolving the mixture [MIX2] of drug and hydrophilic agent in a granulating solution GRANSOL; sieving [SIEVE]the wet mass through a 10 mesh sieve; ^ing [DRY] the sieved mass to obtain active granules ACTIVGRAN.
Concurrently the process 10 also includes the step of forming a lubricant LUB by admixing [MIX3] together a glidant GLID with a disintegrant, DIS sweetening agent S and oral coolant C and F and sieving [SIEVE] to obtain particles of 40 mesh or less of the lubricant LUB.
The process 10 fiirther includes the istep of admixing [MIX4] together the saccharide matrix SACMAT with the active ingredient granules ACTIVGRAN and the lubricant LUB to obtain a mixed mass compressing [COMPRESS] the mixed mass at pressures below 3 kg/square cm to obtain a dispersible tablet TAB.
The pharmacologically active ingredient for use in the present invention may be in any optional form, for example, a solid, particulate, granular, crystalline, or oily or solution form. The active ingredient may be at least one member selected from the group consisting of nourishing and health-promoting agents,

antipyretic-analgesic-inflammatory agents, antipsychotic drugs, antianxiety drugs, antidepressants, hypnotic-sedative agents, spasmolytics, gastrointestinal function conditioning agents, antacids, antitussive-expectorants, dental buccal drugs, antihistamines, cardiotonics, antiarrhythmic drugs, diuretics, antihypertensive drugs, vasoconstrictors, coronary vasodilators, peripheral vasodilators, cholagogues, antibiotics, chemotherapeutic drugs, antidiabetic agents, drugs for osteoporosis, skeletal muscle relaxants and so on.
Among said nourishing and health-promoting agents are various vitamins such as vitamin A, vitamin D, vitamin E (d-.alpha.-tocopherol acetate, etc.), vitamin B.sub.l (dibenzoylthiamin, fursultiamine hydrochloride, etc.), vitamin B.sub.2 (riboflavin butyrate, etc.), vitamin B.sub.6 (pyridoxine hydrochloride, etc.), vitamin C (ascorbic acid, sodium L-ascorbate, etc.), vitamin B12 (hydroxocobalamin acetate, etc.); minerals such as calcium, magnesium, iron; proteins; amino acids; oligosaccharides and crude drugs.
The anti asthmatic drugs include salbutamol sulphate .
Among said antipyretic-analgesic-antiinflammatory agents are aspirin, acetaminophen, ethenzamide, ibuprofen, diphenhydramine hydrochloride, dl-chlorpheniramine maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, caffeine, serratiopeptid^e,

lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin, bucolome, pentazocine and so on.
Among said antipsychotic drugs are chlorpromazine, reseipine and so on. The antianxiety drugs include chlordiazepoxide, diazepam and so on. The antidepressants include imipramine, maprotiline, amphetamine and so on. Among said hypnotic-sedatives are estazolam, nitrazepam, diazepam, phenobarbital sodium and so on. The spasmolytics include scopolamine hydrobromide, di¬phenhydramine hydrochloride, p^averine hydrochloride and so on.
The gastrointestinal function conditioning agente include stomachic-digestives such as diastase, saccharated pepsin, scopolia extract, lipase AP, cinnamon oil, etc. and intestinal function controlling drugs such as berberine chloride, resistant lactic acid bacterium, Lactobacillus bifidus and so on.
As said antacids, there may be mentioned magnesium carbonate, sodium hydrogen carbonate, magnesium aluminometasilicate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and so on.
The antitussive-expectorants include chloperastine hydrochloride, dextromethorphan hydrobromide, theophylline, potassium gimiacoisulfonate, guaifenesin and so on. The dental buccal drugs

include oxytetracycline, triamcinolone acetonide, chlorhexidine hydrochloride, lidocaine and so on.
The antihistamines include diphenhydramine hydrochloride, promethazine, isothipendyl hydrochloride, dl-chlorpheniramine maleate, cetirizine and so on.
The cardiotonics include etilefrine hydrochloride and so on. The antiarrhytiimic drugs include procainamide hydrochloride, propranolol hydrochloride, pindolol and so on. The diuretics include isosorbide, furosemide and so on.
The anti emetic anti vertigo drugs include domperidone.
The antihypertensive drugs include delapril hydrochloride, captopril, hexamethonium bromide, hydrdazine hydrochloride, labetalol hydrochloride, methyldopa and so on.
The vasoconstrictors include phenylephrine hydrochloride etc. The coronary vasodilators include carbocromen hydrochloride, molsidomine, verapamil hydrochloride and so on. The peripheral vasodilators include cinnarizine and so on.
The cholagogues include dehydrocholic acid, trepibutone and so on.

The antibiotics include cephems, penems and carbapenems such as cefalexin, amoxicillin, pivmecillinam hydrochloride, cefotiam dihydrochloride and so on.
The chemother^eutic drugs include sulfamethizole, thiazosulfone and so on.
The antidiabetic agents include tolbutamide, vogUbose and so on.
The drugs for osteoporosis include ipriflavone and so on. The skeletal muscle relaxants include methocarvamol and so on.
The saccharide for use in the present invention may be any saccharide that is soluble in water and does not adversely affect the active ingredient (for example, decomposition of the active ingredient). Thus, for example, sugar, starch sugars, lactose, honey, sugar alcohols,tetroses, etc. can also be employed. The sugar includes, among others, sucrose, coupling sugar, fiuctoligosaccharides, palatinose and so on. The starch sugars include, among others, glucose, maltose, powdered syrup, starch syrup, isomerized sugar (fiuctose) and so on. The lactose includes, among others, lactose, isomerized lactose (lactulose), reduced lactose (lactitol) and so on. The honey may be any of the various types, which are commonly used as food. The sugar alcohol includes, among others, sorbitol, mannitol, reduced malt syrup (maltitol), reduced starch saccharides, xylitol, reduced palatinose and so on. Tetroses obtainable by fermentation of glucose (e.g.

erythritol) can also be employed. These saccharides can be used independently or in combination. The preferred species of saccharide for purposes of the present invention are mannitol sucrose, glucose, -maltitol, xylitol, erythritol and so on. Mean particle size of the saccharide is miually in the range of 1 to 100 .mu.ni, preferably 20 to 70 .mu.m and more preferably 30 to 50 .mu.m. The proportion of the saccharide in the above composition varies with the type of active ingredient but generally speaking may be about 10 to 90% by weight, preferably about 20 to 85% by weight and, for still better results, about 30 to 80% by weight.
In the case where the proportion of the active ingredient is in the range of 0.1 to 10% by weight in the composition, where tiie dos^e of the active ingredient is small, the proportion of the saccharide in the composition is generally in the range of 30 to 90% by weight, preferably 50 to 85% by weight and more preferably 60 to 85% by weight. As examples of the active ingredient whose dosage is small, there may be mentioned diazepam and the like.
In the case where the proportion of the active ingredient is in the range of 10 to 30% by weight in the composition, where the dosage of the active ingredient is moderate, the proportion of the saccharide in the composition is generally 20 to 90% by weight, preferably 30 to 80% by weight and more preferably 40 to 75% by wei^t. As examples of the active ingredient whose dosage is


moderate, there may be mentioned antipyretic-analgesic-inflammatory agents and the like.
In the case where the proportion of the active ingredient is in the range of 30 to 70% by weight in tbe composition, where the dosage of the active ingredient is large, the proportion of the saccharide in the composition is usually 10 to 70% by weight, preferably 15 to 60% by weight and more preferably 20 to 50% by weight. As examples of the active ingredient whose dosage is large, there may be mentioned vitamin C and the like.
Unless the object of the invention is interfered with, the above-mentioned composition may further contain a variety of additives which are commonly employed in the manufacture of tablets.
The additives mentioned above include, among others, disintegrators, binders, acids, foaming agents, natural and artificial sweeteners, flavorants, lubricants, colorants and so on.
A novel feature of the invention is the use of a fluid bed processor at low temperatures for granulation to foiTQlffie saccharide matnx."^ A fluidized bed granulator, typically a spouted fluidized bed granulator is used. The operation of the fluidized bed granulator includes maintaining a constant superficial velocity of fluidizing air fed to the fluidized bed. Preferably, air making up the fluidized air consists of purified air having a high relative humidity of 80% or greater. The high relative humidity air is supplied by feeding air to

the humidifier prior to feeding fluidized air at the proper relative humidity to fluidized bed granulator. A portion of the high relative humidity air preferably is used to provide a jet air stream as shown in the fluidized bed granulator unit (FB) of FIG. 1 to maintain better circulation of solids in the bed. It has been found that 20-70% of the total air introduced as feed into the fluidized bed should be introduced as the jet air as shown. Nevertheless, the constant superficial velocity of air should be maintained at about 0.8 to 1.4 m/sec, preferably at about 1.1 m/sec in fluidized bed for particle sizes in the range of about 1-3 mm. At velocities below 0.8 m/sec, granulation rate is undesirably slow. At velocities higher than 1.4 m/sec, entraiimient problems affect the stability of the fluidized bed. The preferred velocity will vary directly with the particle size to be produced. The high relative humidity air used as fluidizing air and as jet air is controlled to have 80% or higher relative humidity to reduce the loss of water from the bed while the saccharide matrix is agglomerating. A binder solution is sprayed on the top of the material loaded on the bed and the outlet temperature is controlled.
A novel combination of apparatus for carrying out the process of the invention for manufacturing a controlled release tablet dispersible substantially in the buccal cavity comprises: A first mixer for admixing a saccharide with a disintegrating agent. A fluidized bed processor for loading saccharide and disintegrating agent mixture having means for controlled heating of the loaded mixture; air inlet means for supplying air and spraying means for spraying binder solution on top of the loaded mixture.

A first sifting means for sifting granules obtained from the fluidized bed processor to obtain saccharide granules.
A second mixer for forming a wet mass for active ingredient
granules.
A 10 mesh sieve for sieving the wet mass.
Drying means to dry the wet mass.
A third mixer moans for forming a lubricant.
A second sieving means for sieving the lubricant to obtain particles
of40 mesh or less.
A fourth mixer means for admixing together the saccharide matrix
with the active ingredient granules and the lubricant to obtain a
mixed mass, and
A compressor means adapted to compress the mixed mass at
pressures below 3 kg/square in a die and punch arrangement to
obtain a dispersible t^let.
The mixers may be a mixer selected from a group of mixers comprising a planetary mixer, a Hobart mixer; a single or multi mill pulverizer mixer; a Turbula mixer, a Stephan mixer and a high or low sheer mixers, ribbon mixer, rapid mixer granulator, mass mixer.

The drier for drying the wet mass is a tray drier or a fluidized bed processor. According to a preferred embodiment of the invention the fluidized bed processor is fitted with a ultra violet air purifier downstream for purifying the inlet air.
The fast dissolving tablet thus obtained has a porous structure. The term porous structure' is used herein to mean a tablet having a porosity of generally 20 to 80%jnd_preferably 30 to 70%. This porous tablet is excellent in disintegratability and solubility in the buccal cavity and has a high falling impact strength.
Thus, die tablet of the invention has a buccal solubility (a time to complete dissolution by saliva in the buccal cavity in a healthy adult male) of generally 0.05 to 3.0 minutes and preferably 0.1 to
1.5 minutes, a disintegration time of generally 0.05 to 3.0 minutes
and preferably 0.1 to 1.5 minutes, a hardness (a value measured with tablet hardness tester) of generally 2 to 25 kg and preferably 3 to 20 kg, and a falling impact strength (a degree of destruction when the tablet is dropped from a height of 30 cm on a glass plate) of generally 0 to 70% and preferably 0 to 40%.
Therefore, the instantaneous release tablet of the present invention can be used for the therapy or prophylaxis of various diseases just as the conventional preparations containing the same active ingredient but with an increased ease of ingestion by elderly persons and children and also as safe preparations for general adults. The tablet of the invention further features a long shelf-life.

The fast dissolving tablet of the present invention contains the active ingredient in a proportion of generally about 0.05 to 90% by weight, preferably about 0.1 to 70% by weight, more preferably 0.3 to 60% by weight and the saccharide matrix in a proportion of generally about 10 to 90% by weight, preferably about 20 to 85%
by weight and, for still better results, about 30 to 80% by weight.
In the case where the dosage of the active ingredient is small, the tablet of the iavention contains the active ingredient in a proportion of generally about 0.1 to 10% by weight, and the saccharide in a proportion of generally 30 to 90% by weight, preferably 50 to 85% by weight and more preferably 60 to85% by weight.
In the case where the dosage of the active ingredient is moderate, the tablet of the invention contains the active ingredient in a proportion of generally about 10 to 30%by weight, and the saccharide in a proportion of generally 20 to 90% by weight, preferably 30 to 80% by weight and more preferably 40 to 75% by weight.
In the case where the dosage of the active ingredient is large, the tablet of the invention contains the active ingredient in a proportion of generally about 30 to 70% by weight, and the saccharide in a proportion of generally 10 to 70% by weight, preferably 15 to 60% by weight and more preferably 20 to 50% by wei^t.

The fast dissolving tablet of the invention can be dosed just as the conventional buccal preparations containing the same active ingredient. The dosage of the tablet of the invention varies according to the type of active ingredient and the patient's age, sex and condition, among other factors. For example, in the case where the active ingredient is diazepam, the tablet is generally administered to adults such that a daily dosage of the active ingredient is in the range of about 0.01 to 100 mg, preferably 0.1 to 30 mg, and for still better results, 0.3 to 10 mg once a day or in 2 or 3 divided doses.
Also, when the vitamin C-containing tablet of the invention is administered as a nourishing and health promoting drug, the dosage of the tablet is about 2 to 2000 mg/day and preferably about 100 to 2000 mg/day as vitamin C.
Anecdotal trials conducted with the q)plication of the tablets produced in accordance with the process of this invention show significant improvement in Ihe availability of the active ingredient in the systemic circulation. Where prompt relief is required, ingestion of this tablet and its immediate comestibility has produced encouraging responses from the patient.
The invention will now be described with reference to the accompanying examples, which are merely illustrative and in no way limit the scope of the invention.

Example 1
A saccharide matrix was formed by thoroughly admixing 614.0 gms of mannitol with 20 gms of crosspovidone. 10 gms of aspartame was added to the mixture. The ingredients were introduced into a multimill with impact forward screen in which the ingredients were pulverized . The ingredients were sifted through a sifter of 40 mesh. The ingredients were mixed in a planetary mixer for 30 minutes and the mixture was loaded on a fluidizedbed Processor. A 5% solution of maltose which acts as a binder solution was top sprayed on Ihe mixture loaded in the fluidized bed and heating was continuous until the outlet temperature attained was 60 degrees Celsius. The mixture was fiuther dried under top spraying until the outlet temperature was 50 degrees celsius. The dried mass was removed from the fluidized bed, cooled, and sifted through a 20 mesh sifter to obtain matrix granules.
Cetirizine granules were prepared by admixing together 20.0 gms of the drug with a 100.0 gms of aluminum magnesium silicate [veegum] . The mixture was pulverized and mixed in a planetary mixer . The mixture was sieved through a 40 mesh sieve.; the mixture was granulated with 105 ml of granulatiQg solution containing 10% polyvinyl pyrrolidone. The wet mass was sieved through a 10 mesh sieve and dried in a tray drier for 30 minutes when the inlet temperature of the drier was 65 degrees celsius to obtain active granules.

A lubricant was prepared by admixing together 24.0 gms of
magnesiumstearate with 15.0 gms of crosspovidone; 4.00 gms
of aspartame; 40.0 gms of peppermint flavor and in a
planetary mixer which was rotated at 25 rpm for 10 minutes. The saccharide matrix, the cetirizine granules and the lubricant were mixed to obtain a mixed mass and compressed with the help of a compression machine at a pressures less than 3 kg/square cm to obtain a dispersible tablet. When placed in the mouth under the tongue, the tablet disintegrated completely in 40 seconds and left behind an agreeable taste. -

Example 2
A saccharide matrix was formed by thoroughly admixing 200.0 gms of maimitol and 100 gm of fructose with 25 gms of crosscarmeUose. 15 gms of aspartame was added to tiie mixture. The ingredients were introduced into a multimill with impact forward screen in which the ingredients were pulverized . The ingrediente were sifted through a sifter of 40 mesh. The ingredients were mixed in a planetary mixer for 30 minutes and the mixture was loaded on a fluidized bed Processor. A 5 % solution of sucrose which acts as a binder solution was top sprayed on the mixture loaded in the fluidized bed and heating w^ continuous until the outlet temperature attained was 60 degrees Celsius. The mixture was finther dried under top spraying until the outlet temperature was 50 degrees Celsius. The dried mass was removed from the fluidized bed, cooled, and sifted tihrough a 20 mesh sifter to obtain matrix granules.
Domperidone granules were prepared by admixing together 20.0 gms of the drug wiHi a 50.0 gms of aluminum magnesium silicate [veegum] . The mixture was pulverized and mixed in a planetary mixer . The mixture was sieved through a 40 mesh sieve.; The mixture was granulated with 105 ml of granulating solution containing 5 % polyvinyl pyrrolidone. The wet mass was sieved through a 10 mesh sieve and dried in a tray drier for 30 minutes when the inlet tanperature of the drier was 65 degrees Celsius to obtain active granules.

A lubricant was prepared by admixing together 20.0 gms of magnesium stearate with 25.0 gms of crosspovidone; 4.00 gms of aspartame; 30.0 gms of strawberry flavor & 5 gm of peppermint flavor and mixed in a planetary mixer which was rotated at 25 rpm for 10 minutes. The saccharide matrix, the Domperidone granules and the lubricants were mixed to obtain a mixed mass and compressed with the help of a compression machine at a pressures less than 3 kg/square cm to obtain a dispersible tablet. When placed in the mouth under the tongue, the tablet disintegrated completely in 35 seconds and left behind an agreeable taste.
Example 3
A saccharide matrix was formed by thoroughly admixing 500.0 gms of mannitol with 20 gms of crosspovidone. 15 gms of aspartame was added to the mixture. The ingredients were introduced into a multimill with impact forward screen in which the ingredients were pulverized . The ingredients were sifted throi^ a sifter of 40 mesh. The ingredients were mixed in a planetary mixer for 30 minutes and the mixture was loaded on a fluidizedbed Processor. A 1.0 % solution of maltose which acts as a binder solution was top sprayed on the mixture loaded in the fluidized bed and heating was continuous until the outiet temperature attained was 60 degrees celsius. The mixture was fijrther dried under top spraying until the outiet temperature was 50 degrees celsius. The dried mass was removed from the fluidized

bed, cooled, and sifted through a 20 mesh sifter to obtain matrix granules.
Salbutamol Sulphate granules were prepared by admixing together 10.0 gms of the drug with a 20.0 gms of aluminum magnesium silicate [veegum] . The mixture was pulverized and mixed in a planetary mixer . The mixture was sieved through a 40 mesh sieve.; The mixture was granulated with 50 ml of granulating solution containing 2% polyvinyl pyrrolidone. The wet mass was sieved through a 10 mesh sieve and dried in a tray drier for 30 minutes when the inlet temperature of the drier was 65 degrees Celsius to obtain active granules.
A lubricant was prepared by admixing together 10.0 gms of
magnesiumstearate with 20.0 gms of crosspovidone; 4.00 gms
of aspartame; 10.0 gn^ of peppermint flavor and in a
planetary mixer which was rotated at 25 rpm for 10 minutes. The saccharide matrix, the Salbutamol sulphate granules and the lubricant were mixed to obtain a mixed mass and compressed with the help of a compression maclune at a pressures less than 3 kg/square cm to obtain a dispersible tablet. When placed in the mouth under the tongue, the tablet disintegrated completely in 30 seconds and left behind an agreeable taste.
While considerable emphasis has been placed herein on the steps of the process and the interrelationships between the steps of the preferred embodiments, it will be appreciated that many

embodiments can be made and that many changes can be made in
the preferred embodiments without departing from the principals
of the invention. These and other changes in the preferred
embodiment as well as other embodiments of the invention will be
apparent to those skilled in the art from the disclosure herein,
whereby it is to be distinctly understood that the foregoing
descriptive matter is to be interpreted merely as illustrative of the
invention and not as a limitation. _ _ _ _ , - -

We Claim:
1. A process for manufacturing a controlled release tablet dispersible substantially in the buccal cavity consisting the steps of: forming a saccharide matrix by thoroughly admixing a saccharide with a disintegrating agent, loading the saccharide and disintegrating mixture on a fluidized bed processor, continuously heating the loaded material at a temperature between 50 to 60 degrees celsius and top spraying the loaded mixture on the fluidized bed with an aqueous binder solution; dtydng the mixture on the fluidized bed until the outlet temperature reaches 45 to 50 degrees celsius; cooling the granules and sifting the granules to obtain the saccharide matrix in granules of 20 : ^esb and below, forming active ingreaieni granules of a drug by adiixing together the drug with a hydrophiijc agent; dissolving the mixture of drug and hydrophilic agent in a granulating solution; sieving the wet mass through a 10 mesh sieve; drying the sieved mass to obtain ?cti\'e granules; forming a lubricant by admixing together a glidant widi a disintegrant, sweetening agent and oral coolant arid sieving to obtain particles of 40 mesh or less; admixing together the saccharide ir'?itT'':X ^7i^h the acth^e ir.gredient granules and tiie lubri'/a'-t to cy-^in a mixed rn?;cs; compressing the mixed mass at pressvrm belo v 3 kg/squpse cm to obtain a dispersible tablet.

2. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the saccharide is at least one saccharide selected from a group of saccharides containing crystalline mono- and di-saccharide structures, i.e., based on C.sub.5 and C.sub.6 sugar structures including glucose, sucrose, fructose, lactose, maltose, pentose, arbinose, xylose, ribose, mannose, galactose, sorbose, dextrose and sugar alcohols, such as sorbitol, mannitol, xylitol, maltitol, isomalt, sucralose and the like and mixtures thereof and/or polysaccharides.
3. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the saccharide contains mannitol.
4. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the disintegrating agent is at least one disintegrating agent selected from a group of disintegrating agents consisting of sodium starch glycolate, crosspovidone. Crosscarmilose, polyethylene glycol.

5. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the disintegrating agent is crosspovidone.
6. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the ratio of the saccharide to the disintegrating agent in the saccharide matrix ranges from 1: 0.025 to 1: 0.035 by mass of the respective substances.

7. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the binder solution is an aqueous solution of a saccharide selected from a group of saccharides containing crystalline mono- and di-saccharide structures, i.e., based on C.sub.5 and C.sub.6 sugar structures including glucose, sucrose, fructose, lactose, maltose, pentose, arbinose, xylose, ribose, mannose, galactose, sorbose, dextrose and sugar alcohols, such as sorbitol, mannitol, xylitol, maltitol, isomalt, sucralose and the like and mixtures thereof and/or polysaccharides, polyvinl pyrrolidone.
8. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the binder solution contains maltose.
9. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the active ingredient is at least one selected from a group of medicinal substance consisting of a drug, therapeutic or prophylactic materials including those in the following therapeutic categories: ace-inhibitors; anti-anginal drugs; anti-arrythmia agents; antiasthmatics; anticholesterolemics; anticonvulsants; antidepressants; antidiarrheal preparations; antihistamines; antihypertensives; anti-infectives; anti-inflammatories; antilipid agents; antimaniacs; antinauseants; antistroke agents; antithyroid preparations; anabolic drugs; antiparasitics; antipsychotics; antipyretics; antispasmodics; antithrombotics; anxiolytic agents; appetite stimulants; appetite suppressants; beta-blocking

agents; bronchodilators; cardiovascular agents; cerebral dilators; chelating agents; cholecystekinin antagonists; chemotherapeutic agents; cognition activators; contraceptives; coronary dilators; cough suppressants' decongestants; deodorants; dermatological agents; diabetes agents; diuretics; emollients; enzymes; erythropoietic drugs; expectorants; fertility agents; fungicides; gastrointestinal agents; growth regulators; hormone replacement agents; hyperglycemic agents; laxatives; migraine treatments; mineral supplements; mucolytics; narcotics; neuroleptics; neuromuscular drugs; non¬steroidal anti-inflammatories (NSAIDs); nutritional additives; peripheral vasodilators; polypeptides; prostaglandins; psychotropics; renin inhibitors; respiratory stimulants; steroids; stimulants; sympatholytics; thyroid preparations; tranquilizers; uterine relaxants; vaginal preparations; vasoconstrictors; vertigo agents; vitamins; wound healing agents; mineral supplements, vitamins, antacids, analgesics, anti-inflammatory substances, anti histamines, gastrointestinal agents, and mixtures thereof.
10.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the active ingredient is at least one selected from a group of medicinal substance consisting of acetaminophen, cetirizine, chlorpheniramine, ibuprofen, flurbiprofen, naproxen, aspirin, pseudoephedrine, phenylpropanolamine, acetaminophen, ibuprofen, flurbiprofen, terfenadine carboxylate, chlorpheniramine maleate, dextromethorphan, sildenafil citrate, domperidon,

diphenhydramine, famotidine, loperamide, ranitidine, cimetidine, astemizole, terfenadine, terfenadine carboxylate, montelukast, mixtures thereof and pharmaceutically acceptable salts thereof
U.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the active ingredient is cetirizine.
12.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the air fed to the fluidized bed is filtered and purified.
13.A process for manufacturing a controlled release tablet as claimed in claim 11, in which the air fed to the fluidized bed is treated with ultra violet radiation.
14.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the hydrophillic agent is at least one selected from a group consisting of acacia, gelatin, tragacanth, veegum , xanthan gum, carboxymethyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and hydroxyethyl cellulose (HEC) or mixtures thereof, carbopolF.
15.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the ratio of the active ingredient to the hydrophilic agent ranges from 1: 3 to 1; 6
. J!

16.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the glidant is at least one selected jfrom a group consisting of magnesium stearate, calcium stearate, sodium chloride, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene, glyceryl monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, starch, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, and silica arogels sodium stearyl fumarate, adipic acid, light mineral oil with sodium stearyl fumarate, waxy fatty acid esters, such as glyceryl behenate, and mixtures thereof.
17.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the glidant is magnesiimi stearate.
18.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the glidant is colloidal silicone dioxide.
19.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the ratio of ghdant to the disintegrant ranges from 1: 0.4 to 1: 0.6.
20.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the sweetening agent is at least one selected from a group consisting of glucose (com syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the

sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin: Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-1-1-1,2,3-oxathiazin-4-one-2,2-dioxide, particularly the potassium salt (acesulfame-K), and sodium and calcium salts thereof.
21. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the granulating solution contains predominately boiled purified water.
22.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the granulating solution contains predominately a solution of methyl paraben and boiled purified water.
23.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the granulating solution contains a polymer such as polyvinyl pyrrolidone, a preservative and purified water.
24.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the granulating solution contains a polymer such as polyvinyl pyrrolidone, a flavouring agent a preservative and purified water.
25.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the sweetening agent is aspartame.

26. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the oral coolant is at least one selected from a group consisting of menthol derivatives, peppermint and spearmint.
27.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the drying of the sieved mass to obtain active granules is done in a tray dryer at inlet temperature of 60 to 65
degrees celsius.
28.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the drying the sieved mass to obtain active granules is done in a fluid bed processor.
29.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the granulating solution is filtered before use.
30.A process for manufacturing a controlled release tablet as claimed in claim 1, in which the ratio of the active ingredient granules to saccharide matrix ranges from 1:4 to 1: 5
31. A process for manufacturing a controlled release tablet as claimed in claim 1, in which the ratio of the active ingredient granules to lubricant ranges from 1: 0.4 to 1: 0.6

32.Apparatus for manufacturing a controlled release tablet dispersible substantially in the buccal cavity comprising: A first mixer for admixing a saccharide with a disintegrating agent; a fluidized bed processor for loading saccharide and disintegrating agent mixture having means for controlled heating of the loaded mixture; air inlet means for supplying air and spraying means for spraying binder solution on top of the loaded mixture; a first sifting means for sifting granules obtained from the fluidized bed processor to obtain saccharide granules; a second mixer for forming a wet mass for active ingredient granules; a 10 mesh sieve for sieving the wet mass; drying means to dry the wet mass; a third mixer means for forming a lubricant; a second sieving means for sieving the lubricant to obtain particles of 40 mesh or less; a fourth mixer means for admixing together the saccharide matrix with the active ingredient granules and the lubricant to obtain a mixed mass; and a compressor means adapted to compress the mixed mass at pressures belovv? 3 kg/square in a die and punch arrangemert to obtaii:. a dispersible tablet.
33.Apparatus for manufacturing a controlled release tablet as claimed in claim 39-, in which the first mixer is a mixer selected from a group of mixers comprising a planetar}^' mixer, a Hobart mixer; a single or multi mill pulverizer mixer; a Turbula mixer, a Stephan mixer and a high or low sheer mixers, ribbon mixer, rapid mixer granulator, mass mixer.

34.Apparatus for manufacturing a controlled release tablet as claimed in claim 3% in which the second mixer is a mixer selected from a group of mixers comprising a planetary mixer, a Hobart mixer; a single or multi mill pulverizer mixer; a Turbula mixer, a Stephan mixer and a high or low sheer mixer.
35.Apparatus for manufacturing a controlled release tablet as claimed in claim 3$*, in which the third mixer is a mixer selected from a group of mixers comprising a planetary mixer, a Hobart mixer; a single or multi mill pulverizer mixer; a Turbula mixer, a Stephan mixer and a high or low sheer mixer.
36.Apparatus for manufacturing a controlled release tablet as claimed in claim 3^ in which the fourth mixer is a mixer selected from a group of mixers comprising a planetary mixer, a Hobart mixer; a single or multi mill pulveris^er mixer; a Turbula mixer, a Stephan mixer and a high or low sheer mixer.
37.Apparatus for manufacturing a controlled release tablet as claimed in claim 3% in which the first, second, third and fourth mixers are the same.
38.Apparatus for manufacturing a controlled release tablet as claimed in claim 3% in which the drier for drying the wet mass is a tray drier.
46

39.Apparatus for manufacturing a controlled release tablet as claimed in claim 3% in which the drier for drying the wet mass is a fluidized bed processor.
40.Apparatus for manufacturing a controlled release tablet as claimed in claim 3^ in which the fluidized bed processor is fitted with a ultra violet air purifier upstream for purifying the inlet air.
47
41.A process for manufacturing a controlled release tablet as described herein with reference to the accompanying drawing.